Blood Cells Research Articles

Recent efficacy and long-term survival of Astragalus polysaccharide combined with gemcitabine and S-1 in pancreatic cancer

BACKGROUND Pancreatic cancer is a highly malignant tumor with a rapid progression rate and a high susceptibility to infiltration and metastasis. Astragalus polysaccharide (APS), a pure Chinese medicine preparation primarily made from the traditional Chinese herb Astragalus , plays a positive role in the treatment of many malignant tumors. AIM To explore the recent efficacy of APS combined with gemcitabine plus tegafur gimeracil oteracil potassium capsule (S-1) (GS) regimen in the treatment of pancreatic cancer and assess its effect on the immune function and long-term survival of patients. METHODS A total of 97 patients who were diagnosed with pancreatic cancer and received GS chemotherapy at The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) from March 2021 to December 2021 were included in the retrospective analysis. Among them, 41 patients received APS combined with GS chemotherapy, and 56 patients received GS chemotherapy only. The recent efficacy, immune function, adverse reactions, and long-term survival were compared among these patients. RESULTS After 4 cycles of treatment, the objective response rate of patients receiving the combined therapy of APS and GS was 51.22%, and the disease control rate (DCR) was 56.10%, higher than those of patients receiving the monotherapy with GS alone (30.36% and 35.71%, respectively). Besides, the percentages of CD3+ T cells (50.18% ± 9.57%) and CD4+ T cells (31.52% ± 5.33%) in the peripheral blood of patients receiving the combined therapy of APS and GS were higher compared with those treated with GS regimen alone [(44.06% ± 8.55%) and (26.01% ± 7.83%), respectively]. Additionally, the incidences of leukopenia, thrombocytopenia, and fatigue in patients receiving the combined therapy of APS and GS were significantly lower than those in patients receiving the monotherapy of GS alone (17.07%, 9.76%, 31.71% vs 37.50%, 28.57%, 60.71%). Moreover, the median survival time of patients receiving the combined therapy of APS and GS was 394 days, significantly longer than that of patients receiving the monotherapy of GS alone (339 days) (hazard ratio (HR): 0.66; 95%CI: 0.45-0.99; P = 0.036). All these differences were statistically significant (P < 0.05). CONCLUSION The combined therapy of APS and GS improved the recent efficacy and long-term survival of patients with pancreatic cancer and alleviated chemotherapy-induced immune suppression and adverse reactions.

Diagnosis and typing of leukemia using a single peripheral blood cell through deep learning

AbstractLeukemia is highly heterogeneous, meaning that different types of leukemia require different treatments and have different prognoses. Current clinical diagnostic and typing tests are complex and time‐consuming. In particular, all of these tests rely on bone marrow aspiration, which is invasive and leads to poor patient compliance, exacerbating treatment delays. Morphological analysis of peripheral blood cells (PBC) is still primarily used to distinguish between benign and malignant hematologic disorders, but it remains a challenge to diagnose and type these diseases solely by direct observation of peripheral blood(PB) smears by human experts. In this study, we apply a segmentation‐based enhanced residual network that uses progressive multigranularity training with jigsaw patches. It is trained on a self‐built annotated dataset of 21,208 images from 237 patients, including five types of benign white blood cells(WBCs) and eight types of leukemic cells. The network is not only able to discriminate between benign and malignant cells, but also to typify leukemia using a single peripheral blood cell. The network effectively differentiated acute promyelocytic leukemia (APL) from other types of acute myeloid leukemia (non‐APL), achieving a precision rate of 89.34%, a recall rate of 97.37%, and an F1 score of 93.18% for APL. In contrast, for non‐APL cases, the model achieved a precision rate of 92.86%, but a recall rate of 74.63% and an F1 score of 82.75%. In addition, the model discriminates acute lymphoblastic leukemia(ALL) with the Ph chromosome from those without. This approach could improve patient compliance and enable faster and more accurate typing of leukemias for early diagnosis and treatment to improve survival.

