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Pancreaticoduodenectomy (PD) with combined portal vein resection sometimes causes left-sided portal hypertension, which can be a problem. An appropriate treatment strategy for hemorrhagic ectopic varices due to left-sided portal hypertension after PD has not yet been determined. We report a case of repeated variceal rupture around the pancreatojejunostomy site. A 65-year-old woman with a history of PD for pancreatic head cancer was admitted with a chief complaint of bloody stools. She was diagnosed with pancreatojejunostomy variceal rupture, and an endoscopic cyanoacrylate injection was performed. As rebleeding occurred 2 weeks after the first treatment, endoscopic cyanoacrylate injection was repeated, and hemostasis was achieved. Additionally, she had esophageal, colonic, and gastrojejunostomy varices, and the future risk of these variceal ruptures was considered very high. Hence, a splenectomy was performed to prevent rebleeding or other variceal ruptures. Endoscopic cyanoacrylate injection is a useful treatment for hemorrhagic varices around the pancreatojejunostomy site. It is also necessary to understand portal vein hemodynamics and provide appropriate additional treatment in cases of recurrent variceal rupture due to left-sided portal hypertension after PD.

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Introdução: A angina bolhosa hemorrágica (ABH) é uma condição rara caracterizada pelo surgimento súbito de bolhas de sangue nas mucosas orais e orofaringe. Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características clínicas, etiológicas e histopatológicas da angina bolhosa hemorrágica, além de abordar métodos de diagnóstico e opções de tratamento. Materiais e métodos: Foi realizada uma busca por artigos científicos publicados de 2010 a 2023, nas bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e ScienceDirect. Foram coletados artigos em inglês e português utilizando as palavras-chave "angina bolhosa hemorrágica", "estomatite bolhosa hemorrágica benigna", "hemorrhagic bullous angina" e "benign hemorrhagic bullous stomatitis". Conclusão: A ABH é escassamente documentada na literatura, com muitos dados ausentes ou subnotificados. Embora seja uma condição benigna com rápida evolução espontânea, o procedimento diagnóstico deve ser rigoroso para descartar outras possíveis lesões.

Introduction: Bullous hemorrhagic angina (ABH) is a rare condition characterized by the sudden appearance of blood blisters on the oral mucosa and oropharynx. Objective: This work aims to provide a comprehensive analysis of the clinical, etiological and histopathological characteristics of hemorrhagic bullous angina, in addition to addressing diagnostic methods and treatment options. Materials and methods: A search was carried out for scientific articles published between 2010 and 2023, in the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and ScienceDirect databases. Articles were found in English and Portuguese using the keywords "hemorrhagic bullous angina", "benign herrhagic bullous stomatitis", "hemorrhagic bullous angina" and "benign herrhagic bullous stomatitis". Conclusion: ABH is scarcely documented in the literature, with many data missing or underreported. Although it is a benign condition with rapid spontaneous evolution, the diagnostic procedure must be rigorous to rule out other possible lesions.

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Poststroke aphasia hinders patients' emotional processing and social adaptation. This study estimated the risks of depression and related symptoms in patients developing or not developing aphasia after various types of stroke. Using data from the US Collaborative Network within the TriNetX Diamond Network, we conducted a retrospective cohort study of adults experiencing their first stroke between 2013 and 2022. Diagnoses were confirmed using corresponding International Classification of Diseases, Tenth Revision, Clinical Modification codes. Patients were stratified by poststroke aphasia status and stroke type, with propensity score matching performed to control for confounders. The primary outcome was depression within one year post-stroke; secondary outcomes included anxiety, fatigue, agitation, emotional impact, and insomnia. Each matched group comprised 12,333 patients. The risk of depression was significantly higher in patients with poststroke aphasia (hazard ratio: 1.728; 95% CI 1.464-2.038; p < 0.001), especially those with post-hemorrhagic-stroke aphasia (hazard ratio: 2.321; 95% CI 1.814-2.970; p < 0.001). Patients with poststroke aphasia also had higher risks of fatigue, agitation, and emotional impact. Anxiety and insomnia risks were higher in those with post-hemorrhagic-stroke aphasia. Poststroke aphasia, particularly post-hemorrhagic-stroke aphasia, may increase the risks of depression and associated symptoms, indicating the need for comprehensive psychiatric assessments.

