Predictive value of dynamic changes in peripheral blood inflammation and blood lipid-related indices for the lung cancer treatment efficacy.

To investigate the dynamics of inflammation and lipid-related indicators in lung cancer patients and their impact on treatment efficacy. A retrospective analysis was conducted on 133 lung cancer patients who seek for primary treatment at Wujin Hospital Affiliated to Jiangsu University from January 2019 to August 2022. The inflammation and blood lipid-related indicators were collected 1 week before treatment and after 2 cycles of treatment. We compared the changes in these indicators among patients with different treatment methods and outcomes. The diagnostic value of the dynamic changes in each index for disease progression was calculated using the ROC curve. The risk factors influencing disease development were identified using multifactorial logistic regression analysis. After 2 cycles of treatment, the white blood cell count (WBC, P<0.001), neutrophil count (NC, P<0.001), neutrophil-to-lymphocyte ratio (NLR, P<0.001) in the disease progression (PD) group were significantly increased, triglyceride (TG, P=0.023), apolipoprotein A1 (APO-A1, P=0.009) was significantly decreased. The results showed that ∆NC had the highest sensitivity (88.24%) in predicting disease progression, and ∆WBC had the best specificity (77.78%). Multivariate regression analysis showed that ΔWBC (P<0.001), ΔTG (P=0.041), and treatment method (P=0.010) were independent risk factors for disease progression (PD). The changes of WBC and TG before and after treatment are promising indicators for predicting the progression of lung cancer and may offer a new direction for lung cancer treatment.

Neutrophil-to-Lymphocyte Ratio and Procalcitonin in Sepsis Patients: Do They Have Any Prognostic Significance?

INTRODUCTION: Biomarkers like white blood cells, C-reactive protein, procalcitonin, and interleukin-1 are used in patients with sepsis for early diagnosis, differentiating various infections, making decisions to start antibiotics and evaluate their response, and to prognosticate morbidity and mortality. Despite the availability of these biomarkers, the prognosis of patients with sepsis in the ICU remains poor. Hence, this study was carried out to test the efficacy of procalcitonin and neutrophil-to-lymphocyte ratio (NLR) to prognosticate mortality and morbidity in terms of incidence of organ dysfunction and length of ICU stay in sepsis patients. METHODS: In this prospective observational study, we measured NLR and procalcitonin at days one, three, and seven of sepsis patients and divided them into four groups: low NLR and high procalcitonin (LNHP), high NLR and high procalcitonin (HNHP), high NLR and low procalcitonin (HNLP), and low NLR and low procalcitonin (LNLP). Mortality at 28 days was noted as the primary outcome. RESULTS: Out of 85 patients included in the study, five were lost to follow-up. Although no statistically significant difference was found in the primary outcome between all four groups, regression analysis showed that rising NLR and procalcitonin values were associated with a significant increase in mortality. CONCLUSION: Serial values of NLR and procalcitonin are more important in predicting severity in comparison to a single value at presentation and can be used as a prognostic marker in sepsis patients.

Phylogenomics of Plant NLR Immune Receptors to Identify Functionally Conserved Sequence Motifs.

In recent years, the increase in genome sequencing across diverse plant species has provided a significant advantage for phylogenomics studies, allowing the analysis of one of the most diverse gene families in plants: nucleotide-binding leucine-rich repeat receptors (NLRs). However, due to the sequence diversity of the NLR gene family, identifying key molecular features and functionally conserved sequence patterns is challenging through multiple sequence alignment. Here, we present a step-by-step protocol for a computational pipeline designed to identify evolutionarily conserved motifs in plant NLR proteins. In this protocol, we use a large-scale NLR dataset, including 1,862 NLR genes annotated from monocot and dicot species, to predict conserved sequence motifs, such as the MADA and EDVID motifs, within the coiled-coil (CC)-NLR subfamily. Our pipeline can be applied to identify molecular signatures that have remained conserved in the gene family over evolutionary time across plant species. Key features • Phylogenomics analysis of plant NLR immune receptor family. • Identification of functionally conserved sequence patterns among plant NLRs.