Diagnosis and Treatment of Polycythemia Vera

ImportancePolycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis, affects approximately 65 000 people in the US, with an annual incidence of 0.5 to 4.0 cases per 100 000 persons.ObservationsErythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion, although thrombocytosis (53%) and leukocytosis (49%) are common. Patients may have pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%), and splenomegaly (36%) with abdominal discomfort. More than 95% of patients have a JAK2 gene variant, which helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea. Among 7 cohorts (1545 individuals), the median survival from diagnosis was 14.1 to 27.6 years. Prior to or at the time of PV diagnosis, arterial thrombosis occurred in 16% of patients and 7% had venous thrombotic events, which could involve unusual sites, such as splanchnic veins. PV is also associated with an increased bleeding risk, especially in patients with acquired von Willebrand disease, which can occur with extreme thrombocytosis (platelet count, ≥1000 × 109/L). All patients with PV should receive therapeutic phlebotomy (goal hematocrit, <45%) and low-dose aspirin (if no contraindications). Patients who are at higher risk of thrombosis include those aged 60 years or older or with a prior thrombosis. These patients and those with persistent PV symptoms may benefit from cytoreductive therapy with hydroxyurea or interferon to lower thrombosis risk and decrease symptoms. Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. About 12.7% of patients with PV develop myelofibrosis and 6.8% develop acute myeloid leukemia.Conclusions and RelevancePV is a myeloproliferative neoplasm characterized by erythrocytosis and is almost universally associated with a JAK2 gene variant. PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis.

Abstract IA016: Vascular control of metastasis

Abstract The molecular analysis of tumor vessel interactions during tumor progression and metastasis has primarily focused on the study of tumor cell-derived angiogenic and lymphangiogenic signals with the purpose to exploit such factors as therapeutic targets. Angiogenic factors activate endothelial cells in nearby blood and lymphatic capillaries to sprout towards the tumor. Tumor angiogenesis thereby not only nourishes the growing tumor, but access to the blood and lymphatic vasculatures enables cells from the primary tumor to enter the circulation to eventually form metastases at distant sites. The complex cellular interactions between tumor cells and endothelial cells have in this context mostly been studied from a tumor cell-centric perspective, i.e., the tumor cells send signals to which endothelial cells merely respond. Yet, the past decade has witnessed a fundamental change of paradigm with the discovery that the vascular endothelium does not just respond to exogenous cytokines but exerts active ’angiocrine’ gatekeeper roles controlling their microenvironment in an instructive manner. We have applied the concepts of angiocrine signaling towards the study of tumor progression and metastasis. Employing novel surgical preclinical metastasis models that better mimic tumor progression and the response to therapy as it occurs in humans, we have molecularly dissected vascular endothelial cells in progressing primary tumors as well as in the pre-metastatic and metastatic niches. These experiments were on the one hand aimed at establishing the systems map of endothelial transcriptomic changes during tumor progression and metastasis and on the other hand to identify and validate novel therapeutic targets. This presentation will review recent advances in the field of tumor microenvironment research and present novel angiocrine signaling mechanisms as promising targets of future mechanism-driven anti-metastatic therapy. Citation Format: Hellmut G. Augustin. Vascular control of metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA016.

Abstract B034: Engineering the tumor microenvironment: Patient-specific microphysiological systems of the head and neck cancer tumor microenvironment