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Intracerebral hemorrhage is a lethal cerebrovascular disease, and the inevitable secondary brain injury (SBI) is responsible for serious disability and death. Perfect therapeutic goal is to minimize SBI and restore neurobehavioral functions. Recently, neuroprotection is highlighted to reduce SBI, but it still faces "Neuronal survival but impaired functions" dilemma. Herein, this work further proposes a novel combinational therapeutic strategy of neuroprotection and neurogenesis toward this goal. However, appropriate therapeutic agents are rarely reported, and their discovery and development are urgently needed. Selenium participates in various physiological/pathological processes, which is hypothesized as a potential targeting molecule. To explore this effect, this work formulates an ultra-small selenium nanodot with a seleno-amino acid derived carbon dot domain and a hydrophilic PEG layer, surprisingly finding that it increases various selenoproteins levels at perihematomal region, to not only exert multiple neuroprotective roles at acute phase but promote neurogenesis and inhibit glial scar formation at recovery phase. At a safe dose, this combinational strategy effectively prevents SBI and recovers neurobehavioral functions to a normal level. Furthermore, its molecular mechanisms are revealed to broaden application scopes in other complex diseases.

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BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS), a life-threatening zoonosis caused by hantavirus, poses significant mortality risks and lacks specific treatments. This study aimed to delineate the transcriptomic alterations during the recovery phases of HFRS. METHODS: RNA sequencing was employed to analyze the transcriptomic alterations in peripheral blood mononuclear cells from HFRS patients across the oliguric phase (OP), diuretic phase (DP), and convalescent phase (CP). Twelve differentially expressed genes (DEGs) were validated using quantitative real-time PCR in larger sample sets. RESULTS: Our analysis revealed pronounced transcriptomic differences between DP and OP, with 38 DEGs showing consistent expression changes across all three phases. Notably, immune checkpoint genes like CD83 and NR4A1 demonstrated a monotonic increase, in contrast to a monotonic decrease observed in antiviral and immunomodulatory genes, including IFI27 and RNASE2. Furthermore, this research elucidates a sustained attenuation of immune responses across three phases, alongside an upregulation of pathways related to tissue repair and regeneration. CONCLUSION: Our research reveals the transcriptomic shifts during the recovery phases of HFRS, illuminating key genes and pathways that may serve as biomarkers for disease progression and recovery.

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MicroRNAs (miR) are a group of small, non-coding RNAs of 17-25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection-two genotypes (GI.1 and GI.2)-in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1ß, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1ß was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection-two genotypes (GI.1 and GI.2)-and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen).

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Leptospirosis is a globally distributed zoonosis with multisystemic involvement in canine species, capable of causing a pulmonary hemorrhagic syndrome (LPHS) in the most severe cases. In humans, the neutrophil to lymphocyte ratio (NLR), platelets to lymphocytes (PLR) and systemic immune-inflammation index (SII) have been described as predictors of morbidity and mortality in various pathologies, but no such studies have been developed for canine leptospirosis. Hence, we aimed to assess the usefulness of NLR, PLR and SII in dogs affected with leptospirosis, focusing on those that died or survived after hospitalization, whether or not they developed LPHS. The leptospirosis group was composed by 36 dogs while the control group consisted of 32 healthy dogs. The NLR, associated with inflammation, demonstrated a threefold or greater increase in all leptospirosis groups compared to the control group (median 2.44 ± 1.66) (developing or not LPHS). Dogs that died (median 67.78 ± 158.67), developed LHPS (median 85.17 ± 143.77), or both developed LHPS and died (median 67.78 ± 155,14) had a lower PLR in comparison to the control group (median 101,82 ± 53,75) and the rest of groups, but no statistically significant differences were observed (p > 0.05). The SII was higher in leptospirosis-affected dogs that survived (median 1356,92 ± 2726,29) and statistically significant differences were observed in those who did not develop LPHS (median 1770,41 ± 2630,77; p < 0.05) compared to the control group (median 555,21 ± 313,26). Our data shows that NLR may be used as inflammation indicator, while more studies are needed for PLR and SII in canine leptospirosis.