The prognostic value of the combined neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-platelet ratio (NPR) in sepsis.

Sepsis is a severe disease characterized by high mortality rates. Our aim was to develop an early prognostic indicator of adverse outcomes in sepsis, utilizing easily accessible routine blood tests. A retrospective analysis of sepsis patients from the MIMIC-IV database was conducted. We performed univariate and multivariate regression analyses to identify independent risk factors associated with in-hospital mortality within 28 days. Logistic regression was utilized to combine the neutrophil-to-lymphocyte ratio (NLR) and the neutrophil-to-platelet ratio (NPR) into a composite score, denoted as NLR_NPR. We used ROC curves to compare the prognostic performance of the models and Kaplan-Meier survival curves to assess the 28 day survival rate. Subgroup analysis was performed to evaluate the applicability of NLR_NPR in different subpopulations based on specific characteristics. This study included a total of 1263 sepsis patients, of whom 179 died within 28 days of hospitalization, while 1084 survived beyond 28 days. Multivariate regression analysis identified age, respiratory rate, neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR), hypertension, and sequential organ failure assessment (SOFA) score as independent risk factors for 28 day mortality in septic patients (P < 0.05). Additionally, in the prediction model based on blood cell-related parameters, the combined NLR_NPR score exhibited the highest predictive value for 28 day mortality (AUC = 0.6666), followed by NLR (AUC = 0.6456) and NPR (AUC = 0.6284). Importantly, the performance of the NLR_NPR score was superior to that of the commonly used SOFA score (AUC = 0.5613). Subgroup analysis showed that NLR_NPR remained an independent risk factor for 28 day in-hospital mortality in the subgroups of age, respiratory rate, and SOFA, although not in the hypertension subgroup. The combined use of NLR and NPR from routine blood tests represents a readily available and reliable predictive marker for 28 day mortality in sepsis patients. These results imply that clinicians should prioritize patients with higher NLR_NPR scores for closer monitoring to reduce mortality rates.

PROGNOSTIC VALUES OF NEUTROPHIL/LYMPHOCYTE RATIO IN SEVERE BURN PATIENTS.

The aim of this study was to evaluate the characteristics and prognostic value of the neutrophil/lymphocyte ratio (NLR) in patients with severe burns. A retrospective study was conducted on 245 burn patients over 18 years old without comorbidity or combined injury, burn extent ≥20% TBSA, hospitalized within 24 hours after burn. The collected criteria included patient characteristics, NLR on admission, 3rd and 7th day after burn, and outcome. The results showed that NLR was higher than the normal value at all collected times. In addition, compared to the survivor group, NLR on admission, 3rd and 7th day after burn was significantly higher in the mortality group (p <.01). Multivariate analysis found that the NLR on the 7th day postburn was an independent factor associated with mortality (p <.05), along with the increase in age, burn extent, and presence of inhalation injury (AUC = .85; cut off: 14.13; sensitivity: 75% and specificity: 83.43%). In conclusion, NLR on the 7th day post burn may be used as a predictive factor for mortality amongst severe burn patients.

Le but de cette étude est d'évaluer les valeurs et l'intérêt pronostique du rapport neutrophiles/lymphocytes (RNL) chez le patient gravement brûlé. Il s'agit d'une étude rétrospective conduite auprès de 245 adultes (> 18 ans) brûlés sur >20% SCT, sans inhalation de fumée ni comorbidité, hospitalisés dans les 24h suivant le traumatisme. Nous avons examiné les caractéristiques du patient, les RNL à J3 et J7 ainsi que le devenir. Les RNL étaient systématiquement élevés, significativement plus chez ceux destinés à mourir (p <0,01). En analyse multivariée, la valeur de RNL à J7 est significativement corrélée à la mortalité (p <0,05), comme l'âge, la surface brûlée et l'inhalation. Au seuil de 14,13 on obtient une sensibilité de 75%, une spécificité de 83,43% et une AUC/ROC de 0,85. Le RNL à J7 peut être utilisé comme paramètre prédictif de mortalité chez les patients gravement brûlés.

