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The problem of identifying the sensitivity of living organisms to ionizing irradiation remains relevant, considering the spread of anthropogenic environmental pollution. The study on the effect of single X-ray irradiation (1,5 Gy) on peripheral blood of bank voles (Myodes glareolus (Schreber, 1780)) captured within territories with background radiation level was conducted. Hematological indicators, characterizing the overall condition of performance of the body, were determined dynamically on the first and seventh days after exposure to detect both early changes and the rate of recovery processes. The patterns and features of the main components of leukocyte formula found in peripheral blood of irradiated animals are being discussed. Differences between irradiated and control mouse-like rodents are shown, using parameters of erythrocytes and leukocytes. The analysis of changes in the peripheral blood of irradiated bank voles indicates the high reserve capacity of the body, according to its ability to restore homeostasis.

Le Xu, Minkang Shi Department of Pediatrics, Liyang People’s Hospital, Liyang, JiangSu, 213300, People’s Republic of ChinaCorrespondence: Minkang Shi, Department of Pediatrics, Liyang People’s Hospital, No. 70 Jianshe West Road, Liyang, JiangSu, 213300, People’s Republic of China, Email smk198403231411@163.comPurpose: Asthma substantially affects the quality of life and health of children. Lipocalin 2 (LCN2) is an immune-related protein, which is predicted to be highly expressed in asthma. Here, we investigated the role of LCN2 in ovalbumin (OVA)-induced asthma mouse model.Methods: We knocked down LCN2 in an asthma mouse model and performed histopathological analysis using hematoxylin and eosin (H&E) staining assay. Differentiated cells were assessed using Diff-Quick staining assay. We investigated the regulatory T (Treg) cell/ T helper 17 (Th17) cell balance using flow cytometry and enzyme-linked immunosorbent assay (ELISA). Inflammatory factors were measured using quantitative real-time reverse transcription PCR (qRT-PCR). The involved pathways were assessed using Western blotting.Results: LCN2 was upregulated in patients with asthma. OVA promoted pathological deterioration in the lungs, increased IgE levels in the plasma, and elevated the number of differentiated inflammatory cells, whereas LCN2 knockdown abrogated the OVA-induced effects. Additionally, the Treg/Th17 imbalance and increased inflammatory cytokine levels were improved by LCN2 knockdown in OVA-treated mice. Moreover, LCN2 knockdown reversed the activation of the janus kinase (JNK) pathway.Conclusion: LCN2 knockdown improved the Treg/Th17 balance, alleviated inflammation, and inactivated the JNK pathway in OVA-induced asthma mouse model, suggesting that LCN2 may be a novel therapeutic target for asthma in children.Keywords: innate immunity, T lymphocyte differentiation, peripheral blood, JNK pathway, inflammation

Background. Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC. Aims. To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease. Methods. Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results. Results. There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017). Conclusion. CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease.

Abstract Background Our understanding of epigenetic modifications in the inner ear is very limited. Although epigenetic regulation of genes related to individual organ- and system-limited pathologies are generally expected to be tissue-specific, DNA methylation patterns in peripheral blood (PB) are found to be associated with the presence of several diseases with no typical hematological involvement. Here, we aimed to investigate whether there is a correlation between hearing-related genes’ promoter region methylation in the PB samples with the presence of non-syndromic sensorineural hearing loss (NSSHL) with an aim of future utilization of DNA methylation as biomarkers in hearing loss. The study included 26 patients with NSSHL and a control group of 20 healthy individuals. CpG islands in the promoter regions of the GJB-2, GJB-6, and SLC24A genes were analyzed using bisulfite sequencing, and methylation percentages were analyzed. Results Methylation levels at the 1st region of GJB-6 and the 1st and the 4th regions of SLC26A4 were found to differ significantly (p = 0.039, p = 0.042, and p = 0.029, respectively) between the patients and the control group. There was no statistically significant difference in methylation percentages of GJB-2 promoters. We also found that parents’ consanguinity determines the methylation levels in patients’ families. Conclusions According to our knowledge, this is the first study that investigates epigenetic changes in the PB of patients with NSSHL. Despite the small sample size, our findings indicate that DNA methylation patterns in the PB could be of use for understanding epigenetic changes in the inner ear and the clinical management of NSSHL.

Objective To explore the role of miR-34a methylation in the development of gastric cancer,and explore the correlation of miR-34a methylation with gastric cancer, pathological features and Helicobacter pylori(HP)infection. Methods The methylation level of miR-34a gene CpG island of thirty-one gastric cancer patients and tweenty-four healthy people were detected by matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry(MALDI-TOF MS)technique. Results The overall average methylation level of miR-34a was higher in gastric cancer than that in the control, the average methylation of miR-34a CpG_5,CpG_12.13 was significantly higher in the gastric cancer group than they were in the control group(51.7%±5.9% vs. 37.8%±7.8%,84.61%±8.2% vs. 68.1%±12.1%,P＜0.01).The methylation level of miR-34a CpG_5 in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group (53.55%±4.86% vs. 47.22%±6.07%,P＜0.01),and the methylation of CpG_5 in TNM stage (stage Ⅱ + stage Ⅲ) was higher than that in stage Ⅰ(53.21%±4.8% vs. 46.57%±6.9%, P＜0.05). Conclusions The miR-34a methylation is potentially associated with the occurrence and development of gastric cancer.

Introduction and hypothesis: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for allogeneic hematopoietic stem cell transplantation in the absence of a compatible donor. The UCB transplantation has a lower incidence of chronic graft versus host disease (GvHD), but is associated with slower engraftment and slower immune reconstitution, compared to other sources. Dendritic cells (DCs) and Natural Killer cells (NKs) play a central role in the development of GvHD and the graft versus leukemia (GvL) effect, as well as in the control of infectious complications. Method: We quantified by multiparametric flow cytometry monocytes, lymphocytes, NK cells, and DCs, including their subsets, in UCB samples from 54 healthy newborns and peripheral blood (PB) from 25 healthy adult volunteers. Results: In the UCB samples, there were higher counts of NK cells 56bright16− (median 0.024 × 109/L), compared to the PB samples (0.012 × 109/L, p

In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.

Background and objective. The prevalence of mild neurocognitive Disorder (MND) has increased after using antiretroviral therapy (ARV), which is around 51.5%. Inflammation plays an essential role in the neurodegenerative state of HIV patients. Peripheral blood images can assess increased macrophage activation by evaluating the number of leukocytes, neutrophils, total lymphocytes, hemoglobin, platelets, platelets, and neutrophil-lymphocyte ratio (NLR) to determine the condition of systemic inflammation in HIV patients with cognitive impairment. This study to know differences in the appearance of peripheral blood in HIV patients with and without cognitive impairment. Method. Observational analytic study with a cross-sectional design on 44 HIV patients who were outpatients at the polyclinic Voluntary Counseling and Testing (VCT) at Prof Dr. IGNG Ngoerah Denpasar Hospital. Subjects were divided into 2 groups based on cognitive status assessed using the MoCA-INA questionnaire. The peripheral blood images considered were the average levels of leukocytes, neutrophils, lymphocytes, hemoglobin, hematocrit, platelets, and the ratio of neutrophils to lymphocytes. Results. 31-40 years old, male, with >9 years of education, has a CD4 count >200, and has received ARV therapy >1 year. The Shapiro-Wilk normality test performed on both groups showed that the data were normally distributed with p>0.05. Bivariate analysis using an independent t-test with a 95% confidence level (α=0.05) found significant differences in mean leukocyte, neutrophil, lymphocyte, and neutrophil-lymphocyte ratios (p

