Search

Miliary tuberculosis is a form of disseminated tuberculosis that can be difficult to detect when the classic pattern is absent on chest radiograph and advanced cross-sectional imaging is not readily available. While the focused assessment with sonography for HIV-associated tuberculosis (FASH) protocol for extrapulmonary tuberculosis emphasizes easy-to-teach findings, experienced sonographers may detect additional, subtler signs that can aid in diagnosis. We report a case of a 20-year-old man with miliary tuberculosis diagnosed on computed tomography of the chest. We describe subtle sonographic signs of disseminated tuberculosis including subpleural irregularities and comet-tail artifacts, a bright liver pattern, peritoneal nodules, and a nonspecific sponge spleen pattern. We then discuss important differential diagnoses for each finding. Knowledge of subtle sonographic signs outside of the FASH protocol can aid clinicians in detecting disseminated tuberculosis, including the miliary form, when advanced imaging may not be available.

BACKGROUND: Early initiation of venous thromboembolism (VTE) chemoprophylaxis in adults with blunt solid organ injury (BSOI) has been demonstrated to be safe but this is controversial in adolescents. We hypothesized that adolescent patients with BSOI undergoing non-operative management (NOM) and receiving early VTE chemoprophylaxis (eVTEP) (≤ 48 h) have a decreased rate of VTE and similar rate of failure of NOM, compared to similarly matched adolescents receiving delayed VTE chemoprophylaxis (dVTEP) (> 48 h). METHODS: The 2017-2019 Trauma Quality Improvement Program database was queried for adolescents (12-17 years of age) with BSOI (liver, kidney, and/or spleen) undergoing NOM. We compared eVTEP versus dVTEP using a 1:1 propensity score model, matching for age, comorbidities, BSOI grade, injury severity score, hypotension on arrival, and need for transfusions. We performed subset analyses in patients with isolated spleen, kidney, and liver injury. RESULTS: From 1022 cases, 417 (40.8%) adolescents received eVTEP. After matching, there was no difference in matched variables (all p > 0.05). Both groups had a similar rate of VTE (dVTEP 0.6% vs. eVTEP 1.7%, p = 0.16), mortality (dVTEP 0.3% vs. eVTEP 0%, p = 0.32), and failure of NOM (eVTEP 6.7% vs. dVTEP 7.3%, p = 0.77). These findings remained true in all subset analyses of isolated solid organ injury (all p > 0.05). CONCLUSIONS: The rate of VTE with adolescent BSOI is exceedingly rare. Early VTE chemoprophylaxis in adolescent BSOI does not increase the rate of failing NOM. However, unlike adult trauma patients, adolescent patients with BSOI receiving eVTEP had a similar rate of VTE and death, compared to adolescents receiving dVTEP.

Infectious bronchitis virus (IBV) induces severe economic losses in chicken farms due to the emergence of new variants leading to vaccine breaks. The studied IBV strains belong to Massachusetts (Mass), Canadian 4/91, and California (Cal) 1737 genotypes that are prevalent globally. This study was designed to compare the impact of these three IBV genotypes on primary and secondary lymphoid organs. For this purpose, one-week-old specific pathogen-free chickens were inoculated with Mass, Canadian 4/91, or Cal 1737 IBV variants, keeping a mock-infected control. We examined the IBV replication in primary and secondary lymphoid organs. The molecular, histopathological, and immunohistochemical examinations revealed significant differences in lesion scores and viral distribution in these immune organs. In addition, we observed B-cell depletion in the bursa of Fabricius and the spleen with a significant elevation of T cells in these organs. Further studies are required to determine the functional consequences of IBV replication in lymphoid organs.

OBJECTIVES: There is little evidence guiding the management of grade I-II traumatic splenic injuries with contrast blush (CB). We aimed to analyze the failure rate of nonoperative management (NOM) of grade I-II splenic injuries with CB in hemodynamically stable patients. METHODS: A multicenter, retrospective cohort study examining all grade I-II splenic injuries with CB was performed at 21 institutions from January 1, 2014, to October 31, 2019. Patients >18 years old with grade I or II splenic injury due to blunt trauma with CB on CT were included. The primary outcome was the failure of NOM requiring angioembolization/operation. We determined the failure rate of NOM for grade I versus grade II splenic injuries. We then performed bivariate comparisons of patients who failed NOM with those who did not. RESULTS: A total of 145 patients were included. Median Injury Severity Score was 17. The combined rate of failure for grade I-II injuries was 20.0%. There was no statistical difference in failure of NOM between grade I and II injuries with CB (18.2% vs 21.1%, p>0.05). Patients who failed NOM had an increased median hospital length of stay (p=0.024) and increased need for blood transfusion (p=0.004) and massive transfusion (p=0.030). Five patients (3.4%) died and 96 (66.2%) were discharged home, with no differences between those who failed and those who did not fail NOM (both p>0.05). CONCLUSION: NOM of grade I-II splenic injuries with CB fails in 20% of patients. LEVEL OF EVIDENCE: IV.

Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55+ beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.

Purpose: Systemic immunity is essential for driving therapeutically induced antitumor immune responses, and the spleen may reflect alterations in systemic immunity. This study aimed to evaluate the predictive value of contrast-enhanced CT-based spleen radiomics for progression-free survival (PFS) in patients with locally advanced cervical cancer (LACC) who underwent definitive chemoradiotherapy (dCRT). Additionally, we investigated the role of spleen radiomics features and changes in spleen volume in assessing systemic immunity. Methods: This retrospective study included 257 patients with LACC who underwent dCRT. The patients were randomly divided into training and validation groups in a 7:3 ratio. Radiomic features were extracted from CT images obtained before and after dCRT. Radiomic scores (Radscore) were calculated using features selected through least absolute shrinkage and selection operator (LASSO) Cox regression. The percentage change in spleen volume was determined from measurements taken before and after treatment. Independent prognostic factors for PFS were identified through multivariate Cox regression analyses. Model performance was evaluated with the receiver operating characteristic (ROC) curve and the C-index. The Radscore cut-off value, determined from the ROC curve, was used to stratify patients into high- and low-risk survival groups. The Wilcoxon test was used to analyze differences in hematological parameters between different survival risk groups and between different spleen volume change groups. Spearman correlation analysis was used to explore the relationship between spleen volume change and hematological parameters. Results: Independent prognostic factors included FIGO stage, pre-treatment neutrophil-to-lymphocyte ratio (pre-NLR), spleen volume change, and Radscore. The radiomics-combined model demonstrated the best predictive performance for PFS in both the training group (AUC: 0.923, C-index: 0.884) and the validation group (AUC: 0.895, C-index: 0.834). Compared to the low-risk group, the high-risk group had higher pre-NLR (p = 0.0054) and post-NLR (p = 0.038). Additionally, compared to the decreased spleen volume group, the increased spleen volume group had lower post-NLR (p = 0.0059) and post-treatment platelet-to-lymphocyte ratio (p < 0.001). Conclusion: Spleen radiomics combined with clinical features can effectively predict PFS in patients with LACC after dCRT. Furthermore, spleen radiomics features and changes in spleen volume can reflect alterations in systemic immunity. [ABSTRACT FROM AUTHOR]

Splenic hemangioma is a rare benign tumor, often found incidentally. Large hemangiomas bear a high risk of spontaneous rupture, an acute condition often life-threatening that requires immediate intervention. The spleen's vital role in immunity and blood filtration mandates organ-preserving management of conditions such as hypersplenism or large lesions such as hemangiomas. A 51-year-old patient was referred to our department for abdominal pain due to a giant spleen hemangioma (6,6 × 6,3 × 5,6) cm in size. The patient was treated with hemangioma embolization through the splenic artery branches that fed the lesion, without any complications. Two years post-embolization the patient mentioned no symptoms and the hemangioma was measured (3 × 2) cm. Background The patient was referred to our department due to the large size of the lesion and the patient's preference to avoid surgery and maintain the spleen. Our case report aims to underline (a) the safety and feasibility of the protocol among interventional radiologists, surgeons, and patients, (b) the benefit of relieving symptoms without losing a vital organ, and (c) the lower complication rate and hospital days compared with surgery. There are few reported cases of embolization of large spleen hemangioma. While Choi et al. (BMC Pediatr. 2018 12;18(1):354) report a similar case in a child. This case report describes the procedure in a stable adult and provides a 2-year follow-up. [ABSTRACT FROM AUTHOR]