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The research aimed to examine the impact of coated cysteamine (CS) and choline chloride (CC) on relieving the pathological effects of fatty liver hemorrhagic syndrome (FLHS) in laying hens. FLHS was induced by a high-energy low-protein (HELP) diet. Ninety laying hens were equally divided into 5 treatments with 6 replicates per treatment (3 hens/replicate). The control treatment (Cont) was fed a basal diet, while the remaining treatments were fed a HELP diet. Under the HELP dietary plan, 4 treatments were set by a 2 × 2 factorial design. Two levels of CS (CS-: 0.00 mg/kg CS; CS+: 100 mg/kg diet) and 2 levels of choline (CC-: 1,182 mg/kg; CC+: 4,124 mg/kg) were set and named CS-CC- (HELP), CS+CC-, CS-CC+ and CS+CC+. The liver of the CS-CC- (HELP) group became yellowish-brown and greasy, with hemorrhages and bleeding spots. Elevated (P < 0.05) plasma and hepatic ALT and AST and hepatic MDA levels, combined with reduced (P < 0.05) plasma and hepatic SOD and GSH-Px activities in the CS-CC- (HELP) group proved that FLHS was successfully induced. Dietary supplementation of CS, CC, or both (CS+CC+) in HELP diets relieved the pathological changes, significantly (P < 0.05) reduced the AST and ALT levels, and strengthened the antioxidant potential in laying hens under FLHS. The highest (P < 0.001) plasma adiponectin concentration was observed in the CS+CC- and lowest in the CS-CC- (HELP) group. In addition, CS and CC supplementation lowers the elevated levels of hepatic T-CHO and TG by increasing the HDL-C and reducing LDL-C levels (P < 0.05) than CS-CC- (HELP) group. CS supplementation, either alone or with CC, helps laying hens restore their egg production. It could be stated that CS and CC supplements could ameliorate the adverse effects of FLHS by regulating antioxidant enzymes activities, modulating the hepatic lipid metabolism, and restoring the production performance in laying hens. Hence, adding CS and CC could be an effective way to reduce FLHS in laying hens.

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OBJECTIVE: To determine the effect of tranexamic acid (TXA) on clot hyperfibrinolysis (HF), defined as excessive clot lysis at 30 minutes (LY30%), with rapid thromboelastography (rTEG) or rTEG samples spiked with tissue plasminogen activator (tPA-stressed rTEG), in dogs with hemorrhagic shock. METHODS: Prospective blinded clinical trial at 2 teaching hospitals, March 16, 2018, to May 20, 2022. Twenty-five dogs with hemorrhagic shock and HF were treated with standard care plus either TXA (20 mg/kg; TXA group) or saline (SAL group) over 20 minutes followed by an infusion of the same dose over 8 hours. Rapid TEG and tPA-stressed rTEG assays were performed immediately before study drug administration and at 8, 12, and 24 hours afterwards (T0, T8, T12, and T24, respectively). RESULTS: 4 dogs died or were euthanized before the end of the study period due to disease/injury severity. All survivors had normal rTEG LY30% values after T0; the value for 1 nonsurvivor increased at T8. The tPA-stressed LY30% normalized in all TXA (n = 14) and 8 of 11 SAL dogs at T8; TXA dogs had lower median tPA-stressed rTEG LY30% values at T8 and T12 than SAL dogs (P = .001 and .02, respectively). There was no treatment effect on blood product administration or survival, and no adverse effects were attributed to TXA administration. CONCLUSIONS: Resuscitation with or without TXA reduced HF identified by tPA-stressed rTEG. Hyperfibrinolysis was completely suppressed at the conclusion of the 8-hour TXA infusion. CLINICAL RELEVANCE: Although TXA treatment stopped HF, there was no effect on survival or transfusion requirements.

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Both ischemic and hemorrhagic strokes are critical health issues and the incidence is on the rise. The rapid neurological degeneration that can occur with either type of stroke warrants prompt medical attention. In the article, we critically reviewed the literature examining their incidence, pathophysiology, and present treatment strategies. Clinical trials show conflicting findings, with ischemic strokes accounting for 87% of all strokes. Brain injury following an ischemic stroke results in cell death and necrosis, immune cells being the primary actors in the process of neuroinflammation. In order to develop neuroprotective drugs against ischemic stroke, detailed investigation of glutamate production and metabolism as well as downstream pathways controlled by glutamate receptors provides significant information on the underlying mechanisms. The permeability of the blood-brain barrier and the degradation of glutamine synthase are two potential mechanisms by which peritoneal dialysis accelerates brain-to-blood glutamate clearance and thus reduces glutamate levels in the brain after a stroke. Oxidative stress in an ischemic stroke disturbs the oxidant-antioxidant balance, which is particularly problematic for brain cells that are high in polyunsaturated fatty acids. Because of demographic factors like age, sex, race/ethnicity, and socioeconomic status, the incidence and prevalence of stroke differ across people and regions. For rapid diagnosis and treatment decisions, diagnostic imaging tools such as vascular imaging, CT, and MRI are essential. To aid in the recovery and lessen neurological impairments following a stroke, novel avenues of research are under investigation on neuroprotective medications that target inflammation, oxidative stress, and neuronal death.