Tomislav M Jelic,1 Oscar C Estalilla,1 Jeffrey A Vos,2 Gary Harvey,1 Caitlin J Stricker,1 Ayodele O Adelanwa,2 Ahmed A Khalid,3 Milton J Plata1 1Department of Pathology and Laboratory Medicine, Charleston Area Medical Center, Charleston, WV, USA; 2Department of Pathology, Anatomy and Laboratory Medicine, West Virginia University School of Medicine, Morgantown, WV, USA; 3Cancer Center, Charleston Area Medical Center, Charleston, WV, USACorrespondence: Tomislav M Jelic, Charleston Area Medical Center, Department of Pathology and Laboratory Medicine, 3200 MacCorkle Avenue, Charleston, WV, 25304, USA, Tel +1 304 546 6714, Email tomilsav.jelic@suddenlink.netBackground and Aims: Significance of absolute number of CD34+ cells in the peripheral blood of patients with less than 1% myeloblasts by manual differential count is unknown and our aim is to study its relevance in clinical practice.Methods: We studied 138 peripheral bloods flow cytometric analyses in patients with less than 1% myeloblasts by manual differential, when CD34+ events were present in the gate that encompassed lymphocytes, monocytes, stem cells, and blasts.Results: The average absolute number of CD34+cells in the peripheral blood was 11 CD34+cells/μL ranging from less than 1 cell/μL to 147 cells/μL. The average absolute number of CD34+ cells in patients with an abnormal expansive process involving bone marrow (metastases, myelodysplasia, granulomas, marrow infections) or if bone marrow biopsy not performed, presumed expansive marrow process was 25 cells/μL, and in patients without an expansive marrow process (or presumed negative) was 4 cells/μL (P< 0.00007). Cutoff 12 CD34+ cells/μL had 93% positive predictive value for bone marrow involvement by an expansive process and 78% negative predictive value.Conclusion: Flow cytometric testing of the peripheral blood is extremely sensitive method for enumerating CD34+ cells and can detect fewer than one CD34+ cell/μL. The absolute number of CD34+ cells in the peripheral blood is a useful parameter in determining marrow involvement by an expansive process and may provide guidance with respect to the necessity for bone marrow biopsy.Keywords: flow cytometry, CD34 positive cells, peripheral blood, myeloblasts, bone marrow biopsy

The paper examines the features of oxygen-dependent metabolism of peripheral blood phagocytes and the nature of its exposure to peptidoglycan and teichoic acid of Staphylococcus aureus. The study included 86 children with purulent and inflammatory processes of staphylococcal etiology aged from 7 months to 12 years and 14 apparently healthy children. The results of the study showed that in most children at the onset of the disease, an increase in the intensity of the oxygen-dependent metabolism of neutrophil granulocytes and monocytes was observed, which was manifested by elevated indicators of the spontaneous HCT test of these cells compared to healthy children. During the period of clinical recovery in children with an acute course of the disease, a significant decrease in spontaneous HST-test indicators was observed. In addition to the spontaneous HCT test, we also studied the indicators of the oxygen-dependent metabolism of neutrophil granulocytes and monocytes after incubation of these cells with cell wall antigens of Staphylococcus aureus – peptidoglycans and teichoic acids. The results of the study showed that after incubation, no significant difference was found between them and the indicators of the spontaneous HCT test. In the period of convalescence in children with acute bronchopneumonia, acute purulent otitis media, acute tonsillitis, a decrease in indicators of oxygen-dependent metabolism was observed after incubation of monocytes with teichoic acids compared to spontaneous indicators. Thus, the effect of cell wall antigens of Staphylococcus aureus on the oxygen-dependent metabolism of neutrophil granulocytes and monocytes of peripheral blood was different. At the beginning of the development of the pathological process, reliable inhibition of the oxygen-dependent metabolism of phagocytes by antigens of the cell wall of Staphylococcus aureus was observed in all clinical groups. In the acute course at the beginning of the disease, the suppression of HST-test indicators was somewhat greater than in the exacerbation of the chronic process. During the recovery of patients with an acute purulent-inflammatory process, reliable inhibition of the oxygen-dependent metabolism of neutrophil granulocytes and monocytes by cell wall antigens of Staphylococcus aureus was not observed, and in children with an exacerbation of the chronic pathological process, the inhibition of the indicators of the HCT test of neutrophil granulocytes and monocytes remained reliably higher and almost did not change compared to the onset of the disease.

Background and objective Immune checkpoint inhibitors (ICIs) therapy lacks viable biomarkers for response and prognosis prediction. This study aimed to investigate the correlation of peripheral blood laboratory test results combined with lymphocyte subset ratios to the response and prognosis of immunotherapy in advanced lung cancer. Methods Advanced lung cancer patients admitted to West China Hospital, Sichuan University from May 2021 to July 2023 were prospectively enrolled in this study. Clinical data and peripheral blood were collected before and after treatment and lymphocyte subset ratios were analyzed by flow cytometry. Logistic regression was used to identify factors correlated to ICIs treatment efficacy. Cox modeling was applied to explore the prognostic factors. Results Logistic regression showed that the baseline level of transcription factor T cell factor 1 (TCF1)+CD8+ T cell ratio and peripheral white blood cell (WBC) count, lymphocyte percentage, cytokeratin 19 fragment (CYFRA21-1) after 1 cycle of ICIs treatment were the potential predictors for ICIs response (P

Abstract Background Essential thrombocythemia (ET) is one of the most common types of Ph-negative myeloproliferative neoplasms, an infrequent group of blood cancers that arise from a CD34 + hematopoietic stem cell (HSC) in the bone marrow (BM) primarily due to driver mutations in JAK2, CALR or MPL. These aberrations result in an overproduction of mature myeloid cells in peripheral blood (PB). To date, no targeted therapies have been approved for ET patients, so the study of the molecular mechanisms behind the disease and the identification of new therapeutic targets may be of interest. For this reason, in this study, we have compared the transcriptomic profile of undifferentiated CD34 + cells and mature myeloid cells from ET patients (CALR and JAK2-mutated) and healthy donors deposited in publicly available databases. The study of the similarities and differences between these samples might help to better understand the molecular mechanisms behind the disease according to the degree of maturation of the malignant clone and the type of mutation and ultimately help identify new therapeutic targets for these patients. Results The results show that most of the altered hallmarks in neutrophils were also found in CD34 + cells. However, only a few genes showed a similar aberrant expression pattern in both types of cells. We have identified a signature of six genes common to patients with CALR and JAK2 mutations (BPI, CRISP3, LTF, MMP8, and PTGS1 upregulated, and PBXIP1 downregulated), a different signature of seven genes for patients with CALR mutations (BMP6, CEACAM8, ITK, LCN2, and PRG2 upregulated, and MAN1A1 and MME downregulated) and a signature of 13 genes for patients with JAK2 mutations (ARG1, CAST, CD177, CLEC5A, DAPP1, EPS15, IL18RAP, OLFM4, OLR1, RIOK3, SELP, and THBS1 upregulated, and IGHM downregulated). Conclusions Our results highlight transcriptomic similarities and differences in ET patients according to the degree of maturation of the malignant clone and the type of mutation. The genes and processes altered in both CD34 + cells and mature neutrophils may reveal altered sustained processes that could be studied as future therapeutic targets for ET patients.

Abstract Background Glioblastoma (GBM) is the most common malignant brain tumor and has “immunologically cold” features. Changing GBM to an “immunologically hot” tumor requires a strong trigger that induces initial immune responses in GBM. Allogeneic natural killer cells (NKCs) have gained considerable attention as promising immunotherapeutic tools against cancer, where gene-edited NKCs would result in effective anti-cancer treatment. The present study focused on the immune checkpoint molecule cytokine-inducible SH2-containing protein (CISH, or CIS) as a critical negative regulator in NKCs. Methods The GBM tumor environment featured with immunological aspect was analyzed with Cancer immunogram and GlioVis. We generated human primary CIS-deleted NKCs (NK dCIS) using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) with single guide RNA targeting genome sites on CIS coding exons. The genome-edited NKCs underwent microarray with differential expression analysis and gene set enrichment analysis (GSEA). The anti-GBM activity of the genome-edited NKCs was evaluated by apoptosis induction effects against allogeneic GBM cells and spheroids. We further detected in vivo antitumor effects using xenograft brain tumor mice. Results We successfully induced human CIS-deleted NKCs (NK dCIS) by combining our specific human NKC expansion method available for clinical application and genome editing technology. CIS gene-specific guide RNA/Cas9 protein complex suppressed CIS expression in the expanded NKCs with high expansion efficacy. Comprehensive gene expression analysis demonstrated increased expression of 265 genes and decreased expression of 86 genes in the NK dCIS. Gene set enrichment analysis revealed that the enriched genes were involved in NKC effector functions. Functional analysis revealed that the NK dCIS had increased interferon (IFN)ɤ and tumor necrosis factor (TNF) production. CIS deletion enhanced NKC-mediated apoptosis induction against allogeneic GBM cells and spheroids. Intracranial administration of the allogeneic NKCs prolonged the overall survival of xenograft brain tumor mice. Furthermore, the NK dCIS extended the overall survival of the mice. Conclusion The findings demonstrated the successful induction of human primary NK dCIS with CRISPR/Cas9 with efficient expansion. CIS deletion enhanced the NKC-mediated anti-tumor effects in allogeneic GBM and could be a promising immunotherapeutic alternative for patients with GBM.