Background: Obsidio conformable embolic (OCE, Boston Scientific, MA) is a novel, radiopaque and conformable embolic. The purpose of this report is to describe its use for treatment of acute intra-abdominal hemorrhages. Methods and results: Three patients presented with acute hemorrhage and were treated with OCE, including post-paracentesis hemorrhage, penetrating trauma to the liver, and blunt trauma in the spleen. All cases were performed under moderate sedation, with hemostasis achieved by end of procedure using less than 1 vial of OCE (0.2-0.4 ml). No severe adverse events occurred. None required repeated treatment. Short conclusion: OCE is a safe and effective embolic agent for treatment of intra-abdominal or visceral hemorrhage. Future studies with larger sample sizes and longer follow-up are warranted. [ABSTRACT FROM AUTHOR]

Comprehensive characterization of AML-associated T cells during disease progression is essential to identify relevant immune escape mechanisms and new immunotherapeutic approaches. Investigating the processes that lead to an immunosuppressive environment under progression of AML is difficult in humans, because by the time of diagnosis the disease is often progressed far beyond the initial stages. Therefore, to investigate T-cell phenotypes during progression a C57BL/6 mouse model was used. The CD3+ T cells were characterized by performing multiparametric flow analyses at different time points (day 0 = healthy mice, day 7, day 14, and day 21). The study revealed that the spleen is highly infiltrated by reg CD4+ T cells at day 21 of AML progression. These spleen-infiltrating reg CD4+ T cells mainly showed an effector memory differentiation with high expression and co-expression of the checkpoint molecules TIGIT, PD-1, OX40, and the two ectoenzymes CD39 and CD73. Substantial expression of the checkpoint molecules was restricted to the central memory and effector memory compartments. Furthermore, functional evaluation of TIGIT was performed. Blocking TIGIT resulted in a significantly increased lysis of C1498 AML cells in cocultures with AML-primed CD3+ T cells. Together these data confirm that the expression of the checkpoint receptor TIGIT is relevant for dysfunction of AML-associated T cells and, thus, represents a suitable target for future immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to evaluate the indocyanine green (ICG) retention test as a noninvasive marker of esophageal varices(EV). Methods: The clinical data of patients diagnosed with compensated liver cirrhosis in Tianjin Second People's Hospital between January 2018 and January 2021 were analysed with SPSS 23.0. Result: A total of 144 patients (88 M/56 F, 51.7 ± 11.06 years) were enrolled. The ICG retention at 15 min(ICG-r15), PVD, TBIL, Cholinesterase(CHE), AST to ALT ratio(ARR), APRI, splenic area, Lok index, Park index and liver stiffness measurement in the absent or small EV group were lower than those in the medium or large EV group, while the ICG disappareance rate(ICG-K), Effective hepatic blood flow(EHBF), ALB, PLT, and Platelet to Spleen Diameter Ratio(PSDR) were higher, and the differences were significant (P < 0.05). ICG-r15, splenic area, APRI and PLT were independent predictors for medium or large esophageal varices (OR = 1.115, 1.025, 0.281, and 0.987, respectively,P < 0.05). The predictive value of ICG-r15 for medium or large varices was 17.95%, the specificity was 0.849, and the sensitivity was 0.662, the AUROC was 0.815. The cut-off value of PLT for M/L EV was 113.5, and the specificity and sensitivity were 0.616 and 0.887, the AUROC was 0.759. The AUROC of ICG-r15 combined with PLT was 0.866, which was more superior than others. Conclusion: Although we are far from the replacement of endoscopy, ICG-r15 combined with PLT seems to be able to identify patients with medium or large EV in patients with compensated liver cirrhosis. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic performance of post-contrast CT for predicting moderate hepatic steatosis in an older adult cohort undergoing a uniform CT protocol, utilizing hepatic and splenic attenuation values. Materials and methods: A total of 1676 adults (mean age, 68.4 ± 10.2 years; 1045M/631F) underwent a CT urothelial protocol that included unenhanced, portal venous, and 10-min delayed phases through the liver and spleen. Automated hepatosplenic segmentation for attenuation values (in HU) was performed using a validated deep-learning tool. Unenhanced liver attenuation < 40.0 HU, corresponding to > 15% MRI-based proton density fat, served as the reference standard for moderate steatosis. Results: The prevalence of moderate or severe steatosis was 12.9% (216/1676). The diagnostic performance of portal venous liver HU in predicting moderate hepatic steatosis (AUROC = 0.943) was significantly better than the liver–spleen HU difference (AUROC = 0.814) (p < 0.001). Portal venous phase liver thresholds of 80 and 90 HU had a sensitivity/specificity for moderate steatosis of 85.6%/89.6%, and 94.9%/74.7%, respectively, whereas a liver–spleen difference of −40 HU and −10 HU had a sensitivity/specificity of 43.5%/90.0% and 92.1%/52.5%, respectively. Furthermore, livers with moderate–severe steatosis demonstrated significantly less post-contrast enhancement (mean, 35.7 HU vs 47.3 HU; p < 0.001). Conclusion: Moderate steatosis can be reliably diagnosed on standard portal venous phase CT using liver attenuation values alone. Consideration of splenic attenuation appears to add little value. Moderate steatosis not only has intrinsically lower pre-contrast liver attenuation values (< 40 HU), but also enhances less, typically resulting in post-contrast liver attenuation values of 80 HU or less. Clinical relevance statement: Moderate steatosis can be reliably diagnosed on post-contrast CT using liver attenuation values alone. Livers with at least moderate steatosis enhance less than those with mild or no steatosis, which combines with the lower intrinsic attenuation to improve detection. Key Points: The liver–spleen attenuation difference is frequently utilized in routine practice but appears to have performance limitations. The liver–spleen attenuation difference is less effective than liver attenuation for moderate steatosis. Moderate and severe steatosis can be identified on standard portal venous phase CT using liver attenuation alone. [ABSTRACT FROM AUTHOR]

The regulatory role of estrogen receptor beta (ERβ) and the JNK signaling pathway in the effect of high-dose boron on rat splenic lymphocytes has been examined by measuring proliferation, apoptosis, and immune function. The results showed that, compared with the control group, the addition of high-dose boron (40 mmol/L) reduced the proportion of CD3+, CD4+, and CD8+ T lymphocytes, the concentrations of IgG, IL-2, IFN-γ, and IL-4, the proliferation rate of splenic lymphocytes, and the expression levels of PCNA and Bcl-2 mRNA (P < 0.01 or P < 0.05), and increased the apoptosis rate of splenic lymphocytes, caspase-3, and BAX mRNA expression levels (P < 0.01 or P < 0.05). After specific blocking of ERβ, the addition of high-dose boron could not reduce the proportion of CD8+ T lymphocytes, the concentrations of IgG and cytokines IL-2, IFN-γ, and IL-4, the lymphocyte proliferation rate, or PCNA mRNA expression levels, nor could it increase BAX mRNA expression levels. After specific blocking of JNK, the addition of high-dose boron could not increase BAX mRNA expression levels. However, after specific blocking of ERβ and JNK, the addition of high-dose boron could neither reduce the proportion of CD4+ and CD8+ T lymphocytes, the concentrations of IgG and IL-2 (P > 0.05), nor increase caspase-3 and BAX mRNA expression levels (P < 0.01). The results suggest that the ERβ-mediated JNK signaling pathway participates in regulating the effects of high-dose boron on the expression of genes related to the proliferation and apoptosis of rat splenic lymphocytes. [ABSTRACT FROM AUTHOR]