From inflammatory signaling to neuronal damage: Exploring NLR inflammasomes in ageing neurological disorders.

The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.

Prognostic significance of serum Chemerin and neutrophils levels in patients with oral squamous cell carcinoma.

Objectives: Chemerin, as a novel multifunctional adipokine, is proposed to be involved in high cancer risk and mortality. The present study was aimed to evaluate the prognostic value of serum Chemerin and neutrophils in patients with oral squamous cell carcinoma (OSCC). Materials and methods: 120 patients with OSCC were included in this prospective cohort study. The levels of serum Chemerin were measured by enzyme-linked immunosorbent assay (ELISA). We also explored the possible effects of Chemerin on neutrophils' chemokines in OSCC using a real-time PCR, western blotting. Results: Levels of serum Chemerin, neutrophils and NLR were significantly higher among non-survivors compared to survivors of OSCC (both P < 0.05). Higher serum Chemerin levels were associated with advanced TNM stage, lymph node metastasis, differentiation and tumor recurrence (both P < 0.05). Serum Chemerin levels correlated with neutrophils and NLR levels (r = 0.708, r = 0.578, both P < 0.05). Based on ROC analysis, Chemerin + NLR predicted OSCC patient mortality with 81.54 % sensitivity and 87.27 % specificity, with an AUC of 0.8898. In a Kaplan-Meier analysis, high serum Chemerin levels, high neutrophil levels and high NLR levels were associated with shorter overall and disease-free survival (both P < 0.05). A univariate and multivariate Cox regression analysis showed that serum Chemerin and neutrophils were independent risk factors for OSCC. (both P < 0.05). QRT-PCR and western blotting results showed that Chemerin upregulated the expression of chemokines IL-17 and CXCL-5 in neutrophils (both P < 0.05). Conclusions: Our study suggests that measurement of serum Chemerin and neutrophils might be a useful diagnostic and prognostic biomarker for OSCC patients. Chemerin may promote neutrophils infiltration in OSCC through upregulation of chemokines IL17 and CXCL-5.

Effects of Viral Infections Like COVID-19 on Head and Neck Cancers: The Role of Neutrophil-Lymphocyte Counts and Ratios.

BACKGROUND: Over the last three years, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a global impact. COVID-19 has led to diagnostic and treatment delays in head and neck squamous cell cancers (HNSCCs). Both cancer and COVID-19 trigger systemic inflammatory responses that can result in cytokine storms, creating a favorable tumor microenvironment that supports tumor growth. Various studies have shown a positive association between increasing neutrophil-to-lymphocyte ratio (NLR) and disease severity in COVID-19. Studies have also shown that high NLR is associated with poor survival outcomes in cancer patients. Our aim is to investigate whether an increased NLR is linked to rapid tumor progression in patients with HNSCC who have also been affected by infections like COVID-19 in the pre-operative period. METHODS: This was a retrospective analysis of patients of HNSCC who were scheduled for surgery and had contracted COVID-19 in their pre-operative period between April 2021 and May 2021. The study analyzed pre- and post-COVID NLR in relation to disease progression in HNSCC. Statistical analysis was presented as an interquartile range and numbered with the percentage. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 26.0, Armonk, NY) was utilized for the analysis. RESULTS: We evaluated 200 operable cases of which 38/200 (20%) patients with HNSCC were COVID-19 positive. Out of those COVID-19-positive patients, 27/38 (71%) patients got operated. Around, 11/38 (28.9%) patients were inoperable. And, 14/27 (53.8%) operated patients also had a change in treatment plan. The mean duration from the joint clinic treatment plan to the date of surgery was 25.18 days. Patients who had contracted COVID-19 and had a change in their treatment plan due to disease progression exhibited mean NLR values of 3.84 (pre-COVID) and 11.11 (post-COVID), with respective medians of 3.04 and 10.50. These differences showed a statistically significant p-value of 0.000. In contrast, patients who had no change in treatment plan displayed mean NLR values of 4.51 (pre-COVID) and 9.70 (post-COVID), with respective medians of 3.47 and 3.42, resulting in with a non-significant p-value of 0.082. CONCLUSION: This is a one-of-its-kind study that has evaluated the role of elevated NLR in patients with a COVID-19 virus infection and its relationship with the clinical progression of the disease. The findings suggest that elevated NLR in patients with HNSCC, along with concurrent SARS-CoV2 infection, may contribute to accelerated disease progression with an increase in tumor burden and nodal metastasis.

