Characterization of three novel stem rot pathogens and their antagonistic endophytic bacteria associated with Cistanche deserticola.

Cistanche deserticola is a precious Chinese medicinal material with extremely high health care and medicinal value. In recent years, the frequent occurrence of stem rot has led to reduced or even no harvests of C. deserticola. The unstandardized use of farm chemicals in the prevention and control processes has resulted in excessive chemical residues, threatening the fragile desert ecological environment. Therefore, it is urgent to explore safe and efficient prevention and control technologies. Biocontrol agents, with the advantages of safety and environment-friendliness, would be an important idea. The isolation, screening and identification of pathogens and antagonistic endophytic bacteria are always the primary basis. In this study, three novel pathogens causing C. deserticola stem rot were isolated, identified and pathogenicity tested, namely Fusarium solani CPF1, F. proliferatum CPF2, and F. oxysporum CPF3. For the first time, the endophytic bacteria in C. deserticola were isolated and identified, of which 37 strains were obtained. Through dual culture assay, evaluation experiment and tissue culture verification, a biocontrol candidate strain Bacillus atrophaeus CE6 with outstanding control effect on the stem rot was screened out. In the tissue culture system, CE6 showed excellent control effect against F. solani and F. oxysporum, with the control efficacies reaching 97.2% and 95.8%, respectively, indicating its great potential for application in the production. This study is of great significance for the biocontrol of plant stem rot and improvement of the yield and quality of C. deserticola.

Risk factors for herpes zoster: should people with asthma or COPD be vaccinated?

Without vaccination, an estimated 1 in 3 individuals will develop herpes zoster (HZ) in their lifetime. Increased risk of HZ is attributed to impaired cell-mediated immunity, as observed in age-related immunosenescence or in individuals immunocompromised due to disease or immunosuppressive treatments. Most vaccination guidelines recommend HZ vaccination in all adults ≥ 50 years of age, although Shingrix® was recently approved by the U.S. Food and Drug Administration for use in individuals aged ≥ 18 years who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression caused by known disease or therapy, followed by approval by the European Medicines Agency for use in immunocompromised individuals aged ≥ 18 years. Chronic respiratory diseases are also risk factors for HZ. A new meta-analysis reported 24% and 41% increased risks of HZ in those with asthma and chronic obstructive pulmonary disorder (COPD), respectively, compared with healthy controls. Asthma and COPD increase a person's risk of HZ and associated complications at any age and may be further elevated in those receiving inhaled corticosteroids. Despite the increased risks, there is evidence that HZ vaccination uptake in those aged ≥ 50 years with COPD may be lower compared with the age-matched general population, potentially indicating a lack of awareness of HZ risk factors among clinicians and patients. The 2022 Global Initiative for Chronic Lung Disease report recognizes that Centers for Disease Control and Prevention recommended to vaccinate those aged ≥ 50 years against HZ, although health systems should consider the inclusion of all adults with asthma or COPD into their HZ vaccination programs. Further research into HZ vaccine efficacy/effectiveness and safety in younger populations is needed to inform vaccination guidelines.

What is the context? After experiencing chickenpox, the varicella-zoster virus remains in the body and can be reactivated years later in a form called herpes zoster, more commonly known as shingles. Although shingles is more common in people aged ≥ 50 years, it is also more likely to occur in people with immune systems that do not work normally, which may include those with respiratory conditions such as asthma and chronic obstructive pulmonary disorder (COPD). This disease can be prevented by vaccination. Therefore, it is important for doctors to know which patients are at increased risk of shingles and who could be considered for vaccination. What is new? This review is the first to summarize the risk of shingles in people with asthma or COPD, drawing together evidence from across the world. It also evaluates the recommended use of different shingles vaccines in these patients, with a focus on two widely used vaccines: Zostavax® (ZVL) and Shingrix® (RZV). Asthma or COPD can make people more likely to develop shingles and related medical complications, even in younger people. Most guidelines recommend vaccination against this disease for those aged 50 years and above, with some also recommending vaccination in people aged 18­49 years who may be at higher risk of shingles. There is limited information on the benefit of shingles vaccination in those aged ≤ 50 years with asthma or COPD, but their increased risk of developing shingles suggests they may also benefit from inclusion in vaccination programs. What is the impact? The data presented in the review suggest that people with asthma or COPD aged 18­49 years could benefit from shingles vaccination. This group is not currently included in most vaccination guidelines, despite the evidence of increased risk of shingles and its complications. More information is needed on the risks and benefits of vaccinating this group to determine if it would be cost-effective.