Abstract Background Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease that leads to irreversible damage to the brain and spinal cord. The goal of so-called "immune reconstitution therapies" (IRTs) is to achieve long-term disease remission by eliminating a pathogenic immune repertoire through intense short-term immune cell depletion. B cells are major targets for effective immunotherapy in MS. Objectives The aim of this study was to analyze the gene expression pattern of B cells before and during IRT (i.e., before B-cell depletion and after B-cell repopulation) to better understand the therapeutic effects and to identify biomarker candidates of the clinical response to therapy. Methods B cells were obtained from blood samples of patients with relapsing–remitting MS (n = 50), patients with primary progressive MS (n = 13) as well as healthy controls (n = 28). The patients with relapsing MS received either monthly infusions of natalizumab (n = 29) or a pulsed IRT with alemtuzumab (n = 15) or cladribine (n = 6). B-cell subpopulation frequencies were determined by flow cytometry, and transcriptome profiling was performed using Clariom D arrays. Differentially expressed genes (DEGs) between the patient groups and controls were examined with regard to their functions and interactions. We also tested for differences in gene expression between patients with and without relapse following alemtuzumab administration. Results Patients treated with alemtuzumab or cladribine showed on average a > 20% lower proportion of memory B cells as compared to before IRT. This was paralleled by profound transcriptome shifts, with > 6000 significant DEGs after adjustment for multiple comparisons. The top DEGs were found to regulate apoptosis, cell adhesion and RNA processing, and the most highly connected nodes in the network of encoded proteins were ESR2, PHB and RC3H1. Higher mRNA levels of BCL2, IL13RA1 and SLC38A11 were seen in patients with relapse despite IRT, though these differences did not pass the false discovery rate correction. Conclusions We show that B cells circulating in the blood of patients with MS undergoing IRT present a distinct gene expression signature, and we delineated the associated biological processes and gene interactions. Moreover, we identified genes whose expression may be an indicator of relapse risk, but further studies are needed to verify their potential value as biomarkers.

Objective To investigate the effect of root canal therapy (RCT) on inflammatory cytokines level in peripheral blood, anxiety, and depression in patients with pulpitis. Methods A total of 155 patients with pulpitis admitted to the Stomatology Hospital of the Fourth Military Medical University from June 2021 to June 2022 were treated with root canal therapy. Another 155 persons who received health examinations during the same period were selected as the control group. The Generalized Anxiety Disorder-7 (GAD-7) scores and the Patient Health Questionnaire-9 (PHQ-9) scores of the two groups were compared. The GAD-7, PHQ-9 and pain scores of the test group before treatment and 3 and 6 weeks after treatment were compared. Pain was assessed with a visual analog scale (VAS). Inflammatory cytokine [interleukin-8 (IL-8), interleukin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), c-reactive protein (CRP)] levels in the test group before treatment and 3 and 6 weeks after treatment were compared. Results The GAD-7 and PHQ-9 scores in the test group were higher than those in the control group before treatment (P0.05). The pain scores of the experimental group at 3 and 6 weeks after treatment were lower than those before treatment (P0.05). Conclusion The peripheral blood of patients with pulpitis has a high level of inflammatory cytokines, and the patients suffer from obvious anxiety and depression. Root canal therapy can relieve their anxiety and depression by reducing their level of inflammatory cytokines in peripheral blood.

Abstract Background Novel molecular biomarkers for the risk assessment and early detection of coronary heart disease (CHD) are urgently needed for disease prevention. Altered methylation of ATP-binding cassette subfamily G member 1 (ABCG1) has been implicated in CHD but was mostly studied in Caucasians. Exploring the potential relationship between ABCG1 methylation in blood and CHD among the Chinese population would yield valuable insights. Methods Peripheral blood samples were obtained from a case–control study (287 CHD patients vs. 277 controls) and a prospective nested case–control study (171 CHD patients and 197 matched controls). DNA extraction and bisulfite-specific PCR amplification techniques were employed for sample processing. Quantitative assessment of methylation levels was conducted using mass spectrometry. Statistical analyses involved the utilization of logistic regression and nonparametric tests. Results We found hypomethylation of ABCG1 in whole blood was associated with the risk of CHD in both studies, which was enhanced in heart failure (HF) patients, female and younger subjects. When combined with baseline characteristics, altered ABCG1 methylation showed improved predictive effect for differentiating CHD cases, ischemic cardiomyopathy (ICM) cases, younger than 60 years CHD cases, and female CHD cases from healthy controls (area under the curve (AUC) = 0.68, 0.71, 0.74, and 0.73, respectively). Conclusions We demonstrated a robust link between ABCG1 hypomethylation in whole blood and CHD risk in the Chinese population and provided novel evidence indicating that aberrant ABCG1 methylation in peripheral blood can serve as an early detection biomarker for CHD patients.

Abstract Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children (n = 19) during acute virus-associated exacerbations and later during convalescence. Systems level analyses were employed to identify coexpression networks and infer the drivers of these networks, and validation was subsequently obtained via independent samples from asthmatic children. During exacerbations, PBMC exhibited significant changes in immune cell abundance and upregulation of complex interlinked networks of coexpressed genes. These were associated with priming of innate immunity, inflammatory and remodelling functions. We identified activation signatures downstream of bacterial LPS, glucocorticoids and TGFB1. We also confirmed that LPS binding protein was upregulated at the protein-level in plasma. Multiple gene networks known to be involved positively or negatively in asthma pathogenesis, are upregulated in circulating PBMC during acute exacerbations, supporting the hypothesis that systemic pre-programming of potentially pathogenic as well as protective functions of circulating immune cells preceeds migration into the airways. Enhanced sensitivity to LPS is likely to modulate the severity of acute asthma exacerbations through exposure to environmental LPS.

ABSTRACTThe crucial function of circulating microbial DNA (cmDNA) in peripheral blood is gaining recognition because of its importance in normal physiology and immunity in healthy individuals. Evidence suggests that cmDNA in peripheral blood is derived from highly abundant, translocating gut microbes. However, the associations with and differences between cmDNA in peripheral blood and the gut microbiome remain unclear. We collected blood, urine, and fecal samples from volunteers to compare their microbial information via 16S rDNA sequencing. The results revealed that, compared with gut microbial DNA, cmDNA in peripheral blood was associated with reduced diversity and a distinct microbiota composition. The cmDNA in the blood reflects the biochemical processes of microorganisms, including synthesis, energy conversion, degradation, and adaptability, surpassing that of fecal samples. Interestingly, cmDNA in blood showed a limited presence of DNA from anaerobes and gram-positive bacteria, which contrast with the trend observed in fecal samples. Furthermore, analysis of cmDNA revealed traits associated with mobile elements and potential pathologies, among others, which were minimal in stool samples. Notably, cmDNA analysis indicated similarities between the microbial functions and phenotypes in blood and urine samples, although greater diversity was observed in urine samples. Source Tracker analysis suggests that gut microbes might not be the main source of blood cmDNA, or a selective mechanism allows only certain microbial DNA into the bloodstream. In conclusion, our study highlights the composition and potential functions associated with cmDNA in peripheral blood, emphasizing its selective presence; however, further research is required to elucidate the mechanisms involved.IMPORTANCEOur research provides novel insights into the unique characteristics and potential functional implications of circulating microbial DNA (cmDNA) in peripheral blood. Unlike other studies that analyzed sequencing data from fecal or blood microbiota in different study cohorts, our comparative analysis of cmDNA from blood, urine, and fecal samples from the same group of volunteers revealed a distinct blood-specific cmDNA composition. We discovered a decreased diversity of microbial DNA in blood samples compared to fecal samples as well as an increased presence of biochemical processes microbial DNA in blood. Notably, we add to the existing knowledge by documenting a reduced abundance of anaerobes and gram-positive bacteria in blood compared to fecal samples according to the analysis of cmDNA and gut microbial DNA, respectively. This observation suggested that a potential selective barrier or screening mechanism might filter microbial DNA molecules, indicating potential selectivity in the translocation process which contrasts with the traditional view that cmDNA primarily originates from random translocation from the gut and other regions. By highlighting these differences, our findings prompt a reconsideration of the origin and role of cmDNA in blood circulation and suggest that selective processes involving more complex biological mechanisms may be involved.

Abstract The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.