Abstract Introduction: Survival rates in advanced head and neck cancer (HNC) remain poor with no clinically approved biomarkers to predict treatment efficacy. HNC is a highly heterogenous disease and the lack of available models that capture patient heterogeneity and the complexity of the tumor microenvironment (TME) contributes to these poor patient outcomes. Microphysiological systems (MPS) are complex multicellular in vitro models that can recapitulate three-dimensional organ structure and function. The low cell number requirements for MPS permits the creation of patient-specific TME models, where all the cell types can be isolated from a single piece of tumor tissue. These patient-specific MPS represent a promising strategy for elucidating the contribution of the TME to treatment resistance, predicting the best treatment for each patient and improving patient outcomes in HNC. Here, we report a patient-specific MPS that contains multiple TME compartments and recapitulates patient heterogeneity. Methods: Tumor tissue was collected from patients with oral cavity carcinoma undergoing standard of care surgery followed by radiation or chemoradiation. Tissue from each patient was digested and tumor infiltrating leukocytes (TIL) were isolated using CD45 magnetic beads, while epithelial cells and fibroblasts were expanded in culture using specific media formulations. Tissue was also snap frozen for single cell RNA sequencing analysis. To build the MPS, a custom designed microfluidic device was filled with a hydrogel matrix containing patient-matched TIL, fibroblasts and epithelial spheroids to mimic the solid tumor. Lumens molded from the hydrogel were seeded with blood or lymphatic endothelial cells to create vasculature. Multiple replicate MPS can be built from each patient, which are cultured in an optimized media formulation to support the multiple primary cell types. Patient-specific MPS were treated with radiation or cisplatin + radiation to mimic the treatment the patient received. Multiple orthogonal endpoints were measured including tumor cell migration and viability, cytokine secretion and angiogenesis. Single cell sequencing was also performed on the original tumor tissue and matched MPS. Results: We have successfully created patient-specific models of the HNC TME. Single cell RNA sequencing analysis of the MPS suggests that cellular heterogeneity is being retained. Patient characteristics varied between MPS with some patient TME MPS showing highly migratory tumor cells or angiogenic responses. Treatment responses were measured for each patient-specific MPS and ongoing work will characterize the contributions of the TME to treatment resistance. These data demonstrate the feasibility of using patient-specific MPS to investigate the contribution of the TME to treatment response and resistance and lays important groundwork for using MPS to identify patient treatment responses. Citation Format: Adeel Ahmed, Marcos Lares, Fauzan Ahmed, Adam R. Burr, Paul M. Harari, David J. Beebe, Sheena C. Kerr. Engineering the tumor microenvironment: Patient-specific microphysiological systems of the head and neck cancer tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B034.

Evaluation of Different Swab Wetting Chemicals Affecting the Yield of DNA Obtained From Biological Evidence on Cartridge Casings

Cartridge casings made from transition metals can be examined ballistically and also serve as significant evidence by containing touch DNA. However, the success rate of profiles obtained from this type of evidence is generally low. To enhance the success of DNA profiling from suspects' biological evidence, using swabs moistened with chemicals can be beneficial. Swabs are typically moistened with water, whose hypotonic nature disrupts cell integrity, causing the release of DNA. However, water is not the only agent used for moistening swabs; various buffer solutions are also utilized. The ability of swabs to transfer touch DNA depends on the type of buffer solution used. Sodium dodecyl sulfate (SDS), a strong anionic detergent, denatures non-covalently linked secondary and tertiary structures to increase the release of bound DNA. Another buffer solution used for swab moistening is Te+4 buffer, which contains EDTA and Tris. EDTA chelates metal ions, inactivating enzymes that could potentially damage DNA, while Tris adjusts the pH to an optimal level. This study aims to compare the effectiveness of microfibre and cotton swabs moistened with SDS, Te+4 buffer, and water in recovering genetic material from blood and epithelial cells deposited on brass cartridge casings. The study also evaluates the impact of firing on the quality of DNA profiles. Among the profiles obtained, the swabs moistened with SDS produced the highest rate of complete profiles at 44%, while the lowest rate of complete profiles at 22% was observed with swabs moistened with Te+4 buffer. SDS is particularly advantageous over water when used on casings with epithelial cells. Microfibre swabs are more effective in eliminating degradative factors caused by firing, thus enhancing profiling success. Comparisons of the RFU values indicate that casings yield lower values compared to cartridges, supporting the negative impact of the high heat, pressure, and residues generated during firearm discharge.

Biofabricated zinc oxide nanoparticles mitigate acrylamide-induced immune toxicity and modulate immune-related genes and microRNA in rats.