Population pharmacokinetic analyses of tacrolimus in non-transplant patients: a systematic review.

BACKGROUND AND OBJECTIVES: Tacrolimus (TAC) has been increasingly used in patients with non-transplant settings. Because of its large between-subject variability, several population pharmacokinetic (PPK) studies have been performed to facilitate individualized therapy. This review summarized published PPK models of TAC in non-transplant patients, aiming to clarify factors affecting PKs of TAC and identify the knowledge gap that may require further research. METHODS: The PubMed, Embase databases, and Cochrane Library, as well as related references, were searched from the time of inception of the databases to February 2023, to identify TAC population pharmacokinetic studies modeled in non-transplant patients using a non-linear mixed-effects modeling approach. RESULTS: Sixteen studies, all from Asian countries (China and Korea), were included in this study. Of these studies, eleven and four were carried out in pediatric and adult patients, respectively. One-compartment models were the commonly used structural models for TAC. The apparent clearance (CL/F) of TAC ranged from 2.05 to 30.9 L·h-1 (median of 14.9 L·h-1). Coadministered medication, genetic factors, and weight were the most common covariates affecting TAC-CL/F, and variability in the apparent volume of distribution (V/F) was largely explained by weight. Coadministration with Wuzhi capsules reduced CL/F by about 19 to 43%. For patients with CYP3A5*1*1 and *1*3 genotypes, the CL/F was 39-149% higher CL/F than patients with CYP3A5*1*1. CONCLUSION: The optimal TAC dosage should be adjusted based on the patient's co-administration, body weight, and genetic information (especially CYP3A5 genotype). Further studies are needed to assess the generalizability of the published models to other ethnic groups. Moreover, external validation should be frequently performed to improve the clinical practicality of the models.

Serum Proteomic Analysis by Nanoflow LC-MS/MS-Based Proteomics in IgA Chronic Kidney Disease.

BACKGROUND: IgA nephropathy (IgAN) is the most frequently occurring primary glomerulonephritis. A lack of specific biomarkers hinders the early diagnosis and treatment of this disease. This study analyzes and validates potential serum biomarkers using mass spectrometry proteomics. METHODS: Global proteomics profiles of serum from 60 patients with IgAN and 43 healthy control subjects were compared to identify significantly changed proteins. These proteins were validated with targeted proteomics using parallel reaction monitoring (PRM) in an independent validation set consisting of samples from 67 different stage IgAN patients and 60 healthy controls. RESULTS: A total of 37 significantly changed proteins were found in the discovery set, among which 18 proteins were identified as potential biomarkers for IgAN through PRM assays in the validation set. Of these 18 proteins, IgGFc-binding protein, MS-A1 light chain variable region, transthyretin, ficolin-3, and myosin-reactive immunoglobulin light chain variable region were up-regulated in different IgAN stages, B cell receptor heavy chain variable region, rheumatoid factor RF-ET6, heavy chain Fab, cryocrystalglobulin CC1 heavy chain variable region, FLJ94213, lumican, and Q68CN4 (uncharacterized protein) were down-regulated in different IgAN stages. These proteins support previous findings that CKD is accompanied by altered immune response. CONCLUSIONS: This study lays the groundwork for additional research using biomarkers to clinically diagnose IgAN. These proteins are potential molecular markers that could help us understand the potential molecular mechanism of IgAN.

Diagnostic Value of Synovial Fluid Biomarkers for Periprosthetic Joint Infection: A Prospective, Double-blind Trial.