In this study, a ddPCR method for the detection of scale drop disease virus (SDDV) in yellowfin seabream (Acanthopagrus latus) was established based on Real-time fluorescence quantitative PCR detection methods and principles. The reaction conditions were optimized, and the sensitivity, specificity, accuracy, and reproducibility were assessed. The results showed that threshold line position was determined to be 1900 by the ddPCR method; the optimum annealing temperature for SDDV detection by the ddPCR method was 60°C; the limit of detection was 1.4-1.7 copies/µL; the results of specific detection of other common viruses, except for SDDV specific amplification, were all negative; and the relative standard deviation (RSD) for the reproducibility validation was 0.77%. The samples of yellowfin seabream (Acanthopagrus latus) liver, spleen, kidney, heart, intestine, brain, blood, muscle, skin and ascites with three replicates, respectively, were tested using the ddPCR method, and the results were consistent with clinical findings. The ddPCR method established in this study has the advantages of high sensitivity, high specificity, good reproducibility and simple steps for the quantitative detection of SDDV, which could be used for the nucleic acid detection of clinical SDDV samples, and provided a new quantitative method for the diagnosis of yellowfin seabream SDDV in the early stage of pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Ultrasonography is an established and reliable method for assessing the spleen. Because of variation due to genetic and other environmental factors including malaria endemicity, interpretation of spleen sizes requires a knowledge of the normal reference range for a given population. This study aimed to identify spleen size reference ranges across age groups of healthy controls to serve as a baseline to assess changes in spleen size in patients with sickle cell disease. Methods: Using a cross-sectional study design, spleen size was measured in healthy people of different age groups and steady-state sickle cell disease patients (children and adults) using abdominal ultrasonography. Using the age-group-specific reference values obtained from the controls, spleens were classified into small, normal size or enlarged among the sickle cell disease patients. Results: The study consisted of 109 (34.8%) healthy controls and 204 (65.2%) steady-state sickle cell disease patients. The spleen was visualised in all the controls (n = 109) and in 107 (52.4%) sickle cell disease patients. Using cut-off values for spleen length among the controls across age groups (< 5 years (5.0–7.0 cm); 5–9 years (5.5–8.5 cm); 10–14 years (6.0–11.0 cm) and ⩾ 15 years (7.0–12.5 cm)), spleen size was classified as small (n = 18/204; 8.87%), normal (n = 68/204; 33.3%) and enlarged (n = 21/204; 10.3%) among the sickle cell disease patients. Conclusion: Model-based age-group reference ranges and percentile curves for splenic dimensions based on ultrasonography among normal controls in North-Eastern Nigeria were established and may be of value in assessing spleen sizes among sickle cell disease patients living in malaria-endemic regions of Africa. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) have been demonstrated to be potent and well‐tolerated vehicles for delivering mRNA in vaccination and therapeutics. However, the presence of anti‐poly(ethylene glycol) (PEG) antibodies in the body resulted in the problems of hypersensitivity reaction, accelerated blood clearance and high systemic reactogenicity after repeated dosing of PEG lipid‐contained LNPs, thus limiting the utility for in vivo messenger RNA (mRNA) delivery. Here, we synthesized well‐defined polysarcosine functionalized lipids (pSar‐lipids) with various hydrophobic tail lengths and molecular weights by the accelerated ring‐opening polymerization of sarcosine N‐carboxyanhydride (NCA). The obtained pSar‐lipids were utilized as PEG lipid alternatives to explore structure–activity relationships of pSar‐lipid‐based LNPs. The results demonstrated that pSar‐lipid‐based LNPs by intravenous administration represented higher mRNA delivery efficiency in the liver and spleen with the increased hydrophobic tail length of pSar‐lipids. Importantly, more significant preference for mRNA delivery into the liver was identified by increasing the molecular weight of pSar segments. As a result, this work elucidated the effect of structural variations in pSar‐lipids on LNP‐mediated in vivo mRNA delivery, providing clues to optimize pSar‐lipids as potential alternatives to PEG lipids for developing next‐generation of LNP delivery systems. [ABSTRACT FROM AUTHOR]

This study investigated the effects of Enterococcus hirae (Eh) derived from Ningxiang pigs on growth performance, diarrhea incidence, and immune responses in ETEC-challenged piglets. The results showed that compared to the CON group, ETEC infection significantly reduced the average daily gain (ADG) and average daily feed intake (ADFI), increased rectal temperature, and resulted in a diarrhea rate of up to 24%. Additionally, ETEC infection significantly increased the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of piglets. Compared to the ETEC group, orally Eh significantly increased ADFI in ETEC-infected piglets, reduced the diarrhea rate to 11.53%, reduced the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of ETEC-infected piglets. Furthermore, correlation analysis revealed that the levels of SCFAs (particularly acetate) were significantly negatively correlated with the expression levels of inflammatory cytokines in colonic and splenic tissues, suggesting that acetate may be a key metabolite in the anti-inflammatory effects of Eh. These results indicate that Eh can enhance the protection of piglets against ETEC K88 via intestine-acetate-spleen axis, thereby alleviating diarrhea and improving growth performance in piglets. [ABSTRACT FROM AUTHOR]

Background: Spleen abscess is a rare and serious condition. Splenectomy and imaging-guided percutaneous catheter drainage (PCD) are the methods used in the treatment, but there is still a debate about the appropriate treatment for the patient. Methods: The results of 16 patients treated for spleen abscesses in our clinic between 2012 and 2021 were reviewed. The patients were divided into two groups according to splenectomy and PCD. Results: In the study, PCD was performed in 11 patients (68.75%), but three of these patients required splenectomy due to inadequate drainage. The patients who underwent splenectomy were significantly younger than the patients who underwent PCD (p < 0.05). One patient underwent PCD and 2 patients underwent splenectomy after PCD died. Conclusion: Spleen abscess is a serious clinical picture that requires a multidisciplinary approach and is life-threatening. New clinical studies are needed for a treatment algorithm that will provide good results. [ABSTRACT FROM AUTHOR]

Copper (Cu) is a necessary micro-element and plays important roles in many biochemical processes. However, excessive Cu intake can lead to multi-organ toxicity, especially in the spleen. To gain further insights into the specific mechanisms of splenic toxicity associated with Cu-induced metabolic disorders, 192 one-day-old chickens were selected and randomly divided into four groups for this study. The broilers were fed with diets containing Cu at final concentrations of 11, 110, 220 and 330 mg/kg for 49 days. The results showed that high dietary Cu caused nuclear shrinkage and mitochondrial vacuolization in the spleen and induced splenic injury through regulating the glutathione metabolism, pentose and gluconate interconversion, tryptophan metabolism and glycerophosphatidylcholine metabolism pathways. Moreover, excess Cu could disorder the mitochondrial dynamics via up-regulating the levels of Drp1, Parkin PINK1, and Dynein, and down-regulating the levels of Mfn1, Mfn2 and OPA1. Cu treatment increased the levels of LC3A, LC3B, mTOR, Beclin1, and ATG5 and decreased the p62 level to promote autophagy of splenocytes. Meanwhile, a high dose of Cu promoted splenocyte apoptosis by increasing the levels of p53, BAK-1, Bax, Cyt C and Caspase-3 and decreasing the level of Bcl-2. These results demonstrated that high dietary Cu could cause autophagy and apoptosis via inducing metabolic disturbances and disordering mitochondrial dynamics in the spleen of broiler chicken. [ABSTRACT FROM AUTHOR]

Background: Diarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites. Methods: The new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model (3 groups) rats were prepared articially using mother's separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16 S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database. Results: Significant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P < 0.05) after treatment with FMT and TCM. FMT and TCM altered the gut microbiota and regulated the tryptophan metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism of IBS-D rats with spleen deficiency syndrome.The microbial abundance were changed in each case e.g., Monoglobus, Dubosiella, and Akkermansia and othe metabolic profiles. Conclusion: FMT and TCM treatment improved the intestinal barrier function by regulating gut microbiota and improved metabolic pathways in IBS-D with spleen deficiency syndrome. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Radix Astragali, commonly known as Astragalus, is a traditional medicinal and edible plant valued for its Qi‐tonifying properties. The dosage form of Radix Astragali processed with honey, known as honey‐processed Astragalus (HPA), shows improved Qi‐tonifying efficacy as compared to the raw product. Polysaccharides are the main bioactive ingredients in its aqueous extract. This study used a multiomics approach integrating microbiomics and metabolomics to elucidate the Qi‐tonifying mechanisms of honey‐processed Astragalus polysaccharides (HAPS).HAPS‐treated mice showed improved symptom scores, spleen and thymus indices, serum cytokines (tumor necrosis factor α, interleukin 1β) and intestinal mucosa secretory immunoglobulin A (SIgA) compared to the mice with spleen Qi deficiency. The analysis of gut microbiota indicated that HAPS regulated the relative abundance of Bacteroidetes, Bacteroides, Proteobacteria and Helicobacter, thereby improving intestinal flora dysbiosis in mice with spleen Qi deficiency. Eleven biomarkers in fecal metabolomics analysis were screened and identified, primarily associated with linoleic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. Furthermore, comprehensive analyses demonstrated that HAPS regulates palmitic acid and sphingolipid metabolism by modulating the abundance of Bacteroidetes, which in turn increased the levels of intestinal mucosal SIgA and restored intestinal mucosal immune function in mice with spleen Qi deficiency.Our findings revealed that HAPS is an essential active ingredient of HPA, and its Qi‐tonifying mechanism is closely related to the improvement of intestinal immune function. These findings lay the foundation for the application of HAPS as an immunomodulatory agent in health and dietary foods. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In this paper, active polysaccharides were extracted from Brassica rapa L. polysaccharide (BRP), and structural characterization was preliminarily investigated. Its immunomodulatory activity and molecular biological mechanisms in cyclophosphamide‐induced immunosuppressed mice were also explored, as well as its effects on intestinal microbiota. Results indicate that BRP is an acidic heteropolysaccharide with the main components of Ara, GalA, and GlcA and has α‐ and β‐glycosidic linkages with pyranose bonds. The results of the study showed that BRP could effectively improve the thymus and spleen indices and repair Cy‐induced immune tissue damage in immunosuppressed mice. Meanwhile, BRP increased the immune cell activity and antioxidant levels in mice. In addition, BRP increased the secretion of cytokines (IL‐1β, IL‐6, IL‐10, and TNF‐α) and immunoglobulins (IgA, IgG) in mouse serum. It also regulates the relative expression of genes related to the TLR4/NF‐κB signaling pathways as well as regulates the diversity and composition of mouse intestinal microbiota. In conclusion, BRP was able to regulated the immune function in immunosuppressed mice, providing a theoretical basis for the development of immunomodulators. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of xylo-oligosaccharides on intestinal bacterial diversity in mice with spleen deficiency constipation. Methods: The 16S rDNA sequencing was used to identify microbiota composition in four groups, including the normal group (NG), the model group with spleen-deficiency constipation (SDC), XOS treated groups that include XOS1 groups treated XOS 0.05 g/mL•d, and XOS2 group treated XOS 0.1g/mL•d. Chao1 and Shannon were used to conduct gut microbes diversity analysis. Linear discriminant analysis coupled with effect size measurements (LEfSe) was used to identify signature gut microbiota, and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict the function of altered gut microbiota. Results: Veen map indicated 245 common OTUs were identified from four groups. Especially, 9, 3, 0, and 19 unique OTUs were identified in NG, SDC, XOS1, and XOS2 groups, respectively. The Shannon index was evidently higher in NG group than in the other three groups (p<0.05). We identified the occurrence of dominant bacterial groups including Bacteroidetes (25.5 ~ 49.9%), Firmicutes (25.4 ~ 39.3%), Proteobacteria (12.5 ~ 24.9%), Deferribacteres (1.6 ~ 19.2%), Cyanobacteria (0.3 ~ 1.8%), Verrucomicrobia (0.02 ~ 1.6%), Actinobacteria (0.01~0.5%), and Tenericutes (0.03 ~ 0.09%) at the four groups. The XOS2 group was characterized by a higher abundance of Peptostreptococcaceae, Intestinibacter, Aerococcaceae, and Facklamia. XOS1 group enriched in Deferribacteres, Mucispirillum, Deferribacterales, Deferribacteres, Lachnoclostridium, Rhodospirillaceae, and Rhodospirillales. Meanwhile, the SDC mice showed dramatic enrichment in Rikenellaceae, Lachnospiraceae, Rikenellaceae, Roseburia, and Alistipes, which were highly abundant in the NG group. XOS fed-mice evidently increase Deferribcteres abundance compared with NG and SDC groups. However, the abundance of Rikenellaceae was significantly reduced in XOS1 and XOS2 groups compared with NG and SDC groups. We identified that altered gut microbiotas by XOS treatment were associated with various metabolic pathways, including organismal systems, metabolism, human diseases, genetic information processing, and cellular processes. Conclusion: Our research indicated that XOS has the potential to recover intestinal bacteria and contribute to the treatment of spleen deficiency constipation. [ABSTRACT FROM AUTHOR]

