Number Of Peripheral Blood Leukocytes Research Articles

Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation.

CXCR4 is a key regulator of the development of NK cells and DCs, both of which play an important role in early placental development and immune tolerance at the maternal-fetal interface. However, the role of CXCR4 in pregnancy is not well understood. Our study demonstrates that adult-induced global genetic CXCR4 deletion, but not uterine-specific CXCR4 deletion, was associated with increased pregnancy resorptions and decreased litter size. CXCR4-deficient mice had decreased NK cells and increased granulocytes in the decidua, along with increased leukocyte numbers in peripheral blood. We found that CXCR4-deficient mice had abnormal decidual NK cell aggregates and NK cell infiltration into trophoblast areas beyond the giant cell layer. This was associated with low NK cell expression of granzyme B, a NK cell granule effector, indicative of NK cell dysfunction. Pregnancy failure in these mice was associated with abnormalities in placental vascular development and increased placental expression of inflammatory genes. Importantly, adoptive BM transfer of WT CXCR4+ BM cells into CXCR4-deficient mice rescued the reproductive deficits by normalizing NK cell function and mediating normal placental vascular development. Collectively, our study found an important role for maternal CXCR4 expression in immune cell function, placental development, and pregnancy maintenance.

Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis

To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC). Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota. Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora. Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.

High leukocyte mitochondrial DNA copy number contributes to poor prognosis in breast cancer patients

BackgroundCompelling evidence has indicated a significant association between leukocyte mitochondrial DNA copy number (mtDNAcn) and prognosis of several malignancies in a cancer-specific manner. However, whether leukocyte mtDNAcn can predict the clinical outcome of breast cancer (BC) patients has not been well investigated.MethodsThe mtDNA copy number of peripheral blood leukocytes from 661 BC patients was measured using a Multiplex AccuCopy™Kit based on a multiplex fluorescence competitive PCR principle. Kaplan–Meier curves and Cox proportional hazards regression model were applied to investigate the association of mtDNAcn with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer special survival (BCSS), and overall survival (OS) of patients. The possible mtDNAcn-environment interactions were also evaluated by the Cox proportional hazard regression models.ResultsBC patients with higher leukocyte mtDNA-CN exhibited a significantly worse iDFS than those with lower leukocyte mtDNAcn (5-year iDFS: fully-adjusted model: HR = 1.433[95%CI 1.038–1.978], P = 0.028). Interaction analyses showed that mtDNAcn was significantly associated with hormone receptor status (adjusted p for interaction: 5-year BCSS: 0.028, 5-year OS: 0.022), so further analysis was mainly in the HR subgroup. Multivariate Cox regression analysis demonstrated that mtDNAcn was an independent prognostic factor for both BCSS and OS in HR-positive patients (HR+: 5-year BCSS: adjusted HR (aHR) = 2.340[95% CI 1.163–4.708], P = 0.017 and 5-year OS: aHR = 2.446 [95% CI 1.218–4.913], P = 0.011).ConclusionsFor the first time, our study demonstrated that leukocyte mtDNA copy number might influence the outcome of early-stage breast cancer patients depending on intrinsic tumor subtypes in Chinese women.

Angelica Sinensis polysaccharide antagonizes 5-Fluorouracil-induced spleen injury and dysfunction by suppressing oxidative stress and apoptosis