Objectives: The mitochondrial DNA (mtDNA) is unique and circular with multiple copies of the genome. The lower mtDNA copy number (mtDNA-CN) in leukocytes is associated with the risk of all-cause mortality. However, its long-term association is unknown. Thus, the study examined the association between mtDNA-CN and the risk of all-cause mortality in a long-term follow-up study in the Japanese population. Design: This longitudinal study included the study cohort from an annual, population-based health checkup in the town of Yakumo, Hokkaido, Japan. Setting and Participants: 814 participants (baseline age range: 38–80 years, mean: 56.3 years) were included in this study in 1990. They were followed-up regarding mortality for about 30 years (median: 28.1 years) till 2019. Measures: The genomic DNA was extracted from peripheral blood mononuclear cells and the mtDNA-CN was measured using real-time polymerase chain reaction. The level of the mtDNA-CN was divided into tertiles (low, middle, and high). The participants were categorized based on their age into middle-aged (

Abstract Background Peripheral blood‐derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic effector function of PBNK cells and improving NK cell expansion in vitro for a convenient allogeneic therapy are essential. Materials and Methods Pure cytokine activation and expansion of NK cells (super NK [SNK]) from peripheral blood mononuclear cells were studied. Markers of activated and inhibited NK cells and cytokine secretion by NK cells were examined using flow cytometry. NK cell antitumor activity in vitro was assessed using lactate dehydrogenase (LDH) cytotoxicity assay and an Incucyte real‐time imaging system. Additionally, the function of SNK cells against ascites caused by ovarian cancer in NOD‐Prkdc(em26Cd52)il2rg(em26Cd22)/Nju (NCG) mice was determined. In a further investigation of the differences between PBNK and SNK, the mRNA of both cells was sequenced and analyzed. Results Human peripheral blood mononuclear cells showed selective NK cell expansion upon cytokine activation and culture. Both SNK and PBNK cells expressed activation markers, but at different levels, and SNK cells secreted more cytokines related to cytotoxicity than PBNK cells did. Accordingly, SNK cells exhibited strong antitumor activity ex vivo and improved NCG mice survival after intraperitoneal ovarian cancer transplantation. Mechanistically, SNK cells expressed more genes associated with nucleotide metabolism, fatty acid, and ATP metabolism than PBNK cells. Conclusion SNK cells derived from peripheral blood mononuclear cells have sufficiently activated mature characteristics and high antitumor activity, rendering them a highly promising and essential therapeutic approach for cancer treatment.

ABSTRACT This study aims to assess the usefulness of peripheral blood metagenomic next-generation sequencing (mNGS) in diagnosing invasive mucormycosis (IM). We conducted a retrospective analysis of clinical data from 73 patients with mucorales sequences detected by peripheral blood mNGS at the First Affiliated Hospital, Zhejiang University School of Medicine, between February 2021 and December 2022. We examined data on risk factors, clinical symptoms, imaging characteristics, pathogenic findings, clinical diagnoses, and treatment outcomes. Among the 73 patients with mucorales sequences detected by peripheral blood mNGS, 7 cases were confirmed, 12 were probable, 34 were possible, and 20 were false positives, based on the diagnostic criteria for IM. Among the 34 possible cases, patients exhibited risk factors, clinical symptoms, imaging features, and prognoses consistent with IM. In 7 out of the 12 probable cases, the same mucorale nucleic acid was found in peripheral blood mNGS samples collected at an average interval of 8.1 days. In the remaining 20 patients, mucorales nucleic acid was detected in peripheral blood mNGS, but they lacked risk factors or clinical features of mucorales infection and lacked other pathological evidence, leading to a judgment of false positive. The positive predictive value of peripheral blood mNGS for diagnosing invasive mucormycosis in the cases studied was 72.6%. Peripheral blood mNGS testing provides valuable insights for diagnosing invasive mucormycosis. However, it should be used in conjunction with risk factors, clinical features, and other pathogenic test results to make a comprehensive assessment. IMPORTANCE Given the high fatality rates, prompt and accurate identification of the fungal culprit is crucial, emphasizing the need for invasive mucormycosis. Unfortunately, mucormycosis lacks definitive biomarkers, depending primarily on smears, cultures, or pathology, all necessitating invasive specimen collection from the infection site. However, obtaining valid specimens early in critically ill patients poses substantial risks and challenges. Whether peripheral blood metagenomic next-generation sequencing (mNGS) can enhance early mucormycosis diagnosis, especially when direct specimen collection from the infection site is challenging, is warranted. This is a large-scale clinical study conducted to evaluate the utility and clinical impact of mNGS of peripheral blood for the diagnosis of invasive mucormycosis. We believe our study provided both novelty in translational medicine and a great value for the medical community to understand the strengths and limitations of mNGS of peripheral blood as a new diagnostic tool for the diagnosis and management of invasive mucormycosis.

Background: Our understanding of epigenetic modifications in the inner ear is very limited. Although epigenetic regulation of genes related to individual organ- and system-limited pathologies are generally expected to be tissue-specific, DNA methylation patterns in peripheral blood (PB) are found to be associated with the presence of several diseases with no typical hematological involvement. Here, we aimed to investigate whether there is a correlation between hearing-related genes' promoter region methylation in the PB samples with the presence of non-syndromic sensorineural hearing loss (NSSHL) with an aim of future utilization of DNA methylation as biomarkers in hearing loss. The study included 26 patients with NSSHL and a control group of 20 healthy individuals. CpG islands in the promoter regions of the GJB-2, GJB-6, and SLC24A genes were analyzed using bisulfite sequencing, and methylation percentages were analyzed. Results: Methylation levels at the 1st region of GJB-6 and the 1st and the 4th regions of SLC26A4 were found to differ significantly (p = 0.039, p = 0.042, and p = 0.029, respectively) between the patients and the control group. There was no statistically significant difference in methylation percentages of GJB-2 promoters. We also found that parents' consanguinity determines the methylation levels in patients' families. Conclusions: According to our knowledge, this is the first study that investigates epigenetic changes in the PB of patients with NSSHL. Despite the small sample size, our findings indicate that DNA methylation patterns in the PB could be of use for understanding epigenetic changes in the inner ear and the clinical management of NSSHL. [ABSTRACT FROM AUTHOR]

Background: Inflammation is a recognized factor in cancer progression and resistance to treatments. Several studies correlated inflammation-related peripheral blood inflammatory biomarkers (PBIB) to disease progression and poor survival in various cancer types and different populations. Nonetheless, inflammation is affected by the distinctive characteristics and environmental exposure of each population. There is no prior study addressing the association of pre-treatment inflammatory markers with outcomes in patients with breast cancer (BC) from Saudi Arabia. In this study, we evaluated the prognosis of locally advanced breast cancer (LABC) in relation to several PBIB. Materials and Methods: We retrospectively analyzed the data of female patients with LABC undergoing neoadjuvant chemotherapy (NACT). Demographics, body mass index (BMI), clinicopathologic characteristics and stage of the tumor, follow-up status, and response to treatment were collected. Outcomes were evaluated in relation to pre-treatment peripheral blood indices that were grouped based on the local laboratory cutoff values. Objective response rate (ORR) was predefined and assessed according to the post-NACT magnetic resonance imaging (MRI) breast and subcategorized into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Results: A total of 172 female patients with BC met the eligibility criteria from January 2014 to December 2019. The mean age at diagnosis was 53.4 ± 11, and BMI was 31.2 ± 6. Left BC accounted for 54.7%, and the majority was invasive ductal carcinoma (85.5%), moderately differentiated (51%), stage III (AJCC 8th edition) (73%), and estrogen receptor (ER)-positive tumor (79.1%). Human epidermal growth factor receptor 2 (HER2)-positive BC was reported in 32% and triple-negative breast cancer (TNBC) in 10%. Radiologic CR accounted for the majority of ORR (71.5%). Higher percentage of patients with normal red cell distribution width (RDW) of red blood cell (RBC) and low neutrophil–lymphocyte ratio (NLR) had CR with a significant P value of 0.003 and 0.014, respectively. Conclusion: Among several peripheral blood indices, RDW and NLR significantly influenced ORR. They can be explored further to potentially predict response after systemic therapy in patients with LABC. The great advantage of these biomarkers stems from their availability and affordability in routine clinical practice. [ABSTRACT FROM AUTHOR]