BACKGROUND This prospective, double-blind study investigated the clinical diagnostic value of synovial fluid S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9 (S100A9) in periprosthetic joint infection (PJI) and investigated the subtypes of a-defensin that have diagnostic value for PJI. MATERIAL AND METHODS Synovial fluid samples were collected from 82 patients with suspected PJI after total joint arthroplasty. Patients were divided into a PJI group (n=39) and non-PJI group (n=43). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to determine S100A8, S100A9, alpha-defensin, and internal reference standards in synovial fluid. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of S100A8, S100A9, and alpha-defensin for PJI, as well as the diagnostic value in combination with common biomarkers of infection. RESULTS S100A8, 3 variants of S100A9, and 3 alpha-defensins (human neutrophil peptides [HNP]1-3) in synovial fluid were significantly higher in the PJI group than in the non-PJI group (P<0.001). The sensitivity, specificity, and the area under ROC curve (AUC) for diagnosing PJI were 97.4%, 86.0%, and 0.964 (95% CI: 0.929-0.998), respectively, for synovial fluid S100A8; 87.2%, 88.4% and 0.902 (95% CI: 0.823-0.980), respectively, for S100A9; and 89.7%, 83.7%, and 0.933 (95% CI: 0.884-0.982), respectively, for HNP1-3. The diagnostic efficiency was improved when combined with synovial fluid white blood cell count and percentage of polymorphonuclear neutrophils. CONCLUSIONS Synovial fluid S100A8, S100A9, and HNP1-3 have satisfactory diagnostic efficiency for the diagnosis of PJI, which will help clinicians to accurately diagnose PJI.

Risk of, and risk factors for, vasculopathy associated with acute herpes zoster.

OBJECTIVES: We aimed to summarize the known risk of vasculopathy (stroke, myocardial infarction [MI], and transient ischemic attack [TIA]) after herpes zoster (HZ) and the impact of antiviral treatment and vaccination against HZ on the risk of vasculopathy. MATERIALS AND METHODS: A narrative literature review was conducted in PubMed to identify evidence published in the past 15 years that was relevant to the scope of this article. RESULTS: Ten studies reported that HZ was associated with an increased risk of stroke and one UK study reported no association. Four studies reported that HZ was associated with an increased risk of MI, and four reported that HZ was associated with an increased risk of TIA. Two studies reported that antiviral treatment was associated with a reduced risk of stroke and an additional two studies reported no association between antiviral treatment and the risk of stroke. In addition, two studies reported that vaccination against HZ using the live zoster vaccine (ZVL) was associated with a reduced risk of stroke, and an additional two studies reported that the risk of stroke or MI after HZ was similar between ZVL vaccinated and unvaccinated individuals. CONCLUSIONS: HZ is associated with an increased risk of stroke, MI, or TIA (strongest association is between HZ and stroke). Further studies are needed to determine whether antiviral treatment or ZVL vaccination influence the risk of HZ-associated vasculopathy. In addition, the effect of the recombinant zoster vaccine on the risk of HZ-associated vasculopathy should be studied.

Circular RNA circPTPRF promotes the progression of GBM via sponging miR-1208 to up-regulate YY1.

Glioblastoma (GBM) is the most common primary malignant tumor in the brain, and its robust proliferation and invasion abilities reduce the survival time of patients. Circular RNAs (circRNAs) play an essential role in various tumors, such as regulating tumor cell proliferation, apoptosis, invasion, metastasis, and other progressive phenotypes through different mechanisms. Finding novel circRNAs may significantly contribute to the prognosis of GBM and provide the basis for the targeted therapy of GBM. In this study, we found circPTPRF is a novel circRNA that has never been studied, which was highly expressed in GBM and is closely related to poor patient prognoses. After knockdown or overexpression in glioma cell lines (U87 and LN229) and glioma stem cells (GSCs), we identified that circPTPRF could promote proliferation, invasion, and neurospheres formation abilities of GBM via in vitro and in vivo experiments. Mechanisms, miR-1208 was confirmed as a target of circPTPRF, and miR-1208 can also target the 3'UTR of YY1, and they were proved by luciferase reporter, western blotting (WB), qPCR and RNA immunoprecipitation (RIP) assays. The following rescue experiments demonstrated that circPTPRF was a miR-1208 sponge for upregulating YY1 expression to promote proliferation, invasion and neurosphere formation abilities of GBM in vitro. In conclusion, the circPTPRF/miR-1208/YY1 axis can regulate GBM progression. CircPTPRF may play an essential role in GBM diagnosis and prognostic prediction and be an important molecular target for GBM therapy.