Angelica Sinensis polysaccharide (ASP), the main active component of Angelica sinensis, possesses antioxidative and anti-apoptotic properties. In this study, we have investigated the antagonistic effect of ASP on 5-FU-induced injury of mouse spleen in vivo and splenocytes in vitro, and its possible mechanism. Our results showed that ASP inhibited 5-FU-induced decreases in spleen weight and organ index in mice, restored the number of peripheral blood leukocytes and lymphocytes, repaired spleen structure disorder and functional impairment, rescued serum IL-2, IL-6, and IFN-γ levels, and relieved 5-FU-induced mitochondrial swelling， reduced the oxidant accumulation including MDA and ROS, whereas increasing the activities of GSH, SOD and CAT. The mechanism may be related to ASP downregulation of Keap1 protein expression thus motivating the nuclear translocation of Nrf2. Furthermore, ASP alleviated the apoptosis of spleens in vivo and splenocytes in vitro, and reactivated PI3K / AKT signalling. In conclusion, the protective effect of ASP on spleens and splenocytes may be related to the reduction of oxidative stress and apoptosis via reactivation of Nrf2 and PI3K/AKT pathways. This study has provided a new protective agent for minimizing the spleen injury caused by 5-FU and a new idea for improving the prognosis of chemotherapy patients.

Leukocyte Response to Campylobacter Intra-Abdominal Infection in One Day Old Leghorn Chickens

Using a previously characterized and described abdominal model to define the avian immune response to Salmonella intra-abdominal challenge in chickens, we have adapted this technique for the study of chickens' immune response to a Campylobacter intra-abdominal challenge. The intra-abdominal Campylobacter infection model facilitates the characterization of peripheral blood leukocyte dynamics and abdominal cell infiltrates. Day-of-hatch Leghorn chickens were injected intra-abdominally (IA) with Campylobacter jejuni [(CJ)1 × 108 colony-forming units (CFUs)]. Changes in peripheral blood leukocyte numbers and abdominal cell infiltrates were monitored at 0, 4, 8, and 24 h post-injection. Peripheral blood leukocyte numbers were also determined for 2 h post-injection. For mortality studies, birds were injected intra-abdominally with 1 × 108 CFUs CJ and mortalities were recorded for 72 h post-injection. In the peripheral blood of CJ-injected chicks, total white blood cell (WBC) numbers began increasing by 2 h post-injection, peaking at 4 h post-injection with the predominant cell type being polymorphonuclear leukocytes (heterophils). Total WBCs declined after 8 h and this decline continued at 24 h, with total WBC numbers approaching control values. The injection of CJ into the abdominal cavity caused a rapid rise in abdominal cell infiltrates with the predominant infiltrating leukocytes being heterophils. Peak abdominal heterophil infiltrates were observed at 8 h post-injection, declining only slightly by 24 h post-injection. Mortality in the CJ challenge groups reached 37%. Mortality in the Salmonella enteritidis positive control groups were greater than 50%. The data suggest that Campylobacter infection does stimulate the innate immune response in chickens when administered IA, however, the immune response and infection is not characterized with the high levels of mortality observed with a Salmonella infection. These data provide a basis for a more definitive characterization of chickens' immune response to Campylobacter and a model to evaluate intervention strategies to prevent the infection and colonization of poultry.

Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity.

Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenanceproteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killercells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.

Dynamics of the Indicators of Low Dose Dobutamine Stress-Echocardiography under the Influence of High Doses of Atorvastatin in Patients with ST Elevation Myocardial Infarction