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Background: Mixed venous saturation (SvO2) is considered the gold standard to assess the adequacy of tissue oxygen delivery (DO2) in shock states. However, SvO2 monitoring is challenging as it requires an invasive catheter and frequent blood sampling. Non-invasive methods, including near-infrared spectroscopy, have demonstrated low sensitivity to tissue dysoxia. Methods: We fabricated a new device that uses resonance Raman spectroscopy (RRS) to quantify oxyhemoglobin saturation (ShbO2) in the esophagus (eShbO2), tongue (tShbO2), and liver (hShbO2). In two rat models of hemorrhagic shock, we quantified (1) The correlation of RRS-measured ShbO2 to SvO2 during progressive hemorrhage (n=20) and (2) The value of these metrics to predict near-term mortality in fixed, severe hemorrhage (mean blood pressure =25 mm Hg; n=18). Results: In model 1, eShbO2 (r=0.705, p<0.0001) and tShbO2 (r=0.724, p<0.0001) correlated well with SvO2 and with serum lactic acid (eShbO2-lactate r=0.708, p<0.0001; tShbO2-lactate r=0.830, p<0.0001). hShbO2 correlated poorly with both SvO2 and lactic acid. Using time-matched ShbO2-SvO2 pairs, the performance of ShbO2 to detect severe tissue hypoxia (SvO2<20%) was excellent (AUC 0.843 for eShbO2, 0.879 for tShbO2). In model 2, eShbO2 showed a maximized threshold of 40% with 83% of animals dying within 45 minutes of this cut-off, demonstrating accuracy as a monitoring device. This was similar for tShbO2, with a threshold of 50%, predicting death within 45 minutes in 76% of animals. ShbO2 showed superior sensitivity to invasive monitoring parameters, including MABP<30 mm Hg (sensitivity 59%), pulse pressure<15 mm Hg (sensitivity 50%), and heart rate>220 bpm (sensitivity 39%, p=0.004). Conclusions: eShbO2 represents a new paradigm to assess the adequacy of DO2 to a tissue. It constitutes a promising monitoring method to evaluate tissue oxygen saturation in real time and non-invasively, correlating with SvO2 and time to death. Level of evidence: Level III, therapeutic/care management.

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Objective: Benign phonotraumatic lesions of the vocal folds (BVFLs) are typically seen in younger female patients with high vocal loads. Hemorrhagic polyps (HPs) do not fit the classic paradigm of most BVFLs, as they tend to occur in an older population, have a male predominance, and report to result from a vocal accident. We present one of the largest cohorts of HPs, to reexamine their etiology and clinical features. Methods: Retrospective cohort study, inclusive of all patients with HP managed by the senior authors between the years 2016 through 2023. Demographic data, management, phonotraumatic risk factors, pre- and post-treatment VHI-10 were reviewed. We examined patient videostroboscopy, categorized the size of the lesion, and identified any concurrent mucosal abnormality. Results: One hundred and eleven patients had confirmed HP, 84 males (75.7%). Thirty-five patients were size category 1; pinpoint (28.9%), 57 were category 2; less than 1/3rd the vocal fold (45.5%), and 26 were category 3; greater than 1/3rd the vocal fold (21.5%). Ten patients (9%) had bilateral HPs. Thirty-five patients had an additional 40 mucosal lesions in addition to the HP(s). The onset of symptoms was gradual in 60% of patients. The mean pretreatment VHI-10 was 18.0 (SD 10.7), compared to 6.0 (SD 10.5) post-treatment, (p < .001). 57/111 patients reported high voice demand professions or recreational activities. The average self-reported talkative scale score was 7.6/10. Patients were managed with operative microdirect laryngoscopy and microflap excision (53.1%), in-office clinic potassium titanyl phosphate (KTP) laser (24.3%), voice therapy alone (7.2%), and KTP in the operating room (6.3%). Conclusions: In our cohort, most patients were male, had high vocal demands, reported gradual symptom onset, and almost a third of patients had additional BVFLs. Level of evidence: Level 3: Retrospective cohort study.