Identification of proteomic markers for prediction of the response to 5-Fluorouracil based neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) prior to surgery is the standard treatment for patients with locally advanced rectal cancer (LARC), while parts of them show poor therapeutic response accompanied by therapy adverse effects. Predictive biomarkers for nCRT response could facilitate the guidance on treatment decisions but are still insufficient until now, which limits the clinical applications of nCRT in LARC patients. METHODS: In our study, 37 formalin-fixed paraffin-embedded tumor biopsies were obtained from patients with LARC before receiving 5-fluorouracil based nCRT. Proteomics analyses were conducted to identify the differentially expressed proteins (DEPs) between total responders (TR) and poor responders (PR). The DEPs were validated via ROC plotter web tool and their predictive performance was evaluated by receiver operating characteristic analysis. Functional enrichment analyses were performed to further explore the potential mechanisms underlying nCRT response. RESULTS: Among 3,998 total proteins, 91 DEPs between TR and PR were screened out. HSPA4, NIPSNAP1, and SPTB all with areas under the curve (AUC) ~ 0.8 in the internal discovery cohort were independently validated by the external mRNA datasets (AUC ~ 0.7), and their protein levels were linearly correlated with the graded responses to nCRT in the internal cohort. The combination of HSPA4 and SPTB could distinctly discriminate the TR and PR groups (AUC = 0.980, p < 0.0001). Moreover, multiple combinations of the three proteins realized increased specificity and/or sensitivity, while achieving favorable predictive value when moderate responders were introduced into the ROC analysis. Pathways including DNA damage repair, cell cycle, and epithelial mesenchymal transition were involved in nCRT response according to the enrichment analysis results. CONCLUSIONS: HSPA4, SPTB and NIPSNAP1 in tumor biopsies and/or their optional combinations might be potential predictive markers for nCRT response in patients with LARC. The DEPs and their related functions have implications for the potential mechanisms of treatment response to nCRT in patients with LARC.

Rhizobium quercicola sp. nov., isolated from the leaf of Quercus variablis in China.

Strain DKSPLA3T, a novel Gram-negative, catalase-positive, oxidase-positive, non-spore-forming, aerobic, non-nitrogen-fixing, non-motile bacterium was isolated from Quercus variablis leaf, in Zunyi, Guizhou, China. Growth occurred at 4-37 °C (optimum 28 °C), pH 4.0-9.0 (optimum pH 7.0) and up to 4.0% (w/v) NaCl (optimum under 2.0%, w/v). Phylogeny based on 16S rRNA gene indicated that strain DKSPLA3T was a novel species in the genus Rhizobium, which was supported by average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values. The predominant fatty acids of strain DKSPLA3T were C16:0, C18:1 ω7c and/or C18:1 ω6c and C18:1 ω7c 11-methyl. The major respiratory quinone was Q-10. Major polar lipids were diphosphatidyl glycerol (DPG), phosphatidyl glycerol (PG), phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PME), phosphatidylcholine (PC), two unidentified phospholipids (PL) and nine unidentified lipids (L). The genomic G + C content was 64.47 mol%. Based on the phenotypic, phylogenetic and genotypic data, DKSPLA3T should be classified as a novel species in the genus Rhizobium, for which the name Rhizobium quercicola sp. nov. (KCTC 82843T = CFCC 16,707T) is proposed.

Detection system of the lobster eye telescope with large field of view.

The lobster eye telescope is promising for large-field x ray imaging in astronomy. The special structure of the lobster eye system makes the focal plane a sphere, resulting in detector defocus when the field is large. In this study, we established a model based on the principle of lobster eye imaging and simulated the imaging at different image distances. The results reveal the relationship between the defocus and position accuracy and angular resolution. To ensure the optical performance of the large field lobster eye telescope, we propose a detection system design method using multiple detectors stitched together to form a spherical-like surface and apply it to the development of the Einstein Probe/wide-field x ray telescope (EP/WXT) submodule. About 70% of the detection area is out of focus within 0.5 mm. The scanning image of the integrated WXT submodule shows good uniformity of the point spread function (PSF) for various incident angles, and the effect of defocus on imaging is acceptable.