The aim of investigation: to study the effect of early administration high doses of atorvastatin in the acute period of STEMI on the indicators of low dose dobutamine stress-echocardiography and parameters of left ventricular remodeling. Material and Methods: The study included 164 patients with STEMI All patients underwent myocardial revascularization (TLT or PCI) within the first 6 hours. The 1st group included 82 patients who received basic therapy (atorvastatin 20 mg), the 2nd group included 82 patients who took a loading dose of atorvastatin (at a dose of 80 mg per day). Low dose dobutamine stress-echocardiography was performed to detect myocardial stunning after stabilization of the patients condition on 4–6 days of the disease. In addition to general clinical and conventional laboratory research methods, on the 1st day and on the 10th day of treatment, the level of CPK MB, ESR, the number of blood leukocytes, and the level of fibrinogen (FN) were determined. Results: On the 10th day of therapy in patients of both groups, there was a significant increase in ESR (in the 1st group by 2.1 times, in the 2nd - by 1.6 times) and a decrease in the level of CRP (by 3 and 2.65 times, respectively) compared to the first day. The dynamics of these indicators reflects the regular processes of the course of AMI. A more significant change in these parameters was recorded in patients of the 2nd group who took atorvastatin at a dose of 80 mg. At the same time, on the 10th day of AMI, the number of peripheral blood leukocytes significantly decreased in them (p&lt;0.05 when compared between groups). The number of dobutamine-responsive segments (segments with reversible dysfunction) in the group of patients treated with atorvastatin at a dose of 80 mg during myocardial reperfusion was significantly higher than in the control group (p&lt;0.05). Conclusion: It was revealed that conducting of myocardium reperfusion in infarct-related coronary artery with simultaneous use of atorvastatin’s high doses promoted the limitation of myocardial necrosis development, reducing ischemic and reperfusion injuries of myocardium and influenced on the formation of myocardial stunning zones which is a reversible disfunction. The use of atorvastatin in the dose of 80 mg/per day in the first hours after acute myocardial infarction development promotes the improvement of LV systolic indices, prevents the progressing of LV cavity postinfarction dilatation.

High C-Reactive Protein Levels Are Relatedto Better Survival in Patients with Uveal Melanoma.

PurposeTo determine whether peripheral blood leukocyte numbers and serum markers of inflammation can be used to predict which patients with primary uveal melanoma will develop metastasis.DesignRetrospective study.ParticipantsMedical records of patients with uveal melanoma (UM) who received treatment for primary UM between February 1992 and December 2020 at the Erasmus University Medical Center (Rotterdam, The Netherlands) and the Rotterdam Eye Hospital (Rotterdam, The Netherlands) were reviewed.MethodsInclusion criteria were the presence of a melanoma of the choroid or ciliary body and the availability of data from peripheral blood samples taken before treatment of the melanoma. Data including patient demographics, C-reactive protein (CRP) levels; erythrocyte sedimentation rate (ESR); number of leukocytes, neutrophils, monocytes, and lymphocytes; and histopathologic findings were obtained from medical records. Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were calculated.Main Outcome MeasuresMetastasis-free survival.ResultsOf the 807 patients with UM, serum and leukocyte data were available for 183 of them at the time of primary tumor treatment. In the total group, no correlation was found between ESR before treatment; the number of leukocytes; percentages of neutrophils, monocytes, and lymphocytes; or NLR or LMR values and any of the clinical characteristics or metastasis-free survival. Among patients who underwent enucleation, those with negative BAP1 findings showed significantly lower numbers of leukocytes (P < 0.05). In the entire cohort, a significant association was found between high CRP levels and longer metastasis-free survival (MFS; P = 0.049).ConclusionsThe total blood leukocyte number was related to loss of BAP1 staining in patients who underwent enucleation, with lower leukocyte counts correlating with absent BAP1 staining. Higher CRP levels were associated with a longer MFS in the entire cohort. Neither the NLR nor the LMR is a good predictor for metastasis developing in patients with UM.

Two birds with one stone: YQSSF regulates both proliferation and apoptosis of bone marrow cells to relieve chemotherapy-induced myelosuppression