Background: Rebleeding after endoscopic treatment for esophagogastric varices (EGVs) in cirrhotic patients remains a significant clinical challenge, with high mortality rates and limited predictive tools. Current methods, relying on clinical indicators, often lack precision and fail to provide personalized risk assessments. This study aims to develop and validate a novel, non-invasive prediction model based on CT radiomics to predict rebleeding risk within one year of treatment, integrating radiomic features from key organs and clinical data. Methods: 123 patients were enrolled and divided into rebleeding (n = 44) and non-bleeding group (n = 79) within 1 year after endoscopic treatment of EGVs. The liver, spleen, and the lower part of the esophagus were segmented and the extracted radiomics features were selected to construct liver/spleen/esophagus radiomics signatures based on logistic regression. Clinic-radiomics combined models and multi-organ combined radiomics models were constructed based on independent model scores using logistic regression. The model performance was evaluated by ROC analysis, calibration and decision curves. The continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices were analyzed. Results: The clinical-liver combined model had the highest AUC of 0.931 (95% CI: 0.887–0.974), which was followed by the liver-based model with AUC of 0.891 (95% CI: 0.835–0.74). The decision curves also showed that the clinical-liver combined model afforded a greater net benefit compared to other models within the threshold probability of 0.45 to 0.80. Significant improvements in discrimination (IDI, P < 0.05) and reclassification (NRI, P < 0.05) were obtained for clinical-liver combined model compared with the independent ones. Conclusion: The independent and combined liver-based CT radiomics models performed well in predicting rebleeding within 1 year after endoscopic treatment of EGVs. [ABSTRACT FROM AUTHOR]

Myelofibrosis (MF) is a complex myeloproliferative neoplasm characterized by abnormal hematopoietic stem cell proliferation and subsequent bone marrow (BM) fibrosis. First documented in the late 19th century, MF has since been extensively studied to unravel its pathophysiology, clinical phenotypes, and therapeutic interventions. MF can be classified into primary and secondary forms, both driven by mutations in genes such as JAK2, CALR, and MPL, which activate the JAK-STAT signaling pathway. These driver mutations are frequently accompanied by additional non-driver mutations in genes like TET2, SRSF2, and TP53, contributing to disease complexity. The BM microenvironment, consisting of stromal cells, extracellular matrix, and cytokines such as TGF-β and TNF-α, plays a critical role in fibrosis and aberrant hematopoiesis. Clinically, MF manifests with symptoms ranging from anemia, splenomegaly, and fatigue to severe complications such as leukemic transformation. Splenomegaly, caused by extramedullary hematopoiesis, leads to abdominal discomfort and early satiety. Current therapeutic strategies include JAK inhibitors like Ruxolitinib, which target the JAK-STAT pathway, alongside supportive treatments such as blood transfusions, erythropoiesis-stimulating agents and developing combinatorial approaches. Allogeneic hematopoietic stem cell transplantation remains the only curative option, though it is limited to younger, high-risk patients. Recently approved JAK inhibitors, including Fedratinib, Pacritinib, and Momelotinib, have expanded the therapeutic landscape. Spatially Resolved Transcriptomics (SRT) has revolutionized the study of gene expression within the spatial context of tissues, providing unprecedented insights into cellular heterogeneity, spatial gene regulation, and microenvironmental interactions, including stromal-hematopoietic dynamics. SRT enables high-resolution mapping of gene expression in the BM and spleen, revealing molecular signatures, spatial heterogeneity, and pathological niches that drive disease progression. These technologies elucidate the role of the spleen in MF, highlighting its transformation into a site of abnormal hematopoietic activity, fibrotic changes, and immune cell infiltration, functioning as a "tumor surrogate." By profiling diverse cell populations and molecular alterations within the BM and spleen, SRT facilitates a deeper understanding of MF pathophysiology, helping identify novel therapeutic targets and biomarkers. Ultimately, integrating spatial transcriptomics into MF research promises to enhance diagnostic precision and therapeutic innovation, addressing the multifaceted challenges of this disease. [ABSTRACT FROM AUTHOR]

Background: Trichomoniasis caused by Trichomonas vaginalis is the most prevalent nonviral sexually transmitted disease in women and has frequently damaged public health. To better use the animal model and take a step forward fully elucidating this pathogen, intraperitoneal infection of T. vaginalis in mice, one of the most common mouse models, was highly concerned. Methods: By adjusting the number of parasites inoculated, acute and chronic infection models were established. Pathological changes and the presence of T. vaginalis in organs were observed at different timepoints post inoculation using histological and TV-α-actinin-based immunological detection. Results: The results reconfirmed the correlation between inoculum size of parasites and infection duration, as well as the multiplication capacity of T. vaginalis in mouse enterocoelia or invaded organs. The progression and pathologic features of vital organs (e.g., liver and spleen) from mice intraperitoneally infected with T. vaginalis in both the acute and chronic groups were also revealed. In particular, a reliable immunological method based on TV-α-actinin was first verified to clearly present the invasion of T. vaginalis into infected mouse organs. Conclusions: In brief, this study presented a clearer and more detailed pathologic characteristic of the intraperitoneal infection model, which probably provides more basic information for the use of this model in future studies. Especially, expanding on specific research applications of this model would be valuable. [ABSTRACT FROM AUTHOR]