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Acute hemorrhagic leukoencephalitis (AHLE), also known as Weston-Hurst syndrome or Hurst disease, is a rare and rapidly progressive form of acute disseminated encephalomyelitis. It is characterized by severe inflammation, hemorrhage, and necrosis within the white matter of the brain. AHLE often follows an upper respiratory infection or other systemic illnesses, suggesting a potential post-infectious autoimmune mechanism. The disease is associated with a high mortality rate and significant disability among survivors. We present the case of a 46-year-old Indian woman with a history of chronic hepatitis B (HBV) who presented with an insidious onset of right-sided limb weakness and bi-frontal headaches. Initial brain MRIs showed features of tumefactive demyelination. Despite aggressive treatment with intravenous (IV) methylprednisolone, IV immunoglobulin, and anti-edema measures, the patient's condition rapidly deteriorated, leading to a diagnosis of AHLE following the emergence of hemorrhagic white matter lesions on repeat MRI. Remarkably, with continued treatment, the patient survived and showed gradual neurological improvement, although she remained significantly debilitated at the time of discharge. AHLE represents one of the most severe forms of demyelinating diseases, often resulting in rapid neurological decline and high mortality. This case highlights the potential link between chronic HBV infection with a high viral load and the onset of AHLE. The patient's recovery underscores the importance of early recognition and aggressive treatment in improving outcomes, even in conditions with traditionally poor prognosis. Clinicians should maintain a high index of suspicion for AHLE in patients with chronic viral infections presenting with neurological symptoms. Prompt and aggressive management can be life-saving, and ongoing research is needed to better understand the pathogenesis and optimal treatment strategies for this rare but devastating condition.

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Background: Crimean-Congo hemorrhagic fever (CCHF) is a major emerging infectious disease threat, and children are reported to have a milder disease course compared with adults, in contrast to other viral hemorrhagic fevers. The aim of this study was to compare adult and pediatric patients with CCHF to improve understanding of pathogenesis and the natural history of the disease. Materials and Methods: A retrospective analysis of all children and adults admitted with confirmed CCHF between 2011 and 2020. Epidemiological, clinical, and laboratory features were collated on proformas, together with clinical management details. The Severity Grading Score (SGS) system was used to stratify mortality risk. Data from children were compared with adults in the same center and with other published pediatric cohort studies. Results: A total of 47 children with a median (ranges) age of 14 (2-17) years and 176 adults with a median (ranges) age of 52 (18-83) years with confirmed CCHF were included. The most frequent symptoms in adults were fever, muscle-joint pain, headache, nausea, and vomiting; the most frequent in children were fever, anorexia, nausea, vomiting, and abdominal pain. Adults had lower lymphocyte and platelet counts and higher liver transaminase and creatinine levels than children. SGS values were lower in children, but 97.9% children received ribavirin compared with 8.5% of adults (p < 0.001), and they had associated longer median lengths of hospital admission (10 vs. 7 days, p < 0.001). Mortality of 1 out of 47 (2.1%) children was similar to 11 other cohorts reported in Türkiye and lower than 13.1% in adults (23/176) in the same center (p = 0.059). Conclusions: Children have lower CCHF-related mortality, less severe disease, and different clinical syndromes at presentation. The majority of published case definitions for screening for CCHF in the main endemic countries do not differentiate between adults and children and omit four of the five most common presenting features in children.