Ethnopharmacological relevanceYiqi Shengsui formula (YQSSF) is a commonly used formula to treat chemotherapy-induced myelosuppression, but little is known about its therapeutic mechanisms. Aim of this studyThis study aims to examine the effect of YQSSF in treating myelosuppression and explore its mechanism. Materials and methodsA myelosuppression BALB/c mouse model was established by intraperitoneal (i.p.) injection of cyclophosphamide (CTX). The efficacy of YQSSF in alleviating chemotherapy-induced myelosuppression was evaluated by blood cell count, immune organ (thymus, spleen, liver) index, bone marrow nucleated cell (BMNC) count and histopathological analysis of bone marrow and spleen. Then, ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to analyze the ingredients of YQSSF extract. Key effects and potential mechanism of YQSSF extract in alleviating myelosuppression were predicted by network pharmacology method. Finally, cell cycle and TUNEL staining of bone marrow cells was detected to verify the key effects, and RT-qPCR or Western blotting were performed to measure the gene and protein expressions of the effect targets respectively to confirm the predicted mechanism of YQSSF for myelosuppression. ResultsYQSSF up-regulated the number of peripheral blood leukocytes and BMNC, reduced spleen index and liver index, improved the pathological morphology of bone marrow and spleen. A total of 40 ingredients were isolated from YQSSF extract using UPLC-Q/TOF-MS analysis. Network pharmacology revealed that YQSSF regulated both proliferation and apoptosis to alleviate myelosuppression. Finally, YQSSF decreased G0/G1 ratio, increased the proportion of bone marrow cells in S phase and proliferation index (PI), and reduced apoptotic cells in femur bone marrow. RT-qPCR and Western blotting showed that YQSSF up-regulated the expression levels of CDK4, CDK6, CyclinB1, c-Myc and Bcl-2, as well as down-regulated the expression levels of Cyt-c, Fas, Caspase-8/3 and p53. ConclusionsYQSSF promotes the proliferation and inhibits the apoptosis of bone marrow cells to relieve chemotherapy-induced myelosuppression.

Ginseng–Astragalus–oxymatrine injection ameliorates cyclophosphamide-induced immunosuppression in mice and enhances the immune activity of RAW264.7 cells

Ethnopharmacological significanceGinseng quinquefolium (L.), Astragalus membranaceus, and Sophora flavescens Aiton are popular folk medicines in many Asian countries and regions. These three traditional Chinese herbs and their extracts have been reported to considerably enhance the immune function. G. quinquefolium (L.) is considered the king of herbs in China. Traditionally, G. quinquefolium (L.) is believed to replenish vitality, which is considered as immune enhancement in modern Chinese pharmacy. One of the main uses of Astragalus is immunity enhancement; S. flavescens and oxymatrine obtained from its extract have been used to treat leukopenia. Considering the pharmacological properties of Ginseng, Astragalus, and oxymatrine, we evaluated the immunopotentiation effects of their combination, Ginseng–Astragalus–oxymatrine (GAO), in the present study. Aim of the studyThis study aimed to expand the clinical application of GAO and to preliminarily explore its mechanism of action by determining whether GAO injection can enhance immunity in vivo and in vitro. MethodsOverall, 17 major chemical components in GAO were analysed using HPLC and LC-MS. The immunity-enhancing effect of GAO was studied in the cyclophosphamide (CTX)-induced immunosuppressive mouse model and RAW 264.7 cells. ResultsQuantitative analysis showed that the potential active components of GAO include at least ginsenosides, astragaloside IV, and oxymatrine. GAO could significantly improve the nonspecific immunity including the indices of the thymus and spleen, number of peripheral blood leukocytes, levels of TNF-α and IL-6, phagocytic function of macrophages, and cytotoxic activity of natural killer (NK) cells. Additionally, GAO enhanced the humoural immunity, characterised by the antibody production ability of B cells, and cellular immunity, characterised by the activity of T cells, in immunosuppressed mouse. Moreover, GAO could enhance the phagocytic and adhesion functions of RAW 264.7 cells, which may be related to the activation of reactive oxygen species and NF-κB signalling pathway. ConclusionGAO could dramatically ameliorate CTX-induced immunosuppression in mouse and stimulate the immune activity in RAW 264.7 cells possibly by activating the NF-κB signalling pathway.

Splenectomy is associated with altered leukocyte kinetics after severe trauma

BackgroundInadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma.MethodsAll adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals.ResultsA total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 h, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions.ConclusionsThis study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.

Iron Oxide Nanoparticles Combined with Cytosine Arabinoside Show Anti-Leukemia Stem Cell Effects on Acute Myeloid Leukemia by Regulating Reactive Oxygen Species.