Purpose: Tissue radiotracer activity measured from positron emission tomography (PET) images is an important biomarker that is clinically utilized for diagnosis, staging, prognostication, and treatment response assessment in patients with cancer and other clinical disorders. Using PET image values to define a normal range of metabolic activity for quantification purposes is challenging due to variations in patient-related factors and technical factors. Although the formulation of standardized uptake value (SUV) has compensated for some of these variabilities, significant non-standardness still persists. We propose an image processing method to substantially mitigate these variabilities. Methods: The standardization method is similar for activity concentration (AC) PET and SUV PET images, with some differences, and consists of two steps. The calibration step is performed only once for both AC PET or SUV PET, employs a set of images of normal subjects, and requires a reference object, while the transformation step is executed for each patient image to be standardized. In the calibration step, a standardized scale is determined along with 3 key image intensity landmarks defined on it: the minimum percentile intensity smin, median intensity sm, and high percentile intensity smax. smin and sm are estimated based on image intensities within the body region in the normal calibration image set. The optimal value of the maximum percentile β corresponding to the intensity smax is estimated via an optimization process by using the reference object to optimally separate the highly variable high uptake values from the normal uptake intensities. In the transformation step, the first two landmarks--the minimum percentile intensity pα(I), and the median intensity pm(I)--are found for the given image I for the body region, and the high percentile intensity pβ(I) is determined corresponding to the optimally estimated high percentile value β. Subsequently, intensities of I are mapped to the standard scale piecewise linearly for different segments. We employ three strategies for evaluation and comparison with other standardization methods: (i) comparing coefficient of variation (CVO) of mean intensity within test objects O across different normal test subjects before and after standardization, (ii) comparing mean absolute difference (MDO) of mean intensity within test objects O across different subjects in repeat scans before and after standardization, and (iii) comparing CVO of mean intensity across different normal subjects before and after standardization where the scans came from different brands of scanners. Results: Our data set consisted of 84 FDG-PET/CT scans of the body torso including 38 normal subjects and two repeat-scans of 23 patients. We utilized one of two objects--liver and spleen--as a reference object and the other for testing. The proposed standardization method reduced CVO and MDO by a factor of 3-8 in comparison to other standardization methods and no standardization. Upon standardization by our method, the image intensities (both for AC and SUV) from two different brands of scanners become statistically indistinguishable, while without standardization, they differ significantly and by a factor of 3-9. Conclusions: The proposed method is automatic, outperforms current standardization methods, and effectively overcomes the residual variation left over in SUV and interscanner variations. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Single Photon Emission Computed Tomography (SPECT) sinogram restoration for low‐dose imaging is a critical challenge in medical imaging. Existing methods often overlook the characteristics of the sinograms, necessitating innovative approaches.In this study, we introduce the Sinogram‐characteristic‐informed network (SCI‐Net) to address the restoration of low‐dose SPECT sinograms. Our aim is to build and train a model based on the characteristics of sinograms, including continuity, periodicity, multi‐scale properties of lines in sinograms, and others, to enhance the model's understanding of the restoration process.SCI‐Net incorporates several novel mechanisms tailored to exploit the inherent characteristics of sinograms. We implement a channel attention module with a decay mechanism to leverage continuity across adjacent sinograms, while a position attention module captures global correlations within individual sinograms. Additionally, we propose a multi‐stage progressive integration mechanism to balance local detail and overall structure. Multiple regularization terms, customized to sinogram image characteristics, are embedded into the loss function for model training.The experimental evaluations are divided into two parts: simulation data evaluation and clinical evaluation. The simulation data evaluation is conducted on a dataset comprising ten organ types, generated by the SIMIND Monte Carlo program from extended cardiac‐torso (XCAT) anatomical phantoms. The dataset includes a total of SPECT sinograms with low‐dose as input data and normal‐dose as ground truth, consisting of 3881 sinograms in the training dataset and 849 sinograms in the testing set. When comparing the restoration of low‐dose sinograms to normal‐dose references, SCI‐Net effectively improves performance. Specifically, the peak signal‐to‐noise ratio (PSNR) and the structural similarity (SSIM) on sinograms increase from 15.72 to 34.66 (p<$\text{p}< $ 0.001) and 0.6297 to 0.9834 (p<$\text{p}<$ 0.001), respectively, and on reconstructed images, reconstructed by maximum likelihood‐expectation maximization (ML‐EM), the PSNR and the SSIM improve from 21.95 to 33.14 (p<$\text{p}<$ 0.001) and 0.9084 to 0.9866 (p<$\text{p}<$ 0.001), respectively. We compared SCI‐Net with existing methods, including baseline models, traditional reconstruction algorithms, end‐to‐end methods, sinogram restoration methods, and image post‐processing methods. The experimental results and visual examples demonstrate that SCI‐Net surpasses these existing methods in SPECT sinogram restoration. The clinical evaluation is conducted on clinical data of low‐dose SPECT sinograms for spleen, thyroid, skull, and bone. These SPECT projection data are obtained from Discovery NM/CT670 scans. We compare the reconstructed images from the SCI‐Net restored sinograms, the reconstructed images from the original low‐dose sinograms, and the reconstructed images using the built‐in algorithm of the Discovery NM/CT670. The results show that our method effectively reduces the coefficient of variation (COV) in the regions of interest (ROI) of the reconstructed images, thereby enhancing the quality of the reconstructed images through SPECT sinogram restoration.Our proposed SCI‐Net exhibits promising performance in the restoration of low‐dose SPECT projection data. In the SCI‐Net, we have implemented three mechanisms based on distinct forms, which are advantageous for the model to more effectively leverage the characteristics of sinograms and achieve commendable restoration outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Spleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 109/L. Whether this association occurs in patients with thrombocytopenia is unclear. Pacritinib, a JAK2/IRAK1/ACVR1 inhibitor, demonstrated improved SVR versus best available therapy (BAT [best available therapy]; including ruxolitinib) in patients with myelofibrosis and platelet counts ≤ 100 × 109/L in the PERSIST‐2 study. Patients on study at the start of the 12‐week SVR window on pacritinib 200 mg twice daily or BAT were included. OS was evaluated among SVR responders versus non‐responders using different SVR thresholds (≥ 35%, ≥ 20%, ≥ 10%, and > 0%). Among patients on pacritinib (n = 89), SVR ≥ 10% demonstrated the greatest separation in OS curves between responders and non‐responders (HR, 0.00; 95% CI, 0.00–0.14; p < 0.01), though SVR ≥ 0% and SVR ≥ 20% were also associated with improved OS. No SVR threshold conferred OS benefit on BAT (n = 84), including ruxolitinib (n = 39). In patients with myelofibrosis and platelets ≤ 100 × 109/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR.Trial Registration: ClinicalTrials.gov number: NCT02055781 [ABSTRACT FROM AUTHOR]

Advanced breast cancer, as well as ineffective treatments leading to surviving cancer cells, can result in the dissemination of these malignant cells from the primary tumor to distant organs. Recent research has shown that microRNA 200c (miR‐200c) can hamper certain steps of the invasion–metastasis cascade. However, it is still unclear whether miR‐200c expression alone is sufficient to prevent breast cancer cells from metastasis formation. Hence, we performed a xenograft mouse experiment with inducible miR‐200c expression in MDA‐MB 231 cells. The ex vivo analysis of metastatic sites in a multitude of organs, including lung, liver, brain, and spleen, revealed a dramatically reduced metastatic burden in mice with miR‐200c‐expressing tumors. A fundamental prerequisite for metastasis formation is the motility of cancer cells and, therefore, their migration. Consequently, we analyzed the effect of miR‐200c on collective‐ and single‐cell migration in vitro, utilizing MDA‐MB 231 and MCF7 cell systems with genetically modified miR‐200c expression. Analysis of collective‐cell migration revealed confluence‐dependent motility of cells with altered miR‐200c expression. Additionally, scratch assays showed an enhanced predisposition of miR‐200c‐negative cells to leave cell clusters. The in‐between stage of collective‐ and single‐cell migration was validated using transwell assays, which showed reduced migration of miR‐200c‐positive cells. Finally, to measure migration at the single‐cell level, a novel assay on dumbbell‐shaped micropatterns was performed, which revealed that miR‐200c critically determines confined cell motility. All of these results demonstrate that sole expression of miR‐200c impedes metastasis formation in vivo and migration in vitro and highlights miR‐200c as a metastasis suppressor in breast cancer. [ABSTRACT FROM AUTHOR]

Abdominal systems such the liver, pancreas, spleen, and kidneys must be carefully dissected in order to properly diagnose and treat abdominal illnesses. Even while deep learning segmentation methods are excellent, there are still problems with many of them, including partial volume effects, image noise, and data asymmetry. The purpose of this research is to colourize CT scans in order to improve these segmentation techniques. For the purpose of segmenting various organs in thoracic CT images, we suggest an adversarial training technique for deep neural networks. U-Net-generative adversarial networks are the suggested adversarial network architecture. High quantities of GPU RAM are needed for this procedure (perhaps exceeding hardware restrictions) and training takes a long time. With the findings of this publication, By highlighting how great outcomes are still possible with a reduced-resource architecture, Our goal is to get more scientists interested in and involved with deep neural networks. We use cutting-edge pre-processing methods, multi-organ segmentation requires both a well-designed model with model fusion amongst models that have been trained on the same datasets. Using state-of-the-art approaches from a public competition as a benchmark, we show that our design is much better. [ABSTRACT FROM AUTHOR]