This study evaluated the potential efficacy of eco-friendly biofabricated zinc oxide nanoparticles (GS-ZnONP) (10mg/kg b.wt) to reduce the impacts of long-term oral acrylamide (ALD) exposure (20mg/kg b.wt) on the blood cells, immune components, splenic oxidative status, and expression of CD20, CD3, CD4, CD8, TNF-α, caspase-3, microRNA-181a-5p, and microRNA-125-5p in rats in a 60-day experiment. The study findings revealed that GS-ZnONP significantly corrected the ALD-induced hematological alterations. Additionally, the ALD-induced increase in the serum C3, splenic ROS, CD4, CD8, and MDA and histological alterations were significantly repressed in the ALD + GS-ZnONP-treated rats. Instead, the depleted splenic antioxidants and Zn contents were markedly reestablished in the ALD + GS-ZnONP-treated group. Additionally, a significant upregulation of expression of splenic CD3, CD4, CD8,CD20, TNF-α, and caspase-3, but downregulation of microRNA-181a-5p and microRNA-125-5p was detected in the ALD-exposed group. Yet, the former deviations in the gene expressions were corrected in the ALD + GS-ZnONP-treated rats. Furthermore, GS-ZnONP treatment significantly minimized the increased caspase-3 and TNF-α immunoexpression in the splenic tissues of ALD-exposed rats. Conclusively, the study findings proved the efficacy of GS-ZnONP in rescuing ALD-induced disturbances in blood cell populations, immune function, splenic antioxidant status, and immune-related gene expression.

Multi-omics investigation into long-distance road transportation effects on respiratory health and immunometabolic responses in calves.

Long-distance road transportation is a common practice in the beef industry, frequently resulting in bovine respiratory disease (BRD) and compromised growth performance. However, a comprehensive investigation integrating clinical performance, physiological conditions, and nasopharyngeal microflora remains lacking. This study aimed to evaluate the respiratory health and immunometabolic status of 54 beef calves subjected to a 3000-km journey. The respiratory health of calves was monitored over 60 days post-arrival using a modified clinical scoring system. Nasopharyngeal microflora and venous blood samples were collected at 3 time points: before transportation (A), 30 days post-arrival (B), and 60 days post-arrival (C), for 16S rRNA microbiomics, whole-blood transcriptomics, serum metabolomics, and laboratory assays. Within the first week post-arrival, the appetite and mental scores of calves dropped to zero, while other respiratory-related scores progressively declined over the 60 days. The α-diversity of nasopharyngeal microflora in calves was similar at time points A and B, both significantly higher than at time point C. The structure of these microbial communities varied significantly across different time points, with a notably higher relative abundance of BRD-related genera, such as Pasteurella and Mannheimia, detected at time point A compared to B and C. The composition and gene expression profiles of circulating blood cells at time point A were significantly different from those at B and C. Specifically, higher expression levels of oxidative- and inflammatory-related genes, cytokines, and enzymes were observed at time point A compared to B and C. Higher levels of catabolism-related metabolites and enzymes were detected at time point A, while higher levels of anabolism-related metabolites and enzymes were observed at time points B and C. Additionally, significant correlations were found among microorganisms, genes, and metabolites with differing abundances, expression levels, and concentrations across time points. Stronger correlations were observed between calves' performance and nasopharyngeal microflora and immunometabolic status at time point A compared to B or C. Collectively, these results confirm that 3000 km of road transportation significantly alters the composition and gene expression profiles of circulating white blood cells in calves, affects their metabolic processes, disrupts the balance of the respiratory microbial community, and leads to pronounced respiratory symptoms that persist for at least 60 days. During this period, the influenced composition and gene expression of circulating blood cells, metabolic processes, and nasopharyngeal microbial community gradually return to equilibrium, and the respiratory symptoms gradually diminish. This observational research indicates that transportation induces BRD in calves by disrupting the homeostasis of their immune function, metabolic processes, and nasopharyngeal microbial community. However, these results and their underlying molecular mechanisms warrant further validation through well-designed in vivo and in vitro confirmatory experiments with larger sample size. Video Abstract.

Association between anaemia and aflatoxin B1 and fumonisin B1 exposure in HIV-infected and HIV-uninfected pregnant women from Harare, Zimbabwe.

Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are poisons that contaminate poorly stored staple foods in resource-limited settings. Antenatal AFB1 and FB1 exposure may cause anaemia. We aimed to determine the associations of urinary aflatoxin M1 (AFM1) and FB1, biomarkers of AFB1 and FB1 exposure, respectively, with erythrocyte parameters and anaemia. A retrospective cross-sectional study was conducted in 68 HIV-infected and 61 HIV-uninfected pregnant women ≥ 20 weeks gestational age in Harare, Zimbabwe. AFM1 and FB1 were measured in urine via competitive ELISA, and levels were grouped into tertiles. The erythrocyte parameters assessed were haemoglobin (Hb), mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell (RBC), haematocrit (HCT), and red blood cell distribution width. Associations of urinary AFM1 and FB1 with erythrocyte parameters, and anaemia were assessed in a multiple regression controlled for potential confounders. The presence of FB1 in urine decreased Hb levels in all women (β= -0.98, 95% CI: -1.94, 0.02) and HIV-uninfected (β= -1.99, 95% CI: -3.71, -0.26). FB1 tertile 3 decreased Hb levels (β= -0.88, 95% CI: -1.74, 0.01) and HCT levels (β= -2.65, 95% CI: -5.26, 0.03) in HIV-infected. AFM1 tertile 2 decreased RBC levels in HIV-infected (β= -0.34, 95% CI: -0.71, -0.03). The presence of FB1 in urine increased anaemia risk in HIV-uninfected (OR: 10.68 95% CI: 1.02, 112.34). AFM1 tertile 2 increased macrocytic anaemia risk in HIV-infected (OR: 13.72, 95% CI: 0.92, 203.55). There is need to ensure food safety through monitoring and nutritional interventions to improve maternal-infant health outcomes.

Resolvin E1 and Inhibition of BLT2 Signaling Attenuate the Inflammatory Response and Improve One-Lung Ventilation-Induced Lung Injury

ABSTRACT Introduction One-lung ventilation (OLV) is a prevalently used technique to sustain intraoperative pulmonary function. Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator, accelerates the resolution of inflammation in the lungs. However, its therapeutic effects on OLV-induced lung injury remain unclear. Methods We initially developed an OLV rat model and treated it with RvE1. Subsequently, we assessed the wet/dry ratio of the lung tissue, performed hematoxylin and eosin staining, and calculated the ratio of polymorphonuclear cells to white blood cells in the bronchoalveolar lavage fluid. Additionally, we assessed apoptosis, inflammatory factor levels, and lung permeability in the rat lung tissues in the RvE1 treated and untreated groups and explored the molecular mechanisms mediated by RvE1. Results Our results indicated that RvE1 alleviated lung injury and inflammation and improved lung tissue apoptosis and permeability in OLV rats. Moreover, RvE1 suppressed the expression of the BLT1/2 signaling pathway and its ligands. The use of BLT2 and BLT1 inhibitors (LY255283 and U-75302, respectively) enhanced RvE1’s anti-inflammatory effects and reduced lung injury. Furthermore, synergistic treatment with the BLT2 inhibitor and RvE1 provided grater benefits by more effectively inhibiting the NF-kB, p38 MAPK, and ERK pathways. Discussion RvE1 and the inhibition of BLT2 signalling reduce the inflammatory response and mitigate OLV-induced lung injury. These findings suggest a novel therapeutic pathway for managing OLV-related complications.

Intraventricular antibiotics for severe central nervous system infections: a case series.

Severe central nervous system infections (CNSI), including community-acquired CNSI (CA-CNSI) and healthcare-associated ventriculitis and meningitis (HAVM), present high morbidity and mortality. Intraventricular antibiotic treatment (IVT) is advisable for these infections, though evidence is limited. We retrospectively analyzed data on 27 patients who received IVT for severe CA-CNSI and HAVM over 10 years, assessing clinical and paraclinical features, such as baseline severity and functional outcome, antibiotics, microbiological and laboratory data. Comparisons were made between patients affected by CNSI and HAVM and those with favorable and unfavorable outcomes, based on the modified Rankin scale.Gram-positive organisms dominated in CA-CNSI (64%), while gram-negative organisms were more frequent in HAVM (64%). Patients received a median of 30 days of intravenous antibiotics and 11 days of IVT, with no significant difference between CA-CNSI and HAVM. IVT-associated toxicity was rare. Patients with favorable outcomes (64%) had higher initial cerebrospinal fluid- white blood cell count (CSF-WBC), that decreased more rapidly than in patients with unfavorable outcomes. CSF-WBC dynamics did not differ between CA-CNSI and HAVM patients.Rapid decline in CSF-WBC after initiation of IVT was associated with favorable outcome. Despite severe neurological impairment at admission, most survivors achieved favorable long-term outcomes.