T cells' function and activation and the immunosuppressive effect of regulatory T cells (Tregs) play a pivotal role in the occurrence and progression of acute myeloid leukemia (AML). In this study, we investigate the expression of T cell activation markers and quantity of Tregs in bone marrow (BM) and peripheral blood (PB) from AML patients and further characterized their correlation with BM leukemic blasts. Expression of CD25, CD38, CD69, and HLA-DR on the surfaces of CD4+ and CD8+ T cells and the quantity of Tregs in BM and PB from new diagnosed (ND), relapsed-refractory (RR), complete remission (CR) AML patients were measured via flow cytometry. Compared to normal controls (NC), we found higher proportion of CD4+ CD69+ T cells, CD8+ CD69+ T cells and Tregs in PB. CD8+ CD38+ T cells and CD8+ HLA-DR+ T cells in RR were significantly higher than ND, CR and NC). Tregs were normalized when AML patients achieved CR. Moreover, there was a minor positive correlation between AML blasts and CD8+ CD25+ T cells or Tregs, while AML blasts had a minor negative correlation with CD4+ CD69+ T cells. Abnormal activation markers of T cells and Tregs may be involved in the pathological mechanism of ND and RR AML. Our results indicated that CD8+ CD38+ T cells and CD8+ HLA-DR+ T cells might be RR markers of AML patients. Furthermore, Tregs could be used as clinical indicators to evaluate prognosis for AML patients. [ABSTRACT FROM AUTHOR]

Aim: Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease with limited therapeutic options. A key factor limiting the development of effective therapeutics is the lack of disease biomarkers. We sought to assess whether biomarkers for diagnosis, prognosis or cohort stratification could be identified by RNA sequencing (RNA‐seq) of ALS patient peripheral blood. Methods: Whole blood RNA‐seq data were generated for 96 Australian sporadic ALS (sALS) cases and 48 healthy controls (NCBI GEO accession GSE234297). Differences in sALS–control gene expression, transcript usage and predicted leukocyte proportions were assessed, with pathway analysis used to predict the activity state of biological processes. Weighted Gene Co‐expression Network Analysis (WGCNA) and machine learning algorithms were applied to search for diagnostic and prognostic gene expression patterns. Unsupervised clustering analysis was employed to determine whether sALS patient subgroups could be detected. Results: Two hundred and forty‐five differentially expressed genes were identified in sALS patients relative to controls, with enrichment of immune, metabolic and stress‐related pathways. sALS patients also demonstrated switches in transcript usage across a small set of genes. We established a classification model that distinguished sALS patients from controls with an accuracy of 78% (sensitivity: 79%, specificity: 75%) using the expression of 20 genes. Clustering analysis identified four patient subgroups with gene expression signatures and immune cell proportions reflective of distinct peripheral effects. Conclusions: Our findings suggest that peripheral blood RNA‐seq can identify diagnostic biomarkers and distinguish molecular subtypes of sALS patients however, its prognostic value requires further investigation. [ABSTRACT FROM AUTHOR]

Background. Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC. Aims. To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease. Methods. Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results. Results. There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017). Conclusion. CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are crucial to the innate immune response. They regulate inflammatory reactions by initiating the production of pro-inflammatory cytokines and chemokines. TLRs also play a role in shaping the adaptive immune responses. While this protective response is important for eliminating infectious pathogens, persistent activation of TLRs may result in chronic immune activation, leading to detrimental effects. The role of TLR2 in regulating HIV-1 infection in vivo has yet to be well described. In this study, we used an SIV-infected rhesus macaque model to simulate HIV infection in humans. We evaluated the plasma of the macaques longitudinally and found a significant increase in the soluble TLR2 (sTLR2) level after SIV infection. We also observed an increase in membrane-bound TLR2 (mb-TLR2) in cytotoxic T cells, B cells, and NK cells in PBMC and NK cells in the gut after infection. Our results suggest that sTLR2 regulates the production of various cytokines and chemokines, including IL-18, IL-1RA, IL-15, IL-13, IL-9, TPO, FLT3L, and IL-17F, as well as chemokines, including IP-10, MCP-1, MCP-2, ENA-78, GRO-α, I-TAC, Fractalkine, SDF-1α, and MIP-3α. Interestingly, these cytokines and chemokines were also upregulated after the infection. The positive correlation between SIV copy number and sTLR2 in the plasma indicated the involvement of TLR2 in the regulation of viral replication. These cytokines and chemokines could directly or indirectly regulate viral replication through the TLR2 signaling pathways. When we stimulated PBMC with the TLR2 agonist in vitro, we observed a direct induction of various cytokines and chemokines. Some of these cytokines and chemokines, such as IL-1RA, IL-9, IL-15, GRO-α, and ENA-78, were positively correlated with sTLR2 in vivo, highlighting the direct involvement of TLR2 in the regulation of the production of these factors. Our findings suggest that TLR2 expression may be a target for developing new therapeutic strategies to combat HIV infection. [ABSTRACT FROM AUTHOR]

Functional activity of the blood system was studied in two migratory Ural species, Vespertilio murinus Linnaeus, 1758 and Pipistrellus nathusii Keyserling et Blasius, 1839. A multivariate nonparametric ANOVA of red blood parameters showed significant interspecific differences (p < 0.05) between the migrating bats and the resident species pond bat. A certain genetically determined multidirectionality in the mobilization of emergency regulation mechanisms of the lymphoid blood system was observed in bats. [ABSTRACT FROM AUTHOR]