Systematic study on expression and prognosis of E2Fs in human colorectal cancer.

BACKGROUND: E2Fs are important components of transcription factors and play key roles in occurrence or advancement of various cancers, but the expression and exact roles of each E2F in colorectal cancer (CRC) are rarely known. METHODS: To address this issue, we investigated the roles and prognostic values of E2Fs expressions in CRC patients by searching ONCOMINE, cBioPortal, GEPIA, Matascape and UALCAN. RESULTS: E2F1, 3-8 were upregulated at the mRNA level and E2F2 was less expressed in CRC tissues than in normal tissues. The eight E2Fs were correlated with tumor stages of CRC. Survival analysis using GEPIA revealed that high expressions of E2F3, 4 were related with short overall survival in all CRC patients. The mutation rate of E2Fs (60%) was high and genetic alteration in E2Fs was linked with longer overall survival in CRC patients. Functional analysis implied that E2Fs and their 50 nearby genes were concentrated in tumor-related pathways. CONCLUSIONS: E2Fs may be candidate biomarkers for CRC diagnosis and E2F3, 4 are potential prognosis biomarkers of CRC. Nevertheless, our findings must be validated in the future to popularize the clinical application of E2Fs in CRC.

Effect of Volatile Anesthetics on Myocardial Infarction After Coronary Artery Surgery: A Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

Inhibition of human sperm function by an antibody against apolipoprotein A1: A protein located in human spermatozoa.

Apolipoproteins A1 (ApoA1), an important protein in initiating sperm capacitation, has been found in the oviduct liquid, whilst whether it expresses in human spermatozoa has not yet been defined. ApoA1 expression was detected by reverse transcription-polymerase chain reaction, Western blot and immunofluorescence in sperm cells. Sperms were incubated with different concentration of ApoA1 antibody to observe the changes of sperm motility and apoptosis including annexin V binding to the cell surface, mitochondrial membrane potential and ultrastructural changes. In addition, cholesterol levels of human spermatozoa and fertilization in vitro were completed to explore the role of ApoA1 in fertilization process. We identify ApoA1 mRNA is presented in spermatozoa, and the ApoA1 protein, the molecular weights of 31 kD, is located at the postacrosomal region and neck of human spermatozoa. ApoA1 antibody affects cholesterol efflux of human spermatozoa and inhibits fertilization in vitro. Moreover, ApoA1 antibody decreases sperm motility and increases sperm apoptosis. This work shows ApoA1 plays an important role in maintaining cholesterol stability and sperm motility, survival rate and fertilization process. Furthermore, ApoA1 implications in the clinical work and other reproductive areas are needed to be studied.

A Bibliometric Analysis of Overall and Top 100 Most-Cited Studies About Robotic Surgery Versus Open Surgery.

BACKGROUND: In the last 30 years, significant progress in the field of surgery has been achieved with the advent of robotic surgery. In this study, we aimed to conduct a bibliometric analysis to identify the distribution and characteristics overall and of the top 100 most-cited studies about robotic surgery versus open surgery. METHODS: A systematic search was conducted on March 26, 2021 using Web of Science Core Collection. Two reviewers independently screened documents, and the top 100 most-cited studies were identified. Excel 2019 and VOSviewer were used to collect the data, and visual information was obtained. RESULTS: A total of 2306 documents were searched from the Web of Science Core Collection, and 1065 journals and 2913 institutes were extracted. A significant growth was observed in the last 15 years. The number of citations from the United States accounted for 33.31% of the total number of citations. There were nine American institutes and one Swedish institute in the top 10 institutes. Four journals in the field of urology or gynecology were present in the top 10 published journals. Few global communications between authors, institutes, and countries authors were observed. CONCLUSION: The lack of close cooperation among scientific research institutions may have affected the industrialization process of surgical robots. Some developing countries, including South America and Africa, should seize the development opportunity of robotic surgery to improve the level of domestic research on robotic surgery.