Background: Among various growth parameters, liver and spleen size is an important parameter used for the evaluation of patients with certain disorders and abnormalities in these organs. Aim: To determine the normal dimensions for the liver, spleen, and kidney in Egyptian infants, children, and adolescents from birth to 18 years. Methods: This cross-sectional randomized study was conducted on 1861 Egyptian infants, children, and adolescents from birth to 18 years for the establishment of Z score reference of liver, spleen, and kidney parameters. Results: Egyptian children of both sexes (51.5% boys and 48.5% girls) from birth to 18 years old were studied. Then Z scores reference for liver, spleen, and kidney parameters for both sexes were represented in detailed tables and graphs. There was no statistically significant difference between both sexes, so we used unisex tables and graphs (P > 0.05). Conclusions: Determination of pathologic changes in the size of the liver, spleen, and kidney necessitates knowing the normal range of dimensions for these organs. So, our study established a Z score chart for normal values of liver, spleen, and kidney size for children and adolescents from birth to 18 years. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Multi‐organ segmentation aids in disease diagnosis, treatment, and radiotherapy. The recently emerged photon counting detector‐based CT (PCCT) provides spectral information of the organs and the background tissue and may improve segmentation performance.We propose UNet‐based multi‐organ segmentation in PCCT using virtual monoenergetic images (VMI) to exploit spectral information effectively.The proposed method consists of the following steps: Noise reduction in bin‐wise images, image‐based material decomposition, generating VMIs, and deep learning‐based segmentation. VMIs are synthesized for various x‐ray energies using basis images. The UNet‐based networks (3D UNet, Swin UNETR) were used for segmentation, and dice similarity coefficients (DSC) and 3D visualization of the segmented result were evaluation indicators. We validated the proposed method for the liver, pancreas, and spleen segmentation using abdominal phantoms from 55 subjects for dual‐ and quad‐energy bins. We compared it to the conventional PCCT‐based segmentation, which uses only the (noise‐reduced) bin‐wise images. The experiments were conducted on two cases by adjusting the dose levels.The proposed method improved the training stability for most cases. With the proposed method, the average DSC for the three organs slightly increased from 0.933 to 0.95, and the standard deviation decreased from 0.066 to 0.047, for example, in the low dose case (using VMIs v.s. bin‐wise images from dual‐energy bins; 3D UNet).The proposed method using VMIs improves training stability for multi‐organ segmentation in PCCT, particularly when the number of energy bins is small. [ABSTRACT FROM AUTHOR]

Heat stress (HS) is one of the major economic problems facing the world's chicken industry. Besides decreased growth performance, HS reduces immune function in chickens. The principal part of the immunological function is the lymphatic organ. The spleen is a secondary lymphoid organ in birds. Sodium butyrate (SB) is the sodium salt of butyric acid and is suggested to be used to relieve heat stress. The current study aimed to evaluate the effect of sodium butyrate on the spleen in heat-stressed broilers. A total of 150 healthy broiler chicks (1 day old) were randomly divided into 4 groups: 1) control group fed on basal diet (BD) and normal temperature; 2) heat stress (HS) group (BD) and exposed to HS (34◦C for 8 h/day for 7 days starting from 29 days old); 3) low sodium butyrate group (BD + 0.5 g/kg SB every day and exposed to HS and 4) high sodium butyrate group (BD + 2 g/kg SB every day and exposed to HS. The spleen was harvested at the end of the experiments (36 days old). Our results revealed that HS caused severe damages, such as noticeable atrophy and loss of organization in the white pulp and hemorrhage in both white and red pulps. A low dose of SB supplementation showed full protection of the spleen tissue. However, the high dose might cause an adverse effect. In conclusion, SB especially low dose ameliorated the effect of heat stress. Therefore, we suggest using SB to face the heat stress in broilers, however with low doses. [ABSTRACT FROM AUTHOR]

Patients diagnosed with COVID-19 were seen to develop splenic infarction or abscess. This study aims to estimate the incidence of splenic infarction/abscess in COVID-19 patients and to examine the clinical and morphological changes in the infected spleen. In the splenectomy group, 63.5% of patients had an enlarged spleen measuring between 12.1 cm x 5.1 cm and 19.2 cm x 12.2 cm. The incidence of splenic infarction was 36.4%, while the incidence of splenic infarction complicated by abscess was 18.1%. The size of splenic infarcts varied from 3.1 cm x 1.4 cm to 10.2 cm x 4.3 cm. Splenic abscesses were present in 72.3% of patients. Of 596 patients with severe COVID-19, 12 had at least one splenic abscess (2.3%): three patients had multiple splenic abscesses, while the rest had a single abscess pocket. Splenic infarction was found in 116 patients (22.5%), including 6 patients who later developed splenic abscesses. [ABSTRACT FROM AUTHOR]

Introduction: Retinoblastoma (RB) is the most common paediatric intraocular malignancy. The Spleen Tyrosine Kinase (SYK) acts as a proto-oncogene crucial for RB cell survival and is absent in the normal retina, making it a valuable therapeutic target. Aim: Entospletinib, a selective oral SYK inhibitor currently in phase 2 trials for chronic lymphocytic leukaemia, was evaluated for its activity on the RB cell line Y-79. Materials and Methods: The effects of Entospletinib on cell proliferation and death of the human RB Y79 cells were assessed by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, phase contrast microscopy and AO/EtBr dual labeling. The Annexin-V kit was used to quantify the cell mortality following treatment using flow cytometry. The mRNA levels of caspase-3, BAX, BCL-2, SYK, p53, TNF-and NF-κB were measured using RT-PCR to better understand the mechanism of action of this drug. Western blot was used to further validate the data. Results: Entospletinib treatment led to a time- and dosedependent reduction in cell viability, with significant cytotoxicity observed at an IC50 of 61.3 μM/ml. Annexin V/Propidium Iodide (PI) staining demonstrated a dose-dependent increase in apoptosis. The treatment upregulated mRNA levels of Caspase-3, Bax, and p53 while downregulating SYK, TNF-α, and Bcl-2. RT-PCR and Western blot analyses confirmed a dose-dependent decrease in NF-κB/p65 expression. Conclusion: The study findings suggest that Entospletinib inhibits cell proliferation and induces apoptosis in RB cells by downregulating SYK/TNF-α/NF-κB/p65, highlighting its potential as a promising therapeutic candidate for RB. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic autoimmune disease with a long disease course and frequent relapse characteristics. It is now recognised to be associated with epidermal environments of inflammatory cytokines. However, its pathogenesis is still not completely clear. We found the haemorheology of psoriatic patients to be abnormal, and ageing and deformed erythrocytes increased in the blood. The abnormal erythrocytes were more likely to induce psoriasis, which was confirmed in a mouse model induced by different blood components of psoriatic patients/healthy volunteers. Spleen filtration dysfunction, which caused abnormal erythrocytes, was also more likely to induce psoriasis, which was confirmed in a mouse model induced by splenectomy. The mechanism was the weakening of the 'eat me' function of spleen macrophages phagocytizing ageing and deformed erythrocytes, resulting in the dysfunction of spleen filtration and the increase of ageing and deformed erythrocytes in the body. Additionally, the decreased oxygen‐carrying capacity and the declined antioxidant capacity of those erythrocytes led to the hypoxia environment, making psoriasis more likely to be induced. These findings demonstrate that spleen filtration dysfunction contributes to the pathogenesis of psoriasis and suggest that improving it may be an effective therapy for psoriasis and control its relapse. [ABSTRACT FROM AUTHOR]

Interleukin 27 (IL‐27) is a cytokine that regulates susceptibility to Leishmania infantum infection in humans and experimental models. This cytokine has not yet been described in canine leishmaniasis (CanL). Therefore, we investigated whether IL‐27 has a regulatory role in CanL. The EBI3 and p28 subunits of IL‐27 were measured in splenic leukocytes culture supernatant from dogs with CanL and compared to control dogs. We also correlated EBI3 and p28 levels with IL‐21, anti‐L. infantum antibodies and parasite loads. We performed functional assays followed by IL‐27 blockade and measured parasite loads, production of cytokines in splenic leukocytes culture supernatant, and the expression of PD‐1, CTLA‐4, phospho‐Stat‐1/3, T‐bet, GATA3 and nitric oxide production (NO). Both IL‐27 subunits increased in the supernatant of dogs with CanL compared to control dogs. EBI3 and p28 levels showed a moderate positive correlation with IL‐21 (r = 0.67, p < 0.0001 and r = 0.45, p < 0.012, respectively), and the EBI3 subunit was positively associated with anti‐L. infantum IgG antibodies (r = 0.38, p < 0.040) and parasite load (r = 0.47, p < 0.009). IL‐27 and IL‐21 participate of immune responses in CanL. IL‐27 may be associated with the failure of immunity to control parasite replication via upregulation of the expression of PD‐1, CTLA‐4, T‐bet and NO in splenic leukocytes from dogs with CanL. These findings suggest that the pathways regulated by IL‐27 are involved in CanL pathogenesis in the host, and may be targets for new therapies. [ABSTRACT FROM AUTHOR]