Toxic effects of chlorpyrifos on biochemical composition, enzyme activity and gill surface ultrastructure of three species of small fishes from India.

The effects of chlorpyrifos, a frequently detected organophosphate in aquatic ecosystems, on biochemical (protein and glycogen) contents and oxidative enzyme activities (catalase and lipid peroxidation) in liver, muscle and gill tissues of three freshwater fish Trichogaster fasciata, Mystus vittatus and Heteropneustes fossilis were evaluated after 21-day exposure to 1 and 10% of 96h LC50 of this pesticide, which were 1.63 and 16.3µg L-1; 5.87 and 58.7µg L-1 and 2.12 and 21.2µg L-1, respectively. On comparing with control, significant reductions in protein concentration were found in liver, muscle and gill of the three fishes treated with both higher as well as lower concentrations of the pesticide except in gill of M. vittatus and liver of H. fossilis treated with the lower concentrations. Glycogen content reductions were significant in the liver and muscle of the fishes, as well as gill tissue of T. fasciata treated with the two pesticide concentrations. Significant elevations of catalase activity were found in liver of the three fishes treated with the higher concentrations, in muscle tissues of both T. fasciata and M. vittatus treated with both the concentrations and in gills of the three fishes except H. fossilis treated with the lower concentration of the pesticide. Significant elevations of lipid peroxidation level were also found in liver of all the three fish species treated with the higher concentrations, in the muscle tissue of M. vittatus as well as in the gill of T. fasciata and H. fossilis treated with both the concentrations of the pesticide. Chlorpyrifos exposed gill ultrastructure of T. fasciata, M. vittatus and H. fossilis revealed concentration-dependent effects of the pesticide on gill surface ultrastructure which include distortion of primary and secondary lamellae, deterioration of pavement cell and microridge structures, extrusion of red blood cells (RBCs), secretion of mucous layer on filament, sloughing of primary lamellae and clumping of secondary lamellae. The present study parameters could serve as useful biomarkers for evaluating the risk of pesticide toxicity to fish. These findings also point out the possible health risks to the consumers of these fish captured from contaminated water bodies.

Development and validation of a predictive risk tool for VTE in women with breast cancer under chemotherapy: a cohort study in China.

The incidence of venous thromboembolism (VTE) is significantly elevated in breast cancer patients, with a three-to-fourfold increase, and further escalates to sixfold in those undergoing chemotherapy. This study aims to identify the risk factors for VTE and develop a Nomogram risk prediction model distinct from the traditional Khorana score. Univariate Cox regression analysis assessed the impact of each variable on the occurrence of VTE, while stepwise multivariate Cox regression analysis identified independent predictors. Based on these results, we constructed a Nomogram model. The model's performance was validated using the C-index, receiver-operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). Comparisons were made with the Khorana score to evaluate the practical application value. Out of the 903 patients, 108 (11.96%) developed VTE. Cox regression analysis identified that Stage, undergoing surgery, age, white blood cells (WBC), D-dimer, and carcinoembryonic antigen (CEA) were significant risk factors for VTE (P < 0.05). The Nomogram model's C-index was 0.77 (95% CI 0.72-0.83) in the training set and 0.76 (95% CI 0.69-0.84) in the validation set. The model demonstrated excellent predictive accuracy and generalizability on the receiver-operating characteristic (ROC) curves and calibration curves. Compared to the traditional Khorana score, the Nomogram model showed superior predictive accuracy and greater clinical benefit. This study established a VTE risk prediction model for breast cancer patients undergoing chemotherapy. The model is characterized by its intuitive and straightforward application, making it highly suitable for rapid VTE risk assessment in clinical practice.