Evolutionary and immune-activating character analyses of NLR genes in algae suggest the ancient origin of plant intracellular immune receptors.

Nucleotide-binding leucine-rich repeat (NLR) proteins are crucial intracellular immune receptors in plants, responsible for detecting invading pathogens and initiating defense responses. While previous studies on the evolution and function of NLR genes were mainly limited to land plants, the evolutionary trajectory and immune-activating character of NLR genes in algae remain less explored. In this study, genome-wide NLR gene analysis was conducted on 44 chlorophyte species across seven classes and seven charophyte species across five classes. A few but variable number of NLR genes, ranging from one to 20, were identified in five chlorophytes and three charophytes, whereas no NLR gene was identified from the remaining algal genomes. Compared with land plants, algal genomes possess fewer or usually no NLR genes, implying that the expansion of NLR genes in land plants can be attributed to their adaptation to the more complex terrestrial pathogen environments. Through phylogenetic analysis, domain composition analysis, and conserved motifs profiling of the NBS domain, we detected shared and lineage-specific features between NLR genes in algae and land plants, supporting the common origin and continuous evolution of green plant NLR genes. Immune-activation assays revealed that both TNL and RNL proteins from green algae can elicit hypersensitive responses in Nicotiana benthamiana, indicating the molecular basis for immune activation has emerged in the early evolutionary stage of different types of NLR proteins. In summary, the results from this study suggest that NLR proteins may have taken a role as intracellular immune receptors in the common ancestor of green plants.

Bioengineering a plant NLR immune receptor with a robust binding interface toward a conserved fungal pathogen effector.

Bioengineering of plant immune receptors has emerged as a key strategy for generating novel disease resistance traits to counteract the expanding threat of plant pathogens to global food security. However, current approaches are limited by rapid evolution of plant pathogens in the field and may lack durability when deployed. Here, we show that the rice nucleotide-binding, leucine-rich repeat (NLR) immune receptor Pik-1 can be engineered to respond to a conserved family of effectors from the multihost blast fungus pathogen Magnaporthe oryzae. We switched the effector binding and response profile of the Pik NLR from its cognate rice blast effector AVR-Pik to the host-determining factor pathogenicity toward weeping lovegrass 2 (Pwl2) by installing a putative host target, OsHIPP43, in place of the native integrated heavy metal-associated domain (generating Pikm-1OsHIPP43). This chimeric receptor also responded to other PWL alleles from diverse blast isolates. The crystal structure of the Pwl2/OsHIPP43 complex revealed a multifaceted, robust interface that cannot be easily disrupted by mutagenesis, and may therefore provide durable, broad resistance to blast isolates carrying PWL effectors in the field. Our findings highlight how the host targets of pathogen effectors can be used to bioengineer recognition specificities that have more robust properties compared to naturally evolved disease resistance genes.

Role of leukocyte parameters in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with high thrombus burden.