ITIH4, as an inflammation biomarker, mainly increases in bacterial bloodstream infection.

Bloodstream infection (BSI) is usually accompanied with the changes of varieties of inflammation proteins. In our previous study, we identified that inter-α-trypsin inhibitor heavy chain H4 (ITIH4) was highly expressed in the infection arms than the normal control arm. However, the correlated verification and mechanism remain obscure. Escherichia coli infected mice model and clinical serum samples were used to validate the concentration of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), as well as ITIH4, in ELISA method. Cytokines (IL-6, TNF-α, IL-10 and lipopolysaccharide (LPS)) were used to stimulate the HepG2 cell model to explore which cytokines influence the expression of ITIH4. JAK/STAT inhibitor was treated before IL-6 and LPS stimulation. Westernblot, as well as real-time PCR were performed to detect the expression of ITIH4 in liver tissue from protein and transcription levels. Immunohistochemistry analysis was used to observe the expression of ITIH4 in mice liver tissue. In mice model, IL-6, TNF-α, as well as IL-10 increased in the infection arms than the normal control arm. ITIH4 in serum and liver tissue of mice model increased from 1 h to 128 h, which were remarkably different from that of the normal control arm. Besides, ITIH4 increased in the bacterial infection arm greatly than the fungemia arm, mycoplasma pneumoniae (MP) arm and febrile arm in clinical serum samples. Furthermore, using the HepG2 cell line, we demonstrated that ITIH4 was up-regulated at both protein and mRNA levels upon dose- and time- response treatments with IL-6, as well as LPS. Moreover, IL-6 or LPS mediated induction of ITIH4 expression could be significantly decreased by treatment with an JAK/STAT inhibitor in protein or mRNA level. No changes were observed after TNF-α or IL-10 stimulation. ITIH4 might be a critical inflammatory biomarker which correlated with the development of BSI, especially with bacterial bloodstream infection. It is expected that this study would provide some insights into potential functional mechanisms underlying BSI.

Research and progress on biomarkers of neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) are a demyelinating disorder of the central nervous system based on the involvement of the optic nerve and/or spinal cord. The disease is characterized by high recurrence and disability. NMOSD is mainly diagnosed by AQP4-IgG and MOG-IgG. However, there are still some patients with negative or undetermined double-antibody, and AQP4-IgG and MOG-IgG cannot indicate the clinical disease activity. Therefore, it is urgent to explore interesting biomarkers in serum and cerebrospinal fluid to promote early clinical diagnosis and/or as a target for diagnosis and treatment. This article summarized the research progress in serum and cerebrospinal fluid biomarkers of astrocytes, neurons, myelin sheath, and other damage after the onset of NMOSD. Besides the value of microglial activation-related proteins in the diagnosis and treatment of NMOSD was prospected, so as to promote the research progress of NMOSD.

Fibronectin and colorectal cancer: signaling pathways and clinical implications.

Colorectal cancer (CRC) is the fourth leading cause of cancer deaths worldwide, with poor prognosis mainly related to metastasis. Fibronectin (FN), a vital component of the extracellular matrix (ECM), has been found involved in tumorigenesis and malignant progression in different types of malignancy. Numerous studies have indicated the distinct expression of FN in various cancers and demonstrated the different functions of FN in the proliferation, migration, and invasion of cancers. Meanwhile, FN isoforms have been extensively used for targeted drug delivery and imaging for tumors. Although a growing number of studies on FN in CRC have been reported, integrated reviews on the relationship between FN and CRC are rare. In this review, we will summarize the association between FN and CRC, including the signaling pathways and molecules involved in, as well as potential diagnostic and therapeutic values of FN for patients with CRC.

IFCC interim guidelines on rapid point-of-care antigen testing for SARS-CoV-2 detection in asymptomatic and symptomatic individuals.