A higher JAK2V617F allele burden may be a risk factor for hemorrhagic events in younger patients with polycythemia vera

ABSTRACT Objectives: Hemorrhagic events are a rare but potentially fatal complication in patients with polycythemia vera (PV). Methods: We analyzed the characteristics of hemorrhagic events in 267 patients with PV. Results: A median follow-up of 4.8 years revealed that 23 (8.6%) hemorrhagic events occurred. Significantly more hemorrhagic events occurred in younger patients aged below 60 years (n = 72) than in older patients aged 60 years or above (n = 191) (n = 12 [16.7%] vs. n = 11 [5.8%], respectively, P = 0.012). In univariate analysis among the younger patients, white blood cell (WBC) count ≥ 15 × 109/L (hazard ratio [HR] = 7.746, 95% confidence interval [CI] 2.082-28.830, P = 0.002), palpable splenomegaly (HR = 5.629, 95% CI 1.193–26.550, P = 0.029), and JAK2V617F allele burden ≥ 80% (HR = 22.850, 95% CI 2.885–181.00, P = 0.003) were associated with an increased risk of hemorrhagic events. In multivariate analysis, JAK2V617F allele burden ≥ 80% (HR = 9.394, 95% CI 1.046–84.380, P = 0.046) was a significant risk factor. Conclusions: There is an increased risk of hemorrhagic events after diagnosis in younger PV patients with a high JAK2V617F allele burden, high WBC count or palpable splenomegaly. It is important to consider treatment options that aim to avoid hemorrhagic events by reducing the JAK2V617F allele burden in younger PV patients.

MEGALOBLASTIC CRISIS IN SICKLE CELL DISEASE–A RARE PHENOMENA WITH AVAILABLE REVIEW OF LITERATURE

Sickle cell disease (SCD) is an inherited disease where some red blood cells are shaped like sickles or crescent moons. This condition affects the blood and various organs of the body. These sickle cells also become rigid and sticky, which can slow or block blood flow, resulting in episodes of sickness that produce pain and other crisis. There are different types of crisis. SCD with a megaloblastic crisis is rare. The frequency of the carrier state determines the prevalence of sickle cell anemia. Here we describe a 20 y old female patient with sickle cell disease who experienced a megaloblastic crisis.

Nettle (Urtica dioica) supplementation: impact on growth, hematology, immune response, and resilience to Aeromonas hydrophila in Labeo rohita fingerlings.

The significance of plant-derived products in aquaculture lies in their potential to offer sustainable alternatives, promoting eco-friendly practices. This study investigated the impact of nettle (Urtica dioica) leaves powder on the growth efficiency, hemato-biochemical variables and non-specific immune system of rohu, Labeo rohita fingerlings. To achieve this objective, sample average weight (5.23 ± 0.34g) were categorized into four groups, namely control, T1, T2 and T3 in triplicate and administered diets fortified with nettle in amounts of 0, 1, 3 and 5% respectively for a duration of 60 days. After 60 days of fortified diet, the fish underwent intraperitoneal injection with bacteria (Aeromonas hydrophila), and subsequent relative percentage survival (RPS) was observed. The growth performance, including "weight gain (WG), specific growth rate (SGR), feed conversion ratio (FCR) and feed efficiency ratio (FER)", were notably higher in the T3 group (5%) than in others. The hematological values of White blood cell, hematocrit, and hemoglobin revealed higher levels with a fortified diet. The dietary supplementation of nettle reduced serum cholesterol and glucose concentration, whereas it increased albumin, globulin, and total protein in the fish blood. Enhancements in lysozyme and myeloperoxidase activity were observed in the intervention groups with feed containing nettle supplementation. The nettle diet at a 5% concentration demonstrated a higher RPS than the others following injection with A. hydrophila. The findings indicate the potential of nettle as a valuable nutritional supplement for increasing fish immunological reaction and bolstering pathogen resistance.

Identifying slow-growing commercial pigs using growth performance and health indicators.

This study aimed to evaluate the growth performance and health status of commercial pigs in different body weight (BW) groups and develop methods for identifying slow-growing pigs. The research observed 79 commercial pigs grouped from 104 to 202 days of age, collecting data on BW, feed intake, and body condition score (BCS) from caliper. Results showed that BCS were highly correlated with BW (r > 0.85, P < 0.001), providing a simple method for assessing commercial pig BW. Commercial pigs with slaughter BWs below 114kg at approximately 200 days old were identified as slow-growing individuals. White blood cell count, insulin-like growth factor binding protein-3, and blood urea nitrogen were identified as potential biomarkers for identifying slow-growing pigs. Economic analysis revealed that profitability across all BW groups was highly sensitive to market conditions, with feed costs being the most significant factor. Low BW groups performed better in low-price markets but reach break-even points later under medium to high-price scenarios.