Objective: Leukocyte parameters are associated with cardiovascular diseases. The aim of the present study was to investigate the role of leukocyte parameters in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) with high thrombus burden (HTB). Methods: A total of 102 consecutive STEMI patients with HTB who underwent PPCI within 12 h from the onset of symptoms between June 2020 and September 2021 were enrolled in this study. In addition, 101 age- and sex-matched STEMI patients with low thrombus burden (LTB) who underwent PPCI within 12 h from the onset of symptoms were enrolled as controls. Leukocyte parameters, such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), were calculated at the time of admission. Results: The value of NLR and MLR were significantly higher in the HTB group than in the LTB group (6.24 ± 4.87 vs. 4.65 ± 3.47, p = 0.008; 0.40 ± 0.27 vs. 0.33 ± 0.20, p = 0.038). A cutoff value of >5.38 for NLR had a sensitivity and specificity of 53.9% and 74.3%, respectively, and MLR >0.29 had a sensitivity and specificity of 60.8% and 55.4%, respectively, for determining the STEMI patients with HTB [area under the receiver operating characteristic curve (AUC): 0.603, 95% confidence interval (CI): 0.524-0.681, p = 0.012; AUC: 0.578, 95% CI: 0.499-0.656, p = 0.046]. There was no significant difference of all-cause mortality rate and major adverse cardiac events (MACEs) between the STEMI patients with HTB or with LTB (3.92% in HTB group vs. 2.97% in LTB group, p = 0.712; 10.78% in HTB group vs. 8.91% in LTB group, p = 0.215). Compared with the HTB patients in the low NLR group, C-reactive protein, baseline troponin I, baseline brain natriuretic peptide, and leukocyte parameters, such as white blood cell, neutrophil, lymphocyte, NLR, PLR, and MLR, were also significantly higher in the high NLR group in STEMI patients who underwent PPCI with HTB (18.94 ± 19.06 vs. 35.23 ± 52.83, p = 0.037; 10.99 ± 18.07 vs. 21.37 ± 19.64, p = 0.007; 199.39 ± 323.67 vs. 430.72 ± 683.59, p = 0.028; 11.55 ± 3.56 vs. 9.31 ± 2.54, p = 0.001; 9.77 ± 3.17 vs. 5.79 ± 1.97, p = 0.000; 1.16 ± 0.44 vs. 2.69 ± 1.23, p = 0.000; 9.37 ± 4.60 vs 1.31 ± 2.58, p = 0.000; 200.88 ± 89.90 vs. 97.47 ± 50.99, p = 0.000; 0.52 ± 0.29 vs. 0.26 ± 0.14, p = 0.000, respectively). MACEs and heart failure in the high NLR group were significantly higher than that in the low NLR group of STEMI patients who underwent PPCI with HTB (20.45% vs. 4.25%, p = 0.041; 10.91% vs. 2.13%, p = 0.038). Conclusion: The value of NLR and MLR were higher in STEMI patients who underwent PPCI with HTB. In STEMI patients who underwent PPCI with HTB, a raised NLR could effectively predict the occurrence of MACEs and heart failure.

A Coiled-Coil Nucleotide-Binding Domain Leucine-Rich Repeat Receptor Gene MeRPPL1 Plays a Role in the Replication of a Geminivirus in Cassava.

Disease resistance gene (R gene)-encoded nucleotide-binding leucine-rich repeat proteins (NLRs) are critical players in plant host defence mechanisms because of their role as receptors that recognise pathogen effectors and trigger plant effector-triggered immunity (ETI). This study aimed to determine the putative role of a cassava coiled-coil (CC)-NLR (CNL) gene MeRPPL1 (Manes.12G091600) (single allele) located on chromosome 12 in the tolerance or susceptibility to South African cassava mosaic virus (SACMV), one of the causal agents of cassava mosaic disease (CMD). A transient protoplast system was used to knock down the expression of MeRPPL1 by clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9). The MeRPPL1-targeting CRISPR vectors and/or SACMV DNA A and DNA B infectious clones were used to transfect protoplasts isolated from leaf mesophyll cells from the SACMV-tolerant cassava (Manihot esculenta) cultivar TME3. The CRISPR/Cas9 silencing vector significantly reduced MeRPPL1 expression in protoplasts whether with or without SACMV co-infection. Notably, SACMV DNA A replication was higher in protoplasts with lower MeRPPL1 expression levels than in non-silenced protoplasts. Mutagenesis studies revealed that protoplast co-transfection with CRISPR-MeRPPL1 silencing vector + SACMV and transfection with only SACMV induced nucleotide substitution mutations that led to altered amino acids in the highly conserved MHD motif of the MeRPPL1-translated polypeptide. This may abolish or alter the regulatory role of the MHD motif in controlling R protein activity and could contribute to the increase in SACMV-DNA A accumulation observed in MeRPPL1-silenced protoplasts. The results herein demonstrate for the first time a role for a CNL gene in tolerance to a geminivirus in TME3.