Background and AimAcute myeloid leukemia (AML), initiated and maintained by leukemia stem cells (LSCs), is often relapsed or refractory to therapy. The present study aimed at assessing the effects of nanozyme-like Fe3O4 nanoparticles (IONPs) combined with cytosine arabinoside (Ara-C) on LSCs in vitro and in vivo.MethodsThe CD34+CD38–LSCs, isolated from human AML cell line KG1a by a magnetic activated cell sorting method, were treated with Ara-C, IONPs, and Ara-C+ IONPs respectively in vitro. The cellular proliferation, apoptosis, reactive oxygen species (ROS), and the related molecular expression levels in LSCs were analyzed using flow cytometry, RT-qPCR, and Western blot. The nonobese diabetic/severe combined immune deficiency mice were transplanted with LSCs or non-LSCs via tail vein, and then the mice were treated with Ara-C, IONPs and IONPs plus Ara-C, respectively. The therapeutic effects on the AML bearing mice were further evaluated.ResultsLSCs indicated stronger cellular proliferation, more clone formation, and more robust resistance to Ara-C than non-LSCs. Compared with LSCs treated with Ara-C alone, LSCs treated with IONPs plus Ara-C showed a significant increase in apoptosis and ROS levels that might be regulated by nanozyme-like IONPs via improving the expression of pro-oxidation molecule gp91-phox but decreasing the expression of antioxidation molecule superoxide dismutase 1. The in vivo results suggested that, compared with the AML bearing mice treated with Ara-C alone, the mice treated with IONPs plus Ara-C markedly reduced the abnormal leukocyte numbers in peripheral blood and bone marrow and significantly extended the survival of AML bearing mice.ConclusionIONPs combined with Ara-C showed the effectiveness on reducing AML burden in the mice engrafted with LSCs and extending mouse survival by increasing LSC’s ROS level to induce LSC apoptosis. Our findings suggest that targeting LSCs could control the AML relapse by using IONPs plus Ara-C.

Corrective effects of original bioflavonoid complex in the cyclophosphamide-induced immunity disorders

Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases.

Hematological indicators of fish of small rivers of the State Nature Reserve «Yaroslavsky»

Data on blood and blood-forming organs of species of the cyprinidae and perch family species living in the rivers of the Yaroslavsky State Nature Reserve were obtained. It was revealed that the hematocrit level in the studied species varied in the range of 23–42 %, the total number of erythrocytes was 1.29–2.20 m / μkl, and the number of leukocytes was 65.9–141.2 thousand/ μkl. The relative number of peripheral blood leukocytes varied in the range: lymphocytes 87–90 %, segmented neutrophils — 3–7.5 %, stab neutrophils — 1–4 %, monocytes and eosinophils — 1–3 %. The relative number of lymphocytes in the organs increased in the series mesonephros, spleen, and liver. The number of hemocytoblasts, on the contrary, decreased. The relative number of myelocytes and metamyelocytes in mesonephros and spleen varied from 1 to 3 %, promyelocytes — from 2 to 4.5 %. Of all the species studied in the liver, myelocytes were found only in the bersh; no hemocytoblasts and promyelocytes were found. Regardless of the organ, the relative number of macrophages, plasmocytes and eosinophils varied from 0 to 3 %, stab neutrophils from 3 to 8.5 %. The number of segmented neutrophils in the mesonephros and spleen varied from 3 to 11 %, in the liver this indicator was 1–3 %. The range of obtained values for the studied indicators was comparable with the previously obtained data for the considered fish species living in relatively clean sections of the Rybinsk Reservoir and its tributaries. It was established that the trophic status of the species exerts the greatest influence on the hematocrit level, the total number of peripheral blood leukocytes, and the relative number of leukocytes in peripheral blood and mesonephros.