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BACKGROUND: Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, the clinical therapies aimed at BBB protection after IVT remain limited. METHODS: One hundred patients with AIS who underwent IVT were enrolled (42 with HT and 58 without HT 24 h after IVT). Based on the cytokine chip, the serum levels of several AIS-related proteins, including LCN2, ferritin, matrix metalloproteinase-3, vascular endothelial-derived growth factor, and X-linked inhibitor of apoptosis, were detected upon admission, and their associations with HT were analyzed. After finding that LCN2 was related to HT in patients with IVT, we clarified whether the modulation of LCN2 influenced BBB dysfunction and HT after thrombolysis and investigated the potential mechanism. RESULTS: In patients with AIS following IVT, logistic regression analysis showed that baseline serum LCN2 (p = 0.023) and ferritin (p = 0.046) levels were independently associated with HT. A positive correlation between serum LCN2 and ferritin levels was identified in patients with HT. In experimental studies, recombinant LCN2 (rLCN2) significantly aggravated BBB dysfunction and HT in the thromboembolic stroke rats after thrombolysis, whereas LCN2 inhibition by ZINC006440089 exerted opposite effects. Further mechanistic studies showed that, LCN2 promoted endothelial cell ferroptosis, accompanied by the induction of high mobility group box 1 (HMGB1) and the inhibition of nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Ferroptosis inhibitor ferrostatin-1 (fer-1) significantly restricted the LCN2-mediated BBB disruption. Transfection of LCN2 and HMGB1 siRNA inhibited the endothelial cell ferroptosis, and this effects was reversed by Nrf2 siRNA. CONCLUSION: LCN2 aggravated BBB disruption after thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway, this may provide a promising therapeutic target for the prevention of HT after IVT.

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Fatty liver hemorrhagic syndrome is the main cause of noninfectious death of laying hens and results in substantial economic losses to the poultry industry. This study focused on evaluating the effects of Poly-dihydromyricetin-fused zinc nanoparticles (PDMY-Zn NPs) on antioxidant capacity, liver lipid metabolism, and intestinal health in laying hens. A total of 288 Jingfen laying hens (52 wk old) with similar body weights were randomly divided into 4 dietary groups with 6 replicates in each group for 8 wk. The control group received a basal diet, while the treatment groups were supplemented with PDMY-Zn NPs at levels of 200, 400, and 600 mg/kg, respectively. The results indicate that PDMY-Zn NPs supplementation can enhance antioxidant parameters (P < 0.05) in the blood and liver of laying hens. Simultaneously, it can mitigate vacuolar degeneration and inflammatory necrosis in hepatocytes, improve the relative expression level of related parameters associated with liver lipid metabolism and key regulatory genes (P < 0.05). Furthermore, it has been observed to reshape the composition and diversity of cecum microbes by increasing beneficial probiotics such as Lactobacillus and Prevotella, while also enhancing villi height and villi/crypt ratio in the duodenum and ileum (P < 0.05). Additionally, it elevates liver bile acid content along with the relative expression of key genes involved in liver synthesis (P < 0.05). In summary, PDMY-Zn NPs showed potential to alleviate fatty liver hemorrhagic syndrome by enhancing antioxidant capacity, regulating liver lipid metabolism, and maintaining intestinal health.

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Background and Aims: Crimean-Congo Hemorrhagic Fever (CCHF) is a significant public health concern transmitted by ticks. This study seeks to thoroughly grasp the epidemiology and transmission patterns of CCHF, which is caused by the CCHF virus (CCHFV), a member of the Nairovirus genus in the Bunyaviridae family. Methods: The study investigates the global distribution and endemicity of CCHF, its mortality rates, modes of transmission (including tick bites, contact with infected animal blood, and limited person-to-person transmission), and factors influencing its prevalence across different regions. Genetic diversity within CCHFV and its impact on transmission dynamics are explored, along with efforts to control the disease through tick prevention, antiviral treatment, and the development of vaccines and diagnostics. Results: CCHFV exhibits widespread distribution, particularly in the Middle East, Africa, Asia, and Eastern Europe, with an overall mortality rate of approximately 30% and a case fatality rate ranging from 10% to 40%. Transmission occurs primarily through tick bites and contact with infected animal blood, with limited person-to-person transmission. Livestock workers, slaughterhouse employees, and animal herders in endemic areas are most affected by their frequent interaction with sick animals and ticks. Genetic diversity within CCHFV contributes to variations in transmission dynamics, complicating control efforts. Antiviral ribavirin shows efficacy in treating CCHF infection. Conclusion: This study underscores the importance of further research to understand the enzootic environment, transmission routes, and genetic diversity of CCHFV for effective control measures, including the development of vaccines, treatment options, and diagnostics.