NLRP3 promotes allergic responses to birch pollen extract in a model of intranasal sensitization.

Introduction & Objective: Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully elucidated. Recent scientific advances have highlighted the importance of the allergen context. In this regard, microbial patterns (PAMPs) present on BP have attracted increasing interest. As these PAMPs are recognized by specialized pattern recognition receptors (PRRs), this study aims at investigating the roles of intracellular PRRs and the inflammasome regulator NLRP3. Methods: We established a physiologically relevant intranasal and adjuvant-free sensitization procedure to study BP-induced systemic and local lung inflammation. Results: Strikingly, BP-sensitized Nlrp3-deficient mice showed significantly lower IgE levels, Th2-associated cytokines, cell infiltration into the lung, mucin production and epithelial thickening than their wild-type counterparts, which appears to be independent of inflammasome formation. Intriguingly, bone-marrow chimera revealed that expression of NLRP3 in the hematopoietic system is required to trigger an allergic response. Conclusion: Overall, this study identifies NLRP3 as an important driver of BP-induced allergic immune responses.

Neutrophil-to-lymphocyte ratio is elevated in acute hantavirus infection and correlates with markers of disease severity.

Pathogenic Eurasian hantaviruses cause hemorrhagic fever with renal syndrome (HFRS), which is characterized by acute kidney injury. The clinical course shows a broad range of severity and is influenced by direct and immune-mediated effects. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and predicts severity and outcome in various diseases. Therefore, we examined the role of NLR in HFRS caused by hantavirus Puumala (PUUV) and its association with disease severity and kidney injury. We detected elevated NLR levels on admission (NLRadm: median 3.82, range 1.75-7.59), which increased during acute HFRS. Maximum NLR levels (NLRmax: median 4.19, range 1.75-13.16) were 2.38-fold higher compared to the reference NLR level of 1.76 in the general population. NLR levels on admission correlate with markers of severity (length of hospital stay, serum creatinine) but not with other markers of severity (leukocytes, platelets, C-reactive protein, lactate dehydrogenase, serum albumin, proteinuria). Interestingly, levels of nephrin, which is a specific marker of podocyte damage in kidney injury, are highest on admission and correlate with NLRmax, but not with NLRadm. Together, we observed a correlation between systemic inflammation and the severity of HFRS, but our results also revealed that podocyte damage precedes these inflammatory processes.

Copy number variation and population-specific immune genes in the model vertebrate zebrafish.

Copy number variation in large gene families is well characterized for plant resistance genes, but similar studies are rare in animals. The zebrafish (Danio rerio) has hundreds of NLR immune genes, making this species ideal for studying this phenomenon. By sequencing 93 zebrafish from multiple wild and laboratory populations, we identified a total of 1513 NLRs, many more than the previously known 400. Approximately half of those are present in all wild populations, but only 4% were found in 80% or more of the individual fish. Wild fish have up to two times as many NLRs per individual and up to four times as many NLRs per population than laboratory strains. In contrast to the massive variability of gene copies, nucleotide diversity in zebrafish NLR genes is very low: around half of the copies are monomorphic and the remaining ones have very few polymorphisms, likely a signature of purifying selection.