With an almost unremittent progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections all around the world, there is a compelling need to introduce rapid, reliable, and high-throughput testing to allow appropriate clinical management and/or timely isolation of infected individuals. Although nucleic acid amplification testing (NAAT) remains the gold standard for detecting and theoretically quantifying SARS-CoV-2 mRNA in various specimen types, antigen assays may be considered a suitable alternative, under specific circumstances. Rapid antigen tests are meant to detect viral antigen proteins in biological specimens (e.g. nasal, nasopharyngeal, saliva), to indicate current SARS-CoV-2 infection. The available assay methodology includes rapid chromatographic immunoassays, used at the point-of-care, which carries some advantages and drawbacks compared to more conventional, instrumentation-based, laboratory immunoassays. Therefore, this document by the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Taskforce on COVID-19 aims to summarize available data on the performance of currently available SARS-CoV-2 antigen rapid detection tests (Ag-RDTs), providing interim guidance on clinical indications and target populations, assay selection, and evaluation, test interpretation and limitations, as well as on pre-analytical considerations. This document is hence mainly aimed to assist laboratory and regulated health professionals in selecting, validating, and implementing regulatory approved Ag-RDTs.

A Compound Heterozygosis of Two Novel Mutations Causes Factor X Deficiency in a Chinese Pedigree.

BACKGROUND: Mutations in the F10-coding gene can cause factor X (FX) deficiency, leading to abnormal coagulation activity and severe tendency for hemorrhage. Therefore, identifying mutations in F10 is important for diagnosing congenital FX deficiency. METHODS: We studied a 63-year-old male patient with FX deficiency and 10 of his family members. Clotting and immunological methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, and FX antigen levels. The platelet count was determined. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulant. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. RESULTS: Genetic analysis of the proband identified two single-base substitutions: c.1085G>A (p.Ser362Asn) and c.1152C>A (p.Tyr384Ter, termination codon, caused by the DNA sequence TAA). His FX activity and antigen levels were 1.7% and 408.53 pg/mL, respectively; aPTT and PT were 52.3 and 48.0 s, respectively. One brother had the same compound heterozygous mutations, and his FX activity and antigen levels were 1.3% and 465.47 pg/mL, respectively; his aPTT and PT were 65.2 and 54.5 s, respectively. His mother, another brother, and one sister were heterozygous for c.1085G>A (p.Ser362Asn), and his daughter and grandson (6 years old) were heterozygous for c.1152C>A (p.Tyr384Ter). CONCLUSION: The heterozygous variants p.Ser362Asn or p.Tyr384Ter indicate mild FX deficiency, but the compound heterozygous mutation of the two causes severe congenital FX deficiency and bleeding. Genetic analysis of these two mutations may help characterize the bleeding tendency and confirm congenital FX deficiency.

Association of Growth Differentiation Factor-15 Polymorphisms and Growth Differentiation Factor-15 Serum Levels with Susceptibility to Multiple Myeloma in a Chinese Population.

BACKGROUND: The aim of our study was to evaluate the relationship between growth differentiation factor-15 (GDF15) rs1058587, rs4808793, and rs1059369 polymorphisms, serum concentrations of GDF15, and International Staging System (ISS) staging or Durie-Salmon staging system (DS) staging in multiple myeloma patients and whether its polymorphism affects the expression of serum GDF15 in Chinese population. METHODS: A total of 120 patients with multiple myeloma and 119 healthy controls were included in the study. The SNaPshot technique was used to detect the GDF15 gene polymorphisms. Serum GDF15 levels were measured using an Enzyme-Linked ImmunoSorbent Assay (ELISA) kit. RESULTS: There was no significant difference in genotype distribution or allele frequency of three loci between multiple myeloma patients and healthy controls. However, the genotype distribution and allele frequencies of rs1059369 in ISS stage I were significantly different from those in ISS stage II (p = 0.008), and the distribution of rs1058587 genotype was different between ISS stage II and ISS stage III (p = 0.014). The overall serum concentration of GDF15 and the same genotype at the same locus (rs1058587: GC, GG; rs4808793: CC, GC; rs1059369: AA, AT, and TT) in patients with multiple myeloma was significantly higher than in the healthy control group (all p < 0.05). CONCLUSIONS: Our results showed the genotype distribution and allele frequencies of rs1059369 and rs1058587 of GDF15 gene have some association with ISS and DS stage. But the polymorphism of GDF15 did not affect the expression of serum GDF15 in patients with multiple myeloma.