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Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonosis caused by a Nairovirus, Crimean-Congo hemorrhagic fever virus (CCHFV). Despite its wide geographical distribution, the epidemiology of CCHF in northern Africa is incompletely understood and its occurrence in Algeria is virtually unknown. The present survey aimed to determine the prevalence of CCHF antibodies and to identify the potential risk factors associated with CCHFV seropositivity among the one-humped camel (Camelus dromedarius) in southern Algeria. A total of 269 camels selected randomly from slaughterhouses in three wilayas were employed in the study. Sera sampled were tested for the presence of CCHFV-specific IgG antibodies using enzyme-linked immunosorbent assay (ELISA). CCHFV seropositivity was recorded in 255 out of 269 camels accounting for a prevalence rate of 94.8% (95%CI = 92.14-97.45). The seroprevalence by origin was determined to be 97% (193/199) in imported camels and 86% (49/57) in local ones (p > 0.25). Tick presence (OR = 12.35, 95%CI = 1.41-107.43, p < 0.05) was recorded as the only potential risk factor for contracting CCHFV. This study shows for the first time that camels are exposed to CCHFV in Algeria with a significantly high seroprevalence. It also underlines the need for further research to investigate the broader extent of circulating CCHFV in the country, whether in humans, animals, or ticks.

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Prime editing (PE) is a recently developed genome-editing technique that enables versatile editing. Despite its flexibility and potential, applying PE in human induced pluripotent stem cells (hiPSCs) has not been extensively addressed. Genetic disease models using patient-derived hiPSCs have been used to study mechanisms and drug efficacy. However, genetic differences between patient and control cells have been attributed to the inaccuracy of the disease model, highlighting the significance of isogenic hiPSC models. Hereditary hemorrhagic telangiectasia 1 (HHT1) is a genetic disorder caused by an autosomal dominant mutation in endoglin (ENG). Although previous HHT models using mice and HUVEC have been used, these models did not sufficiently elucidate the relationship between the genotype and disease phenotype in HHT, demanding more clinically relevant models that reflect human genetics. Therefore, in this study, we used PE to propose a method for establishing an isogenic hiPSC line. Clinically reported target mutation in ENG was selected, and a strategy for PE was designed. After cloning the ENGineered PE guide RNA, hiPSCs were nucleofected along with PEmax and hMLH1dn plasmids. As a result, hiPSC clones with the intended mutation were obtained, which showed no changes in pluripotency or genetic integrity. Furthermore, introducing the ENG mutation increased the expression of proangiogenic markers during endothelial organoid differentiation. Consequently, our results suggest the potential of PE as a toolkit for establishing isogenic lines, enabling disease modeling based on hiPSC-derived disease-related cells or organoids. This approach is expected to stimulate mechanistic and therapeutic studies on genetic diseases.a.

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BACKGROUND: To assess the long-term outcome of large brain arteriovenous malformations (AVMs) (volume > 10 ml) underwent combined embolization and stereotactic radiosurgery (E+SRS) versus SRS alone. METHODS: Patients were recruited from a nationwide multicenter prospective collaboration registry (MATCH study, August 2011-August 2021) and categorized into E+SRS and SRS alone cohorts. Propensity score-matched survival analysis was employed to control for potential confounding variables. The primary outcome was a composite event of non-fatal hemorrhagic stroke or death. Secondary outcomes were favorable patient outcomes, AVM obliteration, favorable neurological outcomes, seizure, worsened mRS score, radiation-induced changes (RIC), and embolization complications. Furthermore, the efficacy of distinct embolization strategies was evaluated. Hazard ratios (HRs) were computed utilizing Cox proportional hazard models. RESULTS: Among 1063 AVMs who underwent SRS with or without prior embolization, 176 patients met the enrollment criteria. Following propensity score matching, the final analysis encompassed 98 patients (49 pairs). Median (interquartile range) follow-up duration for primary outcomes spanned 5.4 (2.7-8.4) years. Overall, the E+SRS strategy demonstrated a trend toward reduced incidence of primary outcomes compared to the SRS alone strategy (1.44 vs 2.37 per 100 patient-years; HR, 0.58 [95 % CI, 0.17-1.93]). Regardless of embolization degree or strategy, stratified analyses further consistently revealed a similar trend, albeit without achieving statistical significance. Secondary outcomes generally exhibited equivalence, but the combined approach showed potential superiority in most measures. CONCLUSIONS: This study suggests a trend toward lower long-term non-fatal hemorrhagic stroke or death risks with the E+SRS strategy when compared to SRS alone in large AVMs (volume > 10 ml).