Humans and other animals have immune systems that protect them from bacteria, viruses and other potentially harmful microbes. Members of a family of genes known as the NLR family play various roles in helping to recognize and destroy these microbes. Different species have varying numbers of NLR genes, for example, humans have 22 NLRs, but fish can have hundreds. 400 have been found in the small tropical zebrafish, also known as zebra danios. Zebrafish are commonly used as model animals in research studies because they reproduce quickly and are easy to keep in fish tanks. Much of what we know about fish biology comes from studying strains of those laboratory zebrafish, including the 400 NLRs found in a specific laboratory strain. Many NLRs in zebrafish are extremely similar, suggesting that they have only evolved fairly recently through gene duplication. It remains unclear why laboratory zebrafish have so many almost identical NLRs, or if wild zebrafish also have lots of these genes. To find out more, Schäfer et al. sequenced the DNA of NLRs from almost 100 zebrafish from multiple wild and laboratory populations. The approach identified over 1,500 different NLR genes, most of which, were previously unknown. Computational modelling suggested that each wild population of zebrafish may harbour up to around 2,000 NLR genes, but laboratory strains had much fewer NLRs. The numbers of NLR genes in individual zebrafish varied greatly ­ only 4% of the genes were present in 80% or more of the fish. Many genes were only found in specific populations or single individuals. Together, these findings suggest that the NLR family has expanded in zebrafish as part of an ongoing evolutionary process that benefits the immune system of the fish. Similar trends have also been observed in the NLR genes of plants, indicating there may be an evolutionary strategy across all living things to continuously diversify large families of genes. Additionally, this work highlights the lack of diversity in the genes of laboratory animals compared with those of their wild relatives, which may impact how results from laboratory studies are used to inform conservation efforts or are interpreted in the context of human health.

The predictive value of serum inflammatory markers for the severity of cervical lesions.

OBJECTIVE: Exploring the predictive value of NLR, PLR, MLR, and SII for the severity of cervical cancer screening abnormalities in patients. METHODS: A retrospective analysis was conducted on the data of 324 patients suspected of cervical lesions due to abnormal TCT and/or HPV in our hospital from January 2023 to December 2023, who underwent colposcopy. The pathological results of colposcopic biopsy confirmed that there were 140 cases of chronic cervicitis, which classified as the group without cervical lesions. The cervical lesion group included 184 cases, including 91 cases of LSIL, 71 cases of HSIL, and 22 cases of cervical cancer. Compared the differences in preoperative peripheral blood NLR, PLR, MLR, and SII among different groups of patients, and evaluated their predictive value for the severity of cervical lesions using Receiver Operating Characteristic (ROC) curves. RESULTS: The levels of NLR, PLR, and SII in the group without cervical lesions were lower than those in the group with cervical lesions (p < 0.05), and there was no statistically significant difference in MLR (p > 0.05). The comparison of NLR among LSIL, HSIL, and cervical cancer groups showed statistically significant differences (p < 0.05), while PLR, MLR, and SII showed no statistically significant differences (p > 0.05). The AUC of peripheral blood NLR, PLR, and SII for predicting cervical lesions were 0.569, 0.582, and 0.572, respectively. The optimal cutoff values were 2.3,176.48, and 603.56. The sensitivity and specificity were 38.6% and 73.6%, 28.8% and 85.7%, 37.5% and 76.4%, respectively. At the same time, the joint testing of the three had the highest efficiency, with sensitivity of 69% and specificity of 45%. CONCLUSION: Although the peripheral blood NLR, PLR, and SII of the cervical lesions patients were higher than those without cervical lesions in cervical cancer screening abnormal patients, the predictive ROC curve discrimination was low. Therefore, it is not recommended to use preoperative peripheral blood inflammatory markers as markers for cervical cancer screening abnormal patient diversion.

The predictive value of hematological inflammatory markers for severe oral mucositis in patients with nasopharyngeal carcinoma during intensity-modulated radiation therapy: A retrospective cohort study.

BACKGROUND: This study aims to investigate the predictive value of the circulating blood cell count, including neutro-philto-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and thesystemic inflammation index (SII) for the development of severe oral mucositis (SOM) induced by radiation in patients undergoing radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 142 NPC patients were screened, and based on mucositis toxicity grade, they were categorized into two groups: SOM and nonSOM. Peripheral blood cell counts were conducted prior to Intensity-Modulated Radiation Therapy (IMRT). Associations between blood cell count, NLR, PLR, SII, and SOM occurrence were examined. RESULTS: Revealed elevated NLR and SII levels, along with reduced lymphocyte (LYM), eosinophil (EOS), and basophil (BAS) in patients with SOM. LYM, EOS, BAS, NLR, and SII were effective predictors of the severity of radiation-induced oral mucositis (RIOM) in NPC patients. CONCLUSIONS: The occurrence of SOM was strongly linked to the hematological status at the start of Radiation Therapy (RT). Integrating BAS count and NLR into comprehensive risk prediction models could prove valuable for predicting SOM in NPC patients.