Sirtuin inhibitors reduce intracellular growth of M. tuberculosis in human macrophages via modulation of host cell immunity.

Host-directed therapies aiming to strengthen the body's immune system, represent an underexplored opportunity to improve treatment of tuberculosis (TB). We have previously shown in Mycobacterium tuberculosis (Mtb)-infection models and clinical trials that treatment with the histone deacetylase (HDAC) inhibitor, phenylbutyrate (PBA), can restore Mtb-induced impairment of antimicrobial responses and improve clinical outcomes in pulmonary TB. In this study, we evaluated the efficacy of different groups of HDAC inhibitors to reduce Mtb growth in human immune cells. A panel of 21 selected HDAC inhibitors with different specificities that are known to modulate infection or inflammation was tested using high-content live-cell imaging and analysis. Monocyte-derived macrophages or bulk peripheral blood cells (PBMCs) were infected with the green fluorescent protein (GFP)-expressing Mtb strains H37Ra or H37Rv and treated with HDAC inhibitors in the micromolar range in parallel with a combination of the first-line antibiotics, rifampicin, and isoniazid. Host cell viability in HDAC inhibitor treated cell cultures was monitored with Cytotox-red. Seven HDAC inhibitors were identified that reduced Mtb growth in macrophages > 45-75% compared to average 40% for PBA. The most effective compounds were inhibitors of the class III HDAC proteins, the sirtuins. While these compounds may exhibit their effects by improving macrophage function, one of the sirtuin inhibitors, tenovin, was also highly effective in extracellular killing of Mtb bacilli. Antimicrobial synergy testing using checkerboard assays revealed additive effects between selected sirtuin inhibitors and subinhibitory concentrations of rifampicin or isoniazid. A customized macrophage RNA array including 23 genes associated with cytokines, chemokines and inflammation, suggested that Mtb-infected macrophages are differentially modulated by the sirtuin inhibitors as compared to PBA. Altogether, these results demonstrated that sirtuin inhibitors may be further explored as promising host-directed compounds to support immune functions and reduce intracellular growth of Mtb in human cells.

Progress in application of medical absorbable haemostatic materials for haemostasis in orthopaedic surgery

The application progress of medical absorbable haemostatic material (MAHM) in hemostasis during orthoapedic surgery was reviewed, in order to provide reference for clinical hemostasis program. The domestic and foreign literature on the application of MAHM for hemostasis in orthopedic surgery was extensively reviewed and summarized. According to biocompatibility, MAHM can be divided into oxidized cellulose/oxidized regenerated cellulose materials, chitosan and its derivatives materials, starch materials, collagen and gelatin materials, and fibrin glue materials, etc., which can effectively reduce blood loss when used in orthopedic surgery for hemostasis. Each hemostatic material has different coagulation mechanism and suitable population. Oxidized cellulose/oxidized regenerated cellulose, chitosan and its derivatives, starch hemostatic material mainly stops bleeding by stimulating blood vessel contraction and gathering blood cells, which is suitable for people with abnormal coagulation function. Collagen, gelatin and fibrin glue hemostatic materials mainly affect the physiological coagulation mechanism of the human body to stop bleeding, suitable for people with normal coagulation function. Reasonable selection of MAHM can effectively reduce perioperative blood loss and reduce the risk of postoperative complications, but at present, single hemostatic material can not meet clinical needs, and a new composite hemostatic material with higher hemostatic efficiency needs to be developed.

A glutamine metabolic switch supports erythropoiesis.

Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production. Loss of GS in mouse erythroid precursors caused ammonium accumulation and oxidative stress, impairing erythroid maturation and recovery from anemia. In β-thalassemia, GS activity is inhibited by protein oxidation, leading to glutamate and ammonium accumulation, whereas enhancing GS activity alleviates the metabolic and pathological defects. Our findings identify an evolutionarily conserved metabolic adaptation that could potentially be leveraged to treat common red blood cell disorders.