The spleen is a primary target of deoxynivalenol (DON) toxicity, but its underlying molecular mechanisms remain unclear. This study investigates the effects of DON on inflammation, splenic macrophage polarization, endoplasmic reticulum (ER) stress, and transcriptome changes (mRNA and lncRNAs) in mouse spleen. We found that DON exposure at doses of 2.5 or 5 mg/kg BW significantly induced inflammation and polarized splenic macrophages towards the M1 phenotype. Additionally, DON activated PERK-eIF2α-ATF4-mediated ER stress and upregulated apoptosis-related proteins (caspase-12, caspase-3). The ER stress inhibitor, 4-Phenylbutyric acid, significantly alleviated DON-induced ER stress, apoptosis, and the M1 polarization of splenic macrophages. Transcriptome analysis identified 1968 differentially expressed (DE) lncRNAs and 2664 DE mRNAs in mouse spleen following DON exposure. Functional enrichment analysis indicated that the upregulated genes were involved in pathways associated with immunity, including Th17 cell differentiation, TNF signaling, and IL-17 signaling, while downregulated mRNAs were linked to cell survival and growth pathways. Furthermore, 370 DE lncRNAs were predicted to target 255 DE target genes associated with immune processes, including the innate immune response, interferon-beta response, cytokine production regulation, leukocyte apoptosis, and NF-κB signaling genes. This study provides new insights into the mechanisms underlying DON toxicity and its effects on the immune system. [ABSTRACT FROM AUTHOR]

Recurrent problems of patients with myelofibrosis (MF) are cytopenias, debiliating disease-related symptoms and splenomegaly. Whereas the latter are usually addressed by the JAK1/2 inhibitors ruxolitinib and fedratinib, cytopenias often remain critical. Momelotinib, a JAK1/2 inhibitor recently approved for the treatment of anemic MF patients, was shown to improve anemia via a direct inhibition of activin A receptor type I. In this German-wide, multicenter, retrospective analysis the safety and efficacy profile of momelotinib was evaluated in a real world setting within a cohort of 60 MF patients independent of pre-treatment. The median duration of treatment was 12 weeks. As a new, but manageable safety finding, creatinine increase (CTC°1–2) was detected in 10/60 patients (17%). Interestingly, not only hemoglobin levels increased in 84% of patients, but also platelet values (67%). In the cohort of transfusion-dependent individuals (n = 38), transfusion requirement improved in 15 patients (39%) with 8 reaching transfusion independency (21%). Transfusion independency was achieved within a median of 4 weeks (range 2–12). Spleen size decreased in 13/53 individuals (25%) with a median response time of 6 weeks. Thereof, 11 patients had been pre-treated with JAK inhibitor(s) (85%). Clinical improvement was detected in 24/51 symptomatic individuals (47%) with a median response time of 4 weeks. 5 patients stopped treatment due to side effects (8%), 6 patients due to a worsening of clinical symptoms (10%). Taken together, the MoReLife analysis identifies momelotinib as potent and safe therapeutic option also for heavily pre-treated cytopenic MF patients under real world conditions. [ABSTRACT FROM AUTHOR]

Background: Liver and splenic stiffness measurements (LSM and SSM) are useful to predict varices and clinical decompensation in cirrhosis. SSM values are highly variable and overlapping and no guidelines exists on what constitutes normal SSM, that might limit interpretation of results. Methods: Consecutive subjects with LSM < 6 kPa and reliable SSM (FibroScan630 Expert device with spleen-dedicated module) and no vascular liver disease were analysed for significant correlations of SSM values with age, sex, BMI, portal and splenic vein diameter, splenic diameter, liver fat and diabetes. Based on timeline of SSM, subjects were randomly assigned in 70:30 ratio into derivation [n = 502] and validation subset [n = 214]. Results: Of 7200 subjects with simultaneous reliable LSM and SSM, 715 fulfilled the selection criteria (mean age: 43.8 ± 12.8 years, 67.2% male, mean BMI-26.4 ± 4.5 kg/m2). The mean SSM was 22.6 ± 5.8 kPa (c10–c90 percentile range: 15.2–31.3 kPa) and followed the normal distribution curve. In the derivation subset, mean SSM for males was higher than female (23.06 ± 6.2 vs. 21.78 ± 5.93 kPa; p = 0.028). SSM value correlated with LSM (r = 0.454, p = 0.001). Mean SSM in subjects with LSM 3–4, 4.1–5 and 5.1–6 kPa were 21.7 ± 5.8, 22.27 ± 5.67 and 23.76 ± 5.88 kPa (p value = 0.001). There was no difference in SSM based on age, BMI, diabetes and liver fat on ultrasound. Above results hold true for subjects in validation subset. Conclusion: SSM range in subjects with normal LSM and no vascular liver disease using spleen-dedicated module varies from 15.2 to 31.3 kPa, values being higher in male and not affected by Age, BMI, spleen size, liver fat and diabetes. Our results may serve as reference point in evaluation of SSM in compensated advanced liver disease patients. [ABSTRACT FROM AUTHOR]