Influence of Biomarkers on Mortality among Patients with Hepatic Metastasis of Colorectal Cancer Treated with FOLFOX/CAPOX and FOLFIRI/CAPIRI, Including Anti-EGFR and Anti-VEGF Therapies.

Background and objectives: Colorectal cancer is a major global health concern, with a significant increase in morbidity and mortality rates associated with metastatic stages. This study investigates the prognostic significance of various clinical and laboratory parameters in patients with metastatic CRC. Materials and Methods: A retrospective cohort of 188 CRC patients with hepatic metastasis from the OncoHelp Association in Timisoara was analyzed from January 2016 to March 2023. Data on demographics, clinical characteristics, and biomarkers, such as lymphocyte counts, as well as various inflammation indices, were examined. Statistical analyses included univariate and multivariate logistic regression, Kaplan-Meier survival analysis, and ROC curve assessments. Results: Our findings indicate significant associations between survival outcomes and several biomarkers. Higher BMI and lymphocyte counts were linked with better survival rates, while higher values of Neutrophil-Hemoglobin-Lymphocyte (NHL) score, Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), and Systemic Immune-Inflammation Index (SII) were predictors of poorer outcomes. Notably, the presence of hepatic metastasis at diagnosis was a critical factor, significantly reducing overall survival. Conclusions: The study has expanded the current understanding of prognostic factors in CRC, advocating for a multi-dimensional approach to prognostic evaluations. This approach should consider not only the traditional metrics such as tumor stage and histological grading but also incorporate a broader spectrum of biomarkers. Future studies should aim to validate these findings and explore the integration of these biomarkers into routine clinical practice, enhancing the precision of prognostic assessments and ultimately guiding more personalized treatment strategies for CRC patients.

The Diagnostic Accuracy of Procalcitonin and Its Combination with Other Biomarkers for Candidemia in Critically Ill Patients.

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14-0.69) vs. 1.73 (0.5-6.9) ng/mL, p < 0.001, 6.3 (2.4-11.8) vs. 19 (10.7-24.8) mg/dl, p < 0.001 and 6 (3.7-8.6) vs. 9.8 (5.3-16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04-0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia.

Development and evaluation of real-time quantitative PCR assays for detection of Phellinus noxius causing brown root rot disease.

Brown root rot disease (BRRD) is a highly destructive tree disease. Early diagnosis of BRRD has been challenging because the first symptoms and signs are often observed after extensive tissue colonization. Existing molecular detection methods, all based on the internal transcribed spacer (ITS) region, were developed without testing against global Phellinus noxius isolates, other wood decay fungi, or host plant tissues. This study developed SYBR Green real-time quantitative PCR (qPCR) assays for P. noxius. The primer pair Pn_ITS_F/Pn_ITS_R targets the ITS, and the primer pair Pn_NLR_F/Pn_NLR_R targets a P. noxius-unique group of homologous genes identified through a comparative genomics analysis. The homologous genes belong to the nucleotide-binding-oligomerization-domain-like receptor (NLR) superfamily. The new primer pairs and a previous primer pair G1F/G1R were optimized for qPCR conditions and tested for specificity using 61 global P. noxius isolates, five other Phellinus species, and 22 non-Phellinus wood decay fungal species. While all three primer pairs could detect as little as 100 fg (about 2.99 copies) of P. noxius genomic DNA, G1F/G1R had the highest specificity and Pn_NLR_F/Pn_NLR_R had the highest efficiency. To avoid false positives, the cutoff Cq values were determined as 34 for G1F/G1R, 29 for Pn_ITS_F/Pn_ITS_R, and 32 for Pn_NLR_F/Pn_NLR_R. We further validated these qPCR assays using Ficus benjamina seedlings artificially inoculated with P. noxius, six tree species naturally infected by P. noxius, rhizosphere soil, and bulk soil. The newly developed qPCR assays provide sensitive detection and quantification of P. noxius, which is useful for long-term monitoring of BRRD status.