To investigate the expression of Siglec10 and CD24 in normal early pregnancy and missed abortion, and their significance in the maternal-fetal interface. For our research, we employed Q-PCR and WB techniques to evaluate the traits and expression of Siglec10 and CD24 in the nonpregnant endometrium, as well as in the villus and decidua of women in their 6–10 weeks of normal early pregnancy and those who experienced missed abortion. Additionally, we utilized ELISA to determine the levels of Siglec10 and CD24 in the peripheral blood of pregnancy, missed abortion, and non-pregnant individuals. T-test and ANOVA were used to compare groups. 1. Villous tissues in early pregnancy showed high expression of Siglec10 and CD24, with a significant increase in expression in the missed abortion group (P < 0.01). 2. Nonpregnant endometrial tissue showed low expression of Siglec10 and CD24, while early pregnancy decidua showed high expression, with even higher expression in missed abortion (all P < 0.05). 3. Serum levels of Siglec10 and CD24 in normal early pregnancy were significantly higher than non-pregnancy (P < 0.01). However, the missed abortion group showed significantly higher levels than normal pregnancy (P < 0.01). 4. CD24 expression in serum of missed abortion increases with Siglec10 expression, indicating a significant positive correlation (r = 0.500, P < 0.01). Siglec10 and CD24 expression in villus, decidua, and peripheral blood are up-regulated in unexplained missed abortions than those of women with normal pregnancies. This suggests that the levels of serum Siglec10 and CD24 can be used as an effective predictor of missed abortion. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most common malignant brain tumor and has "immunologically cold" features. Changing GBM to an "immunologically hot" tumor requires a strong trigger that induces initial immune responses in GBM. Allogeneic natural killer cells (NKCs) have gained considerable attention as promising immunotherapeutic tools against cancer, where gene-edited NKCs would result in effective anti-cancer treatment. The present study focused on the immune checkpoint molecule cytokine-inducible SH2-containing protein (CISH, or CIS) as a critical negative regulator in NKCs. Methods: The GBM tumor environment featured with immunological aspect was analyzed with Cancer immunogram and GlioVis. We generated human primary CIS-deleted NKCs (NK dCIS) using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) with single guide RNA targeting genome sites on CIS coding exons. The genome-edited NKCs underwent microarray with differential expression analysis and gene set enrichment analysis (GSEA). The anti-GBM activity of the genome-edited NKCs was evaluated by apoptosis induction effects against allogeneic GBM cells and spheroids. We further detected in vivo antitumor effects using xenograft brain tumor mice. Results: We successfully induced human CIS-deleted NKCs (NK dCIS) by combining our specific human NKC expansion method available for clinical application and genome editing technology. CIS gene-specific guide RNA/Cas9 protein complex suppressed CIS expression in the expanded NKCs with high expansion efficacy. Comprehensive gene expression analysis demonstrated increased expression of 265 genes and decreased expression of 86 genes in the NK dCIS. Gene set enrichment analysis revealed that the enriched genes were involved in NKC effector functions. Functional analysis revealed that the NK dCIS had increased interferon (IFN)ɤ and tumor necrosis factor (TNF) production. CIS deletion enhanced NKC-mediated apoptosis induction against allogeneic GBM cells and spheroids. Intracranial administration of the allogeneic NKCs prolonged the overall survival of xenograft brain tumor mice. Furthermore, the NK dCIS extended the overall survival of the mice. Conclusion: The findings demonstrated the successful induction of human primary NK dCIS with CRISPR/Cas9 with efficient expansion. CIS deletion enhanced the NKC-mediated anti-tumor effects in allogeneic GBM and could be a promising immunotherapeutic alternative for patients with GBM. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there any methylome alteration in women with PCOS who were diagnosed using the new international evidence-based guidelines? SUMMARY ANSWER A total of 264 differentially methylated probes (DMPs) and 53 differentially methylated regions (DMRs) were identified in patients with PCOS and healthy controls. WHAT IS KNOWN ALREADY PCOS is a common endocrine disorder among women of reproductive age and polycystic ovarian morphology (PCOM) is one of the main features of the disease. Owing to the availability of more sensitive ultrasound machines, the traditional diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is currently debated as there is a risk of overdiagnosis. The new international evidence-based guidelines set the threshold for PCOM as ≥20 antral follicles per ovary when using endovaginal ultrasound transducers with a frequency bandwidth that includes 8 MHz. However, current DNA methylation studies in PCOS are still based on the Rotterdam criteria. This study aimed to explore aberrant DNA methylation in patients diagnosed with PCOS according to the new evidence-based guidelines. STUDY DESIGN, SIZE, DURATION This cross-sectional case–control study included 34 PCOS cases diagnosed using new international evidence-based guidelines and 36 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 70 women, including 34 PCOS cases and 36 controls, were recruited. DNA extracted from whole blood samples of participants were profiled using array technology. Data quality control, preprocessing, annotation, and statistical analyses were performed. Least absolute shrinkage and selection operator (LASSO) regression were used to build a PCOS diagnosis model with DNA methylation sites. MAIN RESULTS AND THE ROLE OF CHANCE We identified 264 DMPs between PCOS cases and controls, which were mainly located in intergenic regions or gene bodies of the genome, CpG open sea sites, and heterochromatin of functional elements. Pathway enrichment analysis showed that DMPs were significantly enriched in biological processes involved in triglyceride regulation. Three of these DMPs overlapped with the PCOS susceptibility genes thyroid adenoma-associated protein (THADA), aminopeptidase O (AOPEP), and tripartite motif family-like protein 2 (TRIML2). Fifty-three DMRs were identified and their annotated genes were largely enriched in allograft rejection, thyroid hormone production, and peripheral downstream signaling effects. Two DMRs were closely related to the PCOS susceptibility genes, potassium voltage-gated channel subfamily A member 4 (KCNA4) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1). Finally, based on LASSO regression, we built a methylation marker model with high accuracy for PCOS diagnosis (AUC=0.952). LIMITATIONS, REASONS FOR CAUTION The study cohort was single-center and the sample size was relatively limited. Further analyses with a larger number of participants are required. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to identify DNA methylation alterations in women with PCOS diagnosed using the new international evidence-based guideline, and it provided new molecular insight into the application of the new guidelines. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (2021YFC2700400), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (32370916, 82071606, 82101707, 82192874, and 31871509), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objective: To assess whether endometriosis (EMs) was related to systematic and/or local deviations of cluster of differentiation (CD)4 + T cells. Methods: Until November 2022, we enrolled a total of 1363 EMs and 1564 healthy women from 32 studies who met the inclusion criteria. Results: After systematically retrieving the literature, we identified 1086 citations and 32 case–control studies were enrolled. Cumulative results suggested that there were insignificant deviations of CD4 + T cells during peripheral blood (PB) between EMs and healthy women (RR: − 0.83, I2 = 99%, p = 0.65), also no statistically significant difference was found between mild and severe EMs (RR: 3.19, I2 = 94%, p = 0.19). We also found insignificant deviations of CD4 + /CD8 + during PB between EMs and healthy women (RR: 0.09, I2 = 99%, p = 0.39), and between mild and severe EMs (RR: − 0.16, I2 = 99%, p = 0.29). The results might suggest that there was no significant correlation between EMs and systematic deviations of CD4 + T cells. When it came to local deviation during peritoneal fluid (PF), the polled results suggested that the frequency of CD4 + T cells during EMs was significantly lower than healthy women (RR: − 5.38, I2 = 93%, p = 0.01), and the ratio of CD4 + /CD8 + during EMs was significantly lower than healthy women (RR: − 0.13, I2 = 0%, p < 0.0001). However, there were insignificant deviations of CD4 + during PF between mild and severe EMs (RR: 1.65, I2 = 53%, p = 0.15), also there was an insignificant difference of CD4 + /CD8 + between mild and severe EMs (RR: − 0.09, I2 = 14%, p = 0.19). EMs might be closely related to local deviations of CD4 + T cells. Conclusion: There was no obvious correlation between EMs and systematic deviations of CD4 + T cells, EMs might be closely related to local deviations of CD4 + T cells. Further study on the functional deviations and subpopulation distribution of CD4 + T cells is urgently needed. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) therapies, that is, using monoclonal antibodies to reinvigorate tumor-reactive, antigen-specific T cells from the inhibitory effects of CTLA-4, PD-1 and PD-L1 immune checkpoints, have revolutionized the therapeutic landscape of modern oncology. However, only a subset of patients can benefit from the ICB therapy. Biomarkers associated with ICB response, resistance and prognosis have been subjected to intensive research in the past decade. Early studies focused on the analysis of tumor specimens and their residing microenvironment. However, biopsies can be challenging to obtain in clinical practice, and do not reflect the dynamic changes of immunological parameters during the ICB therapy. Recent studies have investigated profiles of antigen-specific T cells derived from the peripheral compartment using multi-omics approaches. By tracking the clonotype and diversity of tumor-reactive T cell receptor repertoire, these studies collectively establish that de novo priming of antigen-specific T cells in peripheral blood occurs throughout the course of ICB, whereas preexisting T cells prior to ICB are exhausted to various degrees. Here, we review what is known about ICB-induced T cell phenotypic and functional changes in cancer patients both within the tumor microenvironment and in the peripheral compartment. A better understanding of parameters influencing the response to ICBs will provide rationales for developing novel diagnostics and combinatorial therapeutic strategies to maximize the clinical efficacies of ICB therapies. [ABSTRACT FROM AUTHOR]

Although some studies have reported on the levels and clinical significance of peripheral blood neutrophil/lymphocyte ratio (NLR) in cervical cancer, the role of NLR levels and their changes preoperatively and postoperatively in early cervical cancer remain unclear. Our analyses explored the preoperative and postoperative NLR in 203 patients with stage I-IIA cervical cancer and evaluated the relationship between NLR changes, clinicopathological characteristics, and patient prognosis. The cut-off preoperative and postoperative NLR values were determined using receiver operating characteristic curve analysis. Preoperative NLR correlated with age, menopausal status, tumor size, and vascular infiltration, whereas postoperative NLR correlated with tumor differentiation. Patients with cervical cancer with a high preoperative NLR had significantly shorter overall survival (OS) and progression-free survival (PFS) than other patients, whereas PFS was significantly lower in the high postoperative NLR group. When comparing postoperative and preoperative NLR values, we observed a significantly higher rate of increase in postmenopausal patients and those without vascular infiltration than that among premenopausal patients and those with vascular infiltration. However, no clear difference in prognosis was observed between the groups with increased and decreased NLR. Therefore, a high peripheral blood NLR may predict a poor prognosis in patients with early cervical cancer. The effect of NLR changes on the prognosis of patients with cervical cancer requires further verification in multicenter studies. [ABSTRACT FROM AUTHOR]

The problem of identifying the sensitivity of living organisms to ionizing irradiation remains relevant, considering the spread of anthropogenic environmental pollution. The study on the effect of single X-ray irradiation (1,5 Gy) on peripheral blood of bank voles (Myodes glareolus (Schreber, 1780)) captured within territories with background radiation level was conducted. Hematological indicators, characterizing the overall condition of performance of the body, were determined dynamically on the first and seventh days after exposure to detect both early changes and the rate of recovery processes. The patterns and features of the main components of leukocyte formula found in peripheral blood of irradiated animals are being discussed. Differences between irradiated and control mouse-like rodents are shown, using parameters of erythrocytes and leukocytes. The analysis of changes in the peripheral blood of irradiated bank voles indicates the high reserve capacity of the body, according to its ability to restore homeostasis. [ABSTRACT FROM AUTHOR]