Background: The traditional herbal medicine Atractylodes macrocephala Koidz. (A. macrocephala) is commonly utilized for alleviating symptoms associated with spleen deficiency, abdominal distension, diarrhea, and constipation. These pharmacological effects are attributed to a variety of active constituents. However, the specific bioactive compounds responsible for promoting defecation and gastrointestinal transit in A. macrocephala remain unidentified. Methods: The primary polysaccharide characteristics of PAMK was elucidated by HPLC, FT‐IR, and HGPGC. Efficacy of PAMK (0.07, 0.14, and 0.28 mg/g) on mice was evaluated in a spleen deficiency constipation mouse model by analyzing stool parameters, constipation‐related physiological indexes, and SCFAs. The expression levels of 5‐HT3R, 5‐HT4R, and related receptor genes were examined by RT‐qPCR, and neurotransmitters were examined using ELISA. Finally, the diversity of gut microbiota was analyzed with 16S rDNA sequencing. Key Results: The results showed that PAMK significantly reduced the gastrointestinal transport time and increased the number of fecal pellets and fecal water content in spleen deficiency constipation model mice. PAMK kept the balance of 5‐HT, SCFAs, TPH‐1, SERT, CgA, and neurotransmitter levels (VIP, SP, MTL) in mice colon. In addition, PAMK could regulate the abundance of gut microbiota such as Alistopes, Bacteroides, and Odoribacter in spleen deficiency constipation model mice gut. Conclusions and Inferences: It can be concluded that PAMK effectively ameliorated the symptoms of spleen deficiency constipation in mice by modulating the expression of 5‐HT and its associated receptors. The underlying mechanism was elucidated, providing a solid theoretical foundation for the therapeutic application of A. macrocephala in treating spleen deficiency constipation and offering potential for developing novel approaches to address this condition. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, diabetic and obese patients experienced higher rates of hospital admissions, severe illness, and mortality. However, vaccinations failed to provide those vulnerable populations the same level of protection against COVID-19 severity as those without diabetic and obese phenotypes. Our study aimed to investigate how diabetes mellitus (DM) impacts the immune response following vaccination including the artificially designed trimeric SARS-CoV-2 spike (S)-protein. By using two diabetic mouse models, ob/ob mice (obese, hyperglycemic, and insulin-resistant) and STZ-treated mice (insulin-deficient and hyperglycemic), we observed a significant reduction in S-protein-specific IgG antibody titer post-vaccination in both diabetic models compared to wild-type (WT) mice. Both diabetic mouse models exhibited significant abnormalities in spleen tissue, including marked reductions in splenic weight and the size of the white pulp regions. Furthermore, the splenic T-cell and B-cell zones were notably diminished, suggesting an underlying immune dysfunction that could contribute to impaired antibody production. Notably, vaccination with the S-protein, when paired with an optimal adjuvant, did not exacerbate diabetic cardiomyopathy, blood glucose levels, or liver function, providing reassurance about the vaccine′s safety. These findings offer valuable insights into potential mechanisms responsible for the decreased persistence of antibody production in diabetic patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer immunotherapy has evolved rapidly in the last decade. A newly emerging immunotherapeutic approach utilizes oncolytic viruses to enhance the ability of the body's own immune system to recognize and clear tumor cells. We have recently developed a novel chimeric oncolytic virus and demonstrated its anti-tumoral effects in various preclinical mouse models. To gain mechanistic insights into the immune response to this form of therapy at the cellular level and to identify targets to potentially further improve the therapy, we analyzed the immune cell signature in the tumors, blood, and lymphoid tissue in a syngeneic melanoma mouse model by flow cytometry. Both local and systemic immune responses were observed. Furthermore, selective depletion of cytotoxic T cells indicated that these cells are the main players in mediating the therapeutic response to this novel virotherapy. Background/Objectives: Oncolytic virotherapy is a promising approach in cancer immunotherapy. We have previously described a recombinant hybrid oncolytic virus (OV), VSV-NDV, which has a favorable safety profile and therapeutic immunogenicity, leading to direct oncolysis, abscopal effects, and prolonged survival in syngeneic in vivo tumor models. While OVs are known to mediate systemic anti-tumor immune responses, the detailed characterization of local and systemic immune responses to fusogenic oncolytic virotherapy remains unexplored. Methods and Results: We analyzed immune cell compartments in the spleen, blood, tumor-draining lymph nodes (TDLNs), and tumors over the course of VSV-NDV therapy in a bilateral syngeneic melanoma mouse model. Our results revealed significant local infiltration and activation of T lymphocytes in tumors and globally in the blood and spleen. Notably, in vivo CD8+ T cell depletion led to complete abrogation of the tumor response, highlighting the crucial role of T cells in promoting the therapeutic effects of oncolytic VSV-NDV. In vitro co-culture experiments enabled the interrogation of human immune cell responses to VSV-NDV-mediated oncolysis. Human peripheral blood mononuclear cells (PBMCs) were efficiently stimulated by exposure to VSV-NDV-infected cancer cells, which recapitulates the in vivo murine findings. Conclusions: Taken together, these data characterize a broad anti-tumor immune cell response to oncolytic VSV-NDV therapy and suggest that CD8+ T cells play a decisive role in therapeutic outcome, which supports the further development of this chimeric vector as a multimechanistic immunotherapy for solid cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with relapsed, refractory, or metastatic osteosarcoma have few therapeutic options. Our findings demonstrated the efficacy of a DC vaccine generated using CD103+ cDC1 cells and OS cell lysates against the primary tumor and lung metastases, as well as its ability to induce a systemic immune response. This cDCV therapy elicited an increase in the infiltration of CD8+ T-cells into the primary and metastatic tumors as well as the TdLNs. cDCV efficacy was increased when combined with anti-CTLA-4. The failure of immunotherapies has been linked to their inability to induce infiltration of T-cells into the tumor. Therefore, our data suggest the potential for this novel immunotherapy using innate immune cells (type 1 CD103+ dendritic cells) alone or in combination with checkpoint blockade for patients with relapsed or metastatic OS, a tumor type that is refractory to the majority of current immunotherapies. Background: We generated a CD103+DC vaccine using K7M3 OS cell lysates (cDCV) and investigated its ability to induce regression of primary tumors, established lung metastases, and a systemic immune response. Methods: A bilateral tumor model was used to assess cDCV therapy efficacy and systemic immunity induction. K7M3 cells were injected into mice bilaterally. Right-sided tumors received PBS (control) or cDCV. Left-sided tumors were untreated. Tumor growth was compared between the vaccine-treated and untreated tumor on the contralateral side and compared to the control group. The immune cell profiles of the tumors, and tumor-draining lymph nodes (TdLNs) and spleen were evaluated. To determine the efficacy of systemic cDCV therapy against established lung metastases, K7M3 cells were injected intratibially. Leg amputation was performed 5 weeks later. Mice were treated intravenously with PBS or cDCV and euthanized 6 weeks later. Lungs, TdLNs and spleen were collected. The number and size of the lung nodules were quantified. The immune cell profile of tumor, and lymph nodes and spleen were also evaluated. Using this same model, we evaluated the effect of cDCV + anti-CTLA-4. Results: cDCV therapy inhibited the treated and untreated tumors and increased the number of T-cells in these tumors and the lymph nodes compared to control-treated mice. Systemic cDCV therapy administered following amputation decreased the size and number of lung metastases, and increased T-cell numbers in the tumor and lymph nodes. Combining anti-CTLA-4 with cDCV therapy increased cDCV efficacy against lung metastases. Conclusions: Intratumor cDCV generated a systemic immune response inhibiting the growth of both the treated and untreated tumors, with increased T-cells in the tumor and lymph nodes. Systemic cDCV was effective against established lung metastases. Efficacy was increased by anti-CTLA4. cDCVs may provide a novel therapeutic approach for relapsed/metastatic OS patients. [ABSTRACT FROM AUTHOR]

Purpose: C‐reactive protein (CRP) functions as a nonspecific marker in various inflammatory disorders, particularly in evaluating the efficacy of pharmacological treatments in patients with ulcerative colitis. The existing body of evidence does not offer adequate support for the direct implication of CRP in modulating the advancement of ulcerative colitis. Methods: Our study employed a rigorous mouse model. An ulcerative colitis mouse model was established by subjecting CRP‐deficient mice to dextran sulfate sodium (DSS) treatment. The phenotype of the mice, which encompassed parameters such as body weight, colon length, and spleen weight, was meticulously evaluated. Additionally, various physiological and biochemical indicators were assessed, including colon histopathology, expression levels of inflammatory factors, and staining of the intestinal mucus layer. Results: The absence of CRP did not significantly affect the phenotype, physiological characteristics, and biochemical indices in a mouse model of ulcerative colitis compared to mice with wild‐type CRP. Additionally, eliminating intestinal bacteria flora interference through antibiotic treatment revealed that mice lacking CRP did not demonstrate any notable variations in the ulcerative colitis model. Meanwhile, the survival rate of mice lacking CRP did not exhibit a statistically significant difference compared to wild‐type mice. Conclusion: The results of our study suggest that CRP may not directly mediate ulcerative colitis. Instead, it is more likely to be a bystander that is present alongside with elevated inflammatory factors. Further investigation is warranted to determine the precise role of CRP in humans, given the significant limitations associated with the use of mouse models. [ABSTRACT FROM AUTHOR]

Hyperammonemia (HA) can induce oxidative and nitrosative stress in peripheral organs, potentially exacerbating Hepatic Encephalopathy (HE). This study assessed the efficacy of Andrographis paniculata aqueous extract (APAE) in mitigating oxidative and nitrosative stress caused by non-cirrhotic HA in rat livers, spleens, and kidneys. HA was induced via intraperitoneal injection of ammonium acetate, while APAE was administered orally. The study measured malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and glutathione reductase (GR) to gauge oxidative stress, and nitric oxide (NO) levels as a marker of nitrosative stress. Both acute and chronic HA altered the levels of antioxidant enzymes, MDA, and NO in the organs studied. APAE treatment helped restore SOD, catalase, and GR levels, and decreased MDA and NO levels, demonstrating its potential in reducing oxidative stress linked to HA in the liver, spleen, and kidney. [ABSTRACT FROM AUTHOR]

For the first time, an analysis of leukocyte changes in the organs of the immune system (pronephros, mesonephros, and spleen) of the Baikal omul Coregonus migratorius (Georgi, 1775) (Salmoniformes: Coregonidae) infected with Dibothriocephalus dendriticus (Nitsch, 1824) (syn. Diphyllobothrium dendriticum) (Cestoda: Diphyllobothriidea) is presented in natural habitat conditions. In the pronephros of infected fish, the number of poorly differentiated neutrophils (myelocytes and metamyelocytes) was significantly higher than in uninfected fish, which indicated inflammatory processes. D. dendriticus triggered the immunoregulatory processes in the body of infected fish, as evidenced by the decrease in the total number of lymphocytes and prolymphocytes (B-lymphocytes) in the pronephros and the increase in prolymphocytes in the spleen. The other effector elements (cells of the monocyte–macrophage lineage, basophils, and eosinophils) were barely involved in antiparasitic defense. [ABSTRACT FROM AUTHOR]

Introduction: Haemoperitoneum due to spontaneous splenic rupture is a rare condition. Methods: We present a case of AL-type amyloidosis and chronic kidney disease (CKD) who is presented with diffuse abdominal pain. A contrast-enhanced CT scan of the abdomen revealed moderate to large amounts of free fluid in the peritoneum, indicating splenic rupture causing haemoperitoneum. Result: The patient underwent emergency exploratory laparotomy and splenectomy. After the operation, the patient was closely monitored in the ICU and was transferred to the ward on postoperative day 3. He was discharged home on day 6. Conclusion: This case report highlights a rare occurrence of haemoperitoneum secondary to spontaneous splenic rupture in a patient with AL amyloidosis. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Edulis Fungi is the property of Acta Edulis Fungi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)