Epidemiological and clinical characteristics of COVID-19 patients in Hengyang, Hunan Province, China.

BACKGROUNDIn December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases.AIMTo study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19.METHODSFrom January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software.RESULTSA total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 ± 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 ± 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 ± 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females (P < 0.01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients (P < 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged.CONCLUSIONBased on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.

In Vitro and In Vivo Effects of Holotoxin A1 From the Sea Cucumber Apostichopus japonicus During Ionizing Radiation

Radiation therapy is one of the most important approaches to cancer therapy, but radiotoxicity to normal tissue is a serious limitation of this treatment. Compounds which are able to either sensitize cancer cells or protect normal cells to radiation are of great interest. The cytotoxicity of holotoxin A1 and the effects of radiation against DLD-1 and HT-29 cells were measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. The effect of the combination of holotoxin A1 with X-ray on colony formation of cancer cells was determined by the soft agar assay. The effect of holotoxin A1 on the recovery of peripheral blood leukocyte number, mass, and cellularity of the lymphoid organs of irradiated mice, as well as on growth of murine Ehrlich solid carcinoma was studied. Holotoxin A1 enhanced the sensitivity of colorectal carcinoma cells to radiation in vitro. Injection of holotoxin A1 to mice led to an increase in the spleen endogenous colony number and peripheral blood leukocyte number, as well as the weight and cellularity of the lymphoid organs of the irradiated mice. Holotoxin A1 in combination with X-ray radiation effectively inhibited the growth of Ehrlich solid carcinoma in vivo. Holotoxin A1 is suggested to be a promising agent for improving the efficiency of radiotherapy.

UPLC-MS-based serum metabolomics reveals protective effect of Ganoderma lucidum polysaccharide on ionizing radiation injury

Ethnopharmacological relevanceGanoderma lucidum Polysaccharide (GLP),traditional Chinese medicine (TCM) active ingredient, has a long history and has good curative effects on radiation injury. However, the mechanism of GLP treating radiation injury has not been clearly elucidated. The aim of the studyThis study was aimed to investigate the preventive effects of GLP on mice with radiation injury and to explore its mechanisms by serum metabolomics. Materials and methodsThirty mice were randomly divided into three groups,and namely 10 per group. The normal control group and the radiation model with normal saline and GLP group with GLP treatment (96 mg·kg-1) for 14 days. 2 h after 7th day after the intragastric administration, the model group and GLP group were subjected to whole body irradiation by X-rays except the normal control group. The peripheral blood WBC, RBC, HGB, PLT indicators.UPLC-Q-TOF-MS technique was used to analyze the serum of normal group, model group and GLP group, and to explore its potential key biomarkers and corresponding related metabolic pathways. ResultsThe number of peripheral blood leukocytes (WBC) in the radiation model group was lower than that in the GLP group and the number of platelets (PLT) in the GLP group was significantly higher than that in the model group.Combined with the methods of principal component analysis (PCA), projection to latent structure-discrimination analysis (PLS-DA), three group were clearly distinguished from each other and 18 metabolites were identified as the potential biomarkers in the GLP treated mice. The identified biomarkers indicated that there were perturbations of the taurine and hypotaurine metabolism and glycerophospholipid metabolism. ConclusionGLP can play a role in radiation protection by improving the expression of related potential biomarkers and related metabolic pathways in serum of radiation-induced mice.

Diagnostic Value of miR-34a in Bone Marrow Mononuclear Cells of Acute Myeloid Leukemia Patients.