Objective To explore the role of miR-34a methylation in the development of gastric cancer,and explore the correlation of miR-34a methylation with gastric cancer, pathological features and Helicobacter pylori(HP)infection. Methods The methylation level of miR-34a gene CpG island of thirty-one gastric cancer patients and tweenty-four healthy people were detected by matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry(MALDI-TOF MS)technique. Results The overall average methylation level of miR-34a was higher in gastric cancer than that in the control, the average methylation of miR-34a CpG_5,CpG_12.13 was significantly higher in the gastric cancer group than they were in the control group(51.7%±5.9% vs. 37.8%±7.8%,84.61%±8.2% vs. 68.1%±12.1%,P＜0.01).The methylation level of miR-34a CpG_5 in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group (53.55%±4.86% vs. 47.22%±6.07%,P＜0.01),and the methylation of CpG_5 in TNM stage (stage Ⅱ + stage Ⅲ) was higher than that in stage Ⅰ(53.21%±4.8% vs. 46.57%±6.9%, P＜0.05). Conclusions The miR-34a methylation is potentially associated with the occurrence and development of gastric cancer. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is an inflammatory bowel disease that is characterized by chronic inflammation of digestive system and has a nickname "green cancer" because of its sustained alternation of periods of flares and remissions. Here, we investigated the inflammation changes in peripheral blood system of CD patients, which are less reported in China. Peripheral blood samples of 167 CD patients and 30 healthy people, as well as their clinical information, were collected at the Second Affiliated Hospital of Soochow University. Flow cytometry was performed to analyze the ratio of CD4 T cells to CD8 T cells. Cytometric Bead Array kit was used to detect the cytokines in peripheral blood in CD patients. Moreover, the expression of inflammasomes was also detected by RT-PCR. The percentage and cell number of lymphocytes in CD patients' peripheral blood system decreased significantly, while monocytes increased remarkably. Interestingly, there was an inversion of the CD4 T cells/CD8 T cells ratio in peripheral blood of CD patients. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) increased significantly in CD patients' peripheral blood, and lipopolysaccharide (LPS) stimulation aggravate inflammatory response. In addition, the expression of nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1 (NLRP1) and NLRP3 in peripheral blood mononuclear cells (PBMC) of CD patients increased significantly after LPS stimulation. The inflammation in peripheral blood of CD patients had significant changes, including PBMC, cytokines and inflammasomes. These results are helpful to get a deeper understanding of CD and improve the efficiency of diagnosis and treatment in China. [ABSTRACT FROM AUTHOR]

Over the last years, the use of peripheral blood-derived big datasets in combination with machine learning technology has accelerated the understanding, prediction, and management of pulmonary and critical care conditions. The goal of this article is to provide readers with an introduction to the methods and applications of blood omics and other multiplex-based technologies in the pulmonary and critical care medicine setting to better appreciate the current literature in the field. To accomplish that, we provide essential concepts needed to rationalize this approach and introduce readers to the types of molecules that can be obtained from the circulating blood to generate big datasets; elaborate on the differences between bulk, sorted, and single-cell approaches; and the basic analytical pipelines required for clinical interpretation. Examples of peripheral blood-derived big datasets used in recent literature are presented, and limitations of that technology are highlighted to qualify both the current and future value of these methodologies. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What are the dynamic expression features of plasma microRNAs (miRNAs) during the peri-implantation period in women with successful pregnancy via single frozen-thawed blastocyst transfer? SUMMARY ANSWER There is a significant change in the plasma miRNA expression profile before and after blastocyst transfer, during the window of implantation. WHAT IS KNOWN ALREADY The expression of miRNAs in peripheral blood has indicative functions during the peri-implantation period. Nevertheless, the dynamic expression profile of circulating miRNAs during the peri-implantation stage in women with a successful pregnancy has not been studied. STUDY DESIGN, SIZE, DURATION Seventy-six women treated for infertility with a single frozen-thawed blastocyst transfer in a natural cycle were included in this study. Among them, 57 women had implantation success and a live birth, while 19 patients experienced implantation failure. Peripheral blood samples were collected at five different time points throughout the peri-implantation period, including D0 (ovulation day), D3, D5, D7, and D9 in this cycle of embryo transfer. The plasma miRNAs in women with blastocyst transfer were isolated, sequenced, and analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS Peripheral blood samples were collected in EDTA tubes and stored at −80°C until further use. miRNAs were isolated from blood, cDNA libraries were constructed, and the resulting sequences were mapped to the human genome. The plasma miRNAs were initially analyzed in a screening cohort (n = 34) with successful pregnancy. Trajectory analysis, including a global test and pairwise comparisons, was performed to detect dynamic differentially expressed (DE) miRNAs. Fuzzy c-means clustering was conducted for all dynamic DE miRNAs. The correlation between DE miRNAs and clinical characteristics of patients was investigated using a linear mixed model. Target genes of the miRNAs were predicted, and functional annotation analysis was performed. The expression of DE miRNAs was also identified in a validation set consisting of women with successful (n = 23) and unsuccessful (n = 19) pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE Following small RNA sequencing, a total of 2656 miRNAs were determined as valid read values. After trajectory analysis, 26 DE miRNAs (false discovery rate < 0.05) were identified by the global test, while pairwise comparisons in addition identified 20 DE miRNAs. A total of seven distinct clusters representing different temporal patterns of miRNA expression were discovered. Nineteen DE miRNAs were further identified to be associated with at least one clinical trait. Endometrium thickness and progesterone level showed a correlation with multiple DE miRNAs (including two of the same miRNAs, hsa-miR-1-3p and hsa-miR-6741-3p). Moreover, the 19 DE miRNAs were predicted to have 403 gene targets, and there were 51 (12.7%) predicted genes likely involved in both decidualization and embryo implantation. Functional annotation for predicted targets of those clinically related DE miRNAs suggested the involvement of vascular endothelial growth factor and Wnt signaling pathways, as well as responses to hormones, immune responses, and cell adhesion-related signaling pathways during the peri-implantation stage. LARGE SCALE DATA The raw miRNA sequence data reported in this article have been deposited in the Genome Sequence Archive (GSA-Human: HRA005227) and are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human/browse/HRA005227. LIMITATIONS, REASONS FOR CAUTION Although the RNA sequencing results revealed the global dynamic changes of miRNA expression, further experiments examining the clinical significance of the identified DE miRNAs in embryo implantation outcome and the relevant regulatory mechanisms involved are warranted. WIDER IMPLICATIONS OF THE FINDINGS Understanding the dynamic landscape of the miRNA transcriptome could shed light on the physiological mechanisms involved from ovulation to the post-implantation stage, as well as identifying biomarkers that characterize stage-related biological process. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Major clinical research project of Tangdu Hospital (2021LCYJ004) and the Discipline Platform Improvement Plan of Tangdu Hospital (2020XKPT003). The funders had no influence on the study design, data collection, and analysis, decision to publish, or preparation of the article. There are no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

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Idiopathic pulmonary fibrosis (IPF) represents a chronic progressive fibrotic interstitial lung disease of unknown cause with an ominous prognosis. It remains an unprecedent clinical challenge due to its delayed diagnosis and unpredictable clinical course. The need for accurate diagnostic, prognostic and predisposition biomarkers in everyday clinical practice becomes more necessary than ever to ensure prompt diagnoses and early treatment. The identification of such blood biomarkers may also unravel novel drug targets against IPF development and progression. So far, the role of diverse blood biomarkers, implicated in various pathogenetic pathways, such as in fibrogenesis (S100A4), extracellular matrix remodelling (YKL-40, MMP-7, ICAM-1, LOXL2, periostin), chemotaxis (CCL-18, IL-8), epithelial cell injury (KL-6, SP-A, SP-D), autophagy and unfolded protein response has been investigated in IPF with various results. Moreover, the recent progress in genetics in IPF allows for a better understanding of the underlying disease mechanisms. So far, the causative mutations in pulmonary fibrosis include mutations in telomere-related genes and in surfactant-related genes, markers that could act as predisposition biomarkers in IPF. The aim of this review is to provide a comprehensive overview from the bench to bedside of current knowledge and recent insights on biomarkers in IPF, and to suggest future directions for research. Large-scale studies are still needed to confirm the exact role of these biomarkers. [ABSTRACT FROM AUTHOR]

Bovine lymphosarcoma is one of the most prevalent neoplastic diseases in cattle, which affects both dairy and beef animals. Serological evidence and molecular characterization of Enzootic bovine leukemia are reported from India, but reporting of juvenile lymphosarcoma in the calf is scarce. A four-month-old female HF Cross calf with depression, progressive weight loss, weakness, and enlarged peripheral lymph nodes were brought for treatment to the Veterinary Clinical Complex (VCC), SKUASTJ, Jammu, R.S. Pura, India. Peripheral blood showed leukocytosis, lymphocytosis, and normocytic, normochromic anemia. Blood smear and cytopathological examinations revealed the presence of atypically large lymphocytes with obvious clear cytoplasmic vacuoles and cleaved, reniform, amoeboid nuclei with unclear nucleoli. Histopathological examination of the affected lymph nodes showed the presence of a tumor that was characterized by proliferating round, distinct pleomorphic cells having minimal cytoplasm, prominent nuclei, and oval and round basophilic shapes. On the basis of cytological and histo-pathological basis, the present case was described as sporadic juvenile lymphosarcoma.