The current study aims to analyze the expression of miR-34a in bone marrow mononuclear cells (BMMCs) of acute myeloid leukemia (AML) patients and its possible role in the development of leukemia. Real-time fluorescent quantitative PCR was used to detect the expression of miR-34a in bone marrow of 40 patients with initial treatment of AML, 22 patients with complete remission AML, 13 patients with refractory recurrence, 20 patients with non-hematological tumors and healthy persons. Pearson's correlation was performed to analyze the correlation between the expression level of miR-34a and clinical indicators in patients. The expression of miR-34a in the initial treatment group, complete remission group and refractory relapse group of AML patients was higher than that in the control group. In addition, the expression of miR-34a in the complete remission group was higher than that in the initial treatment group. Moreover, the expression of miR-34a in the refractory relapse group was lower than that in the initial treatment group. The expression level of miR-34a in initial treatment AML group was negatively correlated with the number of bone marrow primary immature cells, but not with the number of peripheral blood leukocytes, platelet count, hemoglobin content, age, gender, and chromosomal abnormalities. The expression of miR-34a in bone marrow mononuclear cells of patients with AML was down-regulated and related to tumor load. It may play an important role in the occurrence and development of leukemia and may become a new molecular marker for the diagnosis of AML.

Effects of Indralin on Immunohematological Parameters and DNA Damage in Irradiated ICR (CD-1) Outbred Mice

Abstract—Intragastric administration of radioprotector indralin (B-190 drug) to outbred SPF ICR (CD-1) mice 15 minutes before X-ray irradiation at doses of 6 Gy (LD-10/30), 6.5 Gy, and 7 Gy (LD-100/30) increases the 30-day survival of the animals and positively affects the state of the central organs of immunity and hematopoiesis, as well as the number of peripheral blood leukocytes. In addition, a positive effect on the behavioral reactions of the irradiated animals and striated muscles strength was noted. In addition to these secondary features of the indralin positive effect, a significant reduction of radiation-induced DNA damage in spleenocytes was observed using flow cytometry analysis of phosphorylated histone Н2АХ (γН2АХ) (1 h and eight days after X-ray irradiation) and DNA-comet assay (eight days after X-ray irradiation). The abovementioned methods are recommended for experiments investigating the influence of radioprotective drugs on DNA damage induction and repair in the irradiated organism, as well as for initial searching of potential radioprotectors and assessment of their effectiveness level in clinical practice and experiments.

Predictors of non-cystic fibrosis bronchiectasis in Indigenous adult residents of central Australia: results of a case-control study.

The human T-cell leukaemia virus type 1 (HTLV-1) is associated with pulmonary inflammation. Indigenous Australians in central Australia have a very high prevalence of HTLV-1 infection and we hypothesised that this might contribute to high rates of bronchiectasis in this population.80 Indigenous adults with confirmed bronchiectasis, each matched by age, sex and language to two controls without bronchiectasis, were recruited. Case notes and chest imaging were reviewed, HTLV-1 serology and the number of peripheral blood leukocytes (PBLs) infected with HTLV-1 (pro-viral load (PVL)) were determined, and radiological abnormality scores were calculated. Participants were followed for a mean±sd of 1.14±0.86 years and causes of death were determined.Median (interquartile range) HTLV-1 PVL for cases was 8-fold higher than controls (cases 213.8 (19.7–3776.3) copies per 105 PBLs versus controls 26.6 (0.9–361) copies per 105 PBLs; p=0.002). Radiological abnormality scores were higher for cases with HTLV-1 PVL ≥1000 copies per 105 PBLs and no cause of bronchiectasis other than HTLV-1 infection. Major predictors of bronchiectasis were prior severe lower respiratory tract infection (adjusted OR (aOR) 17.83, 95% CI 4.51–70.49; p<0.001) and an HTLV-1 PVL ≥1000 copies per 105 PBLs (aOR 12.41, 95% CI 3.84–40.15; p<0.001). Bronchiectasis (aOR 4.27, 95% CI 2.04–8.94; p<0.001) and HTLV-1 PVL ≥1000 copies per 105 PBLs (aOR 3.69, 95% CI 1.11–12.27; p=0.033) predicted death.High HTLV-1 PVLs are associated with bronchiectasis and with more extensive radiological abnormalities, which may result from HTLV-1-mediated airway inflammation.