Monocytes play an important role in the systemic immune defense against pathogens and maintaining physiological pregnancy. During pregnancy peripheral monocytes migrate into the decidua and form the pool of decidual macrophages which participate in the formation and development of placental tissues. The population of peripheral blood monocytes is phenotypically and functionally heterogeneous. In humans, there are different monocyte subsets depending on the expression of CD14 and CD16. CD56-positive monocytes are found in healthy women. Their number is positively correlated with body mass index, body fat. Tim-3 (T cell Ig and mucin domain-containing protein 3) expression is observed in peripheral monocytes during pregnancy. It is known that peripheral monocyte functions effectively change at pregnancy to form the immune tolerance at the maternal-fetal interface and the systemic immune defense against pathogens. However, the monocyte phenotype shift during pregnancy remain poorly understood. Therefore, the aim of the study was to evaluate the CD56 and Tim-3 expressions in monocyte subsets in human pregnancy. Peripheral blood mononuclear cells were isolated from peripheral blood of pregnant women (gestational age 29 weeks (28-31) by density gradient centrifugation and analyzed by flow cytometry. Peripheral blood of healthy non-pregnant fertile women (in follicular phase of the menstrual cycle) aged 21-29 years was studied as control. Pregnant women had a lower percentage of classical CD14hi/CD16- monocytes in comparison with non-pregnant. The percentages of intermediate (CD14hi/CD16+) and non-classical (CD14low/CD16+) monocytes did not change. The CD56 molecule expression was observed in all monocyte subsets in pregnant and non-pregnant women. Pregnant women had a higher percentage of CD56-positive classical (CD14hiCD16-) and non-classical (CD14lowCD16+) monocytes than non-pregnant. The percentage of CD56-positive intermediate (CD14hiCD16+) monocytes did not change. The percentages of double-positive CD56+Tim-3+ classical (CD14hiCD16-) and non-classical (CD14lowCD16+) monocytes were increased in pregnant women. The numbers of double-positive CD56+Tim-3+intermediate (CD14hiCD16+) monocytes did not change. Thus, the CD56 and Tim-3 expressions in different monocyte subsets were changed in human pregnancy.

Objective Neuroblastoma typically affects children within the first 5 years of life and accounts for 10% of all pediatric malignancies. Neuroblastoma at onset may manifest as a localized or metastatic illness. The aim of this study was to identify hematomorphological features in neuroblastoma infiltrating marrow as well as to ascertain the prevalence of bone marrow infiltration in neuroblastoma. Materials and Methods This retrospective study included newly diagnosed 79 cases of neuroblastoma, which were referred for bone marrow examination for the staging of the disease. Medical records were retrieved to acquire hematomorphological findings of peripheral blood and bone marrow smears. Statistical Package for Social Sciences, IBM Inc., USA, version 21.0 was used to analyze the data. Results The interquartile age range of neuroblastoma cases was 24.0 to 72.0 months (median = 48 months) with a male to female ratio of 2.7:1. Also, 55.6% (44/79) of cases in the study population showed evidence of marrow infiltration. The bone marrow infiltration was significantly linked to thrombocytopenia (p = 0.043) and nucleated red blood cells (p = 0.003) in peripheral blood. The bone marrow smears of cases with infiltration showed a significant shift to the left in the myeloid series (p = 0.001) and an increased number of erythroid cells (p = 0.001). Conclusion For neuroblastoma patients, a diligent, exhaustive search for infiltrating cells in bone marrow is advised if thrombocytopenia or nucleated red blood cells are identified on a peripheral blood smear and bone marrow smears showed myeloid left shift with an increased number of erythroid cells.

Abstract Objective At present, there is still a lack of reliable biomarkers for ovarian cancer (OC) to guide prognosis prediction and accurately evaluate the dominant population of immunotherapy. In recent years, the relationship between peripheral blood markers and tumor‐infiltrating immune cells (TICs) with cancer has attracted much attention. However, the relationship between the survival of OC patients and intratumoral‐ or extratumoral‐associated immune cells remains controversial. Methods In this study, four machine‐learning algorithms were used to predict overall survival in OC patients based on peripheral blood indicators. To further screen out immune‐related gene and molecular targets, we systematically explored the correlation between TICs and OC patient survival based on The Cancer Genome Atlas database. Using the TICs score method, patients were divided into a low immune infiltrating cell group and a high immune infiltrating cell group. Results The results showed that there was a significant statistical significance between the peripheral blood indicators and the survival prognosis of OC patients. Survival analysis showed that TICs play a crucial role in the survival of OC patients. Four core genes, CXCL9, CD79A, MS4A1, and MZB1, were identified by cross‐PPI and COX regression analysis. Further analysis found that these genes were significantly associated with both TICs and survival in OC patients. Conclusions These results suggest that both peripheral blood markers and TICs can be used as prognostic predictors in patients with OC, and CXCL9, CD79A, MS4A1, and MZB1 may be potential therapeutic targets for OC immunotherapy.

Yan Lin,1,&ast; Jiaoning Fang,1,&ast; Ruilan Ni,1,&ast; Li Zhang,1 Jie Zhao,1 Xiumin Jiang,2 Yuping Lin,2 Mian Pan1 1Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Nurse, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mian Pan, Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-13178031273 ; +86-591-86329321, Email panmian1973@126.com Xiumin Jiang, Department of Nurse, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Email jzc0427@163.comObjective: Cervical cerclage is an effective method to prevent preterm birth. However, the clinical indicators that can predict cervical cerclage remain limited. This study aimed to explore whether dynamically inflammatory markers are valuable biomarkers for the prognosis of cervical cerclage.Methods: This study included 328 participants. Inflammatory markers were calculated using maternal peripheral blood before and after the cervical cerclage procedure. The Chi-square test, linear regression, and logistic regression were performed to evaluate the dynamic change of inflammatory markers with the prognosis of cervical cerclage. And the optimal cut-off values of inflammatory markers were calculated.Results: Totally 328 pregnant women were analyzed in the study. 223 (67.99%) participants obtained successful cervical cerclage. This study revealed that the maternal age, the baseline BMI (cm2/kg), the times of gravida, the rate of recurrent abortion, the PPROM, cervical length shorter (< 1.5cm), cervical dilation (≥ 2cm), the bulging membrane, the Pre-SII, the Pre-SIRI, the Post-SII, the Post-SIRI, and the ΔSII were significantly associated with outcomes after cervical cerclage (all P< 0.05). Pre-SII, Pre-SIRI, Post-SII, Post-SIRI, and ΔSII levels were mainly related to maternal-neonatal outcomes. Furthermore, the results demonstrated that the ΔSII level had the highest OR (OR=14.560; 95% CI (4.461– 47.518)). In addition, we revealed that Post-SII and ΔSII levels had the highest AUC (0.845/0.840) and relatively higher sensitivity/specificity (68.57/92.83% and 71.43/90.58%) and PPV/ NPV (81.82/86.25% and 78.13/87.07%) compared with other indicators.Conclusion: This study suggested that the dynamic change of SII level and SIRI level are important biochemical markers to predict the prognosis of cervical cerclage and maternal-neonatal prognosis, especially the Post-SII and ΔSII levels. They can help to determine candidates for cervical cerclage before surgical procedure and enhance postoperative surveillance.Keywords: cervical cerclage, maternal-neonatal, outcome, inflammatory markers, peripheral blood

Abstract Background Acute type A aortic dissection (ATAAD) is a life-threatening pathological change of the aorta. Patients who have undergone aortic surgery are usually at high risk of mortality. Aim We investigated the predictive value of serum Mammalian sterile 20-like kinase 1 (MST1) as a biomarker for the risk of mortality of ATAAD patients. Methods In this retrospective cohort study, we analyzed 160 consecutive ATAAD patients who had undergone emergency surgery from July 2016 to April 2017. Medical records and blood samples were collected and analyzed. ELISA assays were performed to detect the concentrations of several proteins including MST1. The relationship between these potential biomarkers and the primary endpoint of death was evaluated using Cox proportional hazard regression analysis. Results Compared with a low level (