Acute Stage Research Articles

Antiepileptic and antioxidant effects of aqueous extract of Lippia multiflora Moldenke (Verbenaceae) on pilocarpine-induced seizures in Mus musculus Swiss mice

Epilepsy is a chronic neurological disorder that affects the central nervous system. Approximately 3% of the population at some point in their lives would be affected by epileptic disorders in the world, that is to say nearly 70 million people and therefore about 85% live in developing countries. The objective of this study is to determine the anticonvulsant effects of Lippia multiflora on the animal model of epileptogenesis induced by pilocarpine injection in mice during the acute phase. Mice were treated with different doses of the aqueous extract of L. multiflora or sodium valproate. The anticonvulsant effects were evaluated 24 after the injection of pilocarpine by referring to the Racine scale. Then a daily treatment was done for one week corresponding to the acute stage of the disease. Oxidative stress parameters were measured from brain samples taken on the last day of treatment. The injection of pilocarpine induced the Status epilepticus, which is translated by the appearance of convulsive seizures while the administration of different doses of the aqueous extract of L. multiflora led to a significant decrease of the seizures induced by pilocarpine in mice. In addition, L. multiflora extract restored endogenous levels of oxidative stress markers (MDA and NO) and increased the activity of oxidative stress enzymes (SOD, CAT and GSH). L. multiflora possesses anticonvulsant properties mediated by the involvement of GABAA receptors and antioxidants.

Психологическая помощь лицам в стадии острой травмы (на материале работы с жертвами террористического акта в «Крокус Сити Холле»)

<p>The paper presents a description of methods and techniques for providing psychological assistance to people in the acute stage of trauma, using specific cases of psychological counseling of clients in the days following a terrorist attack at Crocus City Hall as an example. The main research objectives were to identify characteristic signs of acute trauma and propose possible ways to provide psychological support for adults, children, and adolescents. The article analyzes domestic and international literature on the psychological consequences of terrorist attacks, considering the main mental disorders and symptoms associated with the trauma of being a witness, as well as methods and techniques for working with individuals who have experienced mental trauma. Five specific cases of people seeking psychological help are described in the article. Based on personal experience, the authors suggest a possible algorithm for dealing with trauma in witnesses and describe some effective techniques: eye movement desensitization and reprocessing (EMDR), breathing exercises, and imagotherapeutic techniques using a metaphor (“Resource (safe) place”, as well as techniques aimed at muscle relaxation and self-regulation.</p>

Biomarkers of inflammation and neoangiogenesis in premature rupture of membranes

BACKGROUND: Premature rupture of membranes complicates up to 2–10% of full-term pregnancies and up to 40% of all premature pregnancies. It is believed that the main cause of premature rupture of membranes is inflammation caused by both infectious agents and autoimmune processes. Numerous studies are aimed at searching for biomarkers that can predict inflammation in premature rupture of membranes. AIM: The aim of this study was to determine the levels of pro-inflammatory cytokines such as interleukin-6, -18 and procalcitonin, as well as interferon-α and soluble endoglin, in the blood serum of pregnant women with premature rupture of membranes and women in labor with timely discharge of amniotic fluid and evaluate the possibility of using these parameters to optimize obstetric tactics. MATERIALS AND METHODS: This study included 69 patients delivered at the Clinic of Obstetrics and Gynecology of the Academician I.P. Pavlov First Saint Petersburg State Medical University from January 2022 to March 2023. The main study group consisted of 53 pregnant women with premature rupture of membranes, the control group included 16 women with term labor and timely discharge of amniotic fluid, or amniotomy performed in the first stage of labor. The levels of interleukin-6, -18, interferon-α, procalcitonin and soluble endoglin in maternal peripheral blood were assessed using enzyme-linked immunosorbent assay. Pregnancies complicated by severe preeclampsia, placenta abruption and chronic maternal diseases in the acute stage were excluded from the study. RESULTS: At the time of rupture, the minimum gestational age was 33+0 weeks and the maximum age — 41+3 weeks. The median duration of the anhydrous interval was 31.8 hours. No significant differences in interleukin-6, -18, procalcitonin and soluble endoglin concentrations were revealed in the main and control groups, interferon-α level being higher in the comparison group. The median concentration of interferon-α in pregnant women with premature rupture of membranes was 1.64 pg/ml and in women with timely discharge of amniotic fluid — 4.61 pg/ml (p = 0.001). A weak direct correlation was revealed between soluble endoglin and interleukin-18 concentrations (R = 0.26; p = 0.03), as well as a moderate direct correlation between soluble endoglin and procalcitonin levels (R = 0.4; p 0.001). CONCLUSIONS: The study did not reveal differences in the concentrations of interleukin-6, -18, procalcitonin and soluble endoglin in the comparison groups. A decrease in interferon-α level in the blood in pregnant women increases the risk of developing premature rupture of membranes. The correlations between soluble endoglin and interleukin-18 or procalcitonin concentrations may indicate an association between different mechanisms of the pathogenesis of premature rupture of membranes. In this regard, an integrated approach and analysis of a combination of several cellular bioregulators are eligible to predict infectious complications in premature rupture of membranes.

Acute kidney injury in lamotrigine-induced DRESS syndrome.

We present a case of lamotrigine-triggered DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome with acute kidney injury stage 3. A 17-year-old girl with known epilepsy treated with lamotrigine presented with acute kidney injury as well as skin eruption, fever, and apathy. Extended diagnostics, considering infectious and autoimmune diseases, remained unremarkable. Lamotrigine blood levels were within the target range. Kidney biopsy showed acute interstitial nephritis with tubular necrosis. Methylprednisolone pulse therapy led to an improvement in kidney function; skin eruption and neurological symptoms resolved. During the hospital stay, the girl admitted to inconsistent and variable intake of lamotrigine, occasionally resulting in notable overdosing. This report demonstrates that acute kidney injury in lamotrigine-induced DRESS syndrome is an acute interstitial nephritis with tubular necrosis, an aspect that has not been deeply characterized so far. Additionally, we aim to elevate awareness towards non-adherence as cause of disease, especially among the adolescent population.

Cardiovascular magnetic resonance 3D LGE imaging for atrial fibrillation ablation

Abstract Objective To assess feasibility and reliability of cardiac magnetic resonance (CMR) imaging in visualizing left atrial (LA) structural changes that patients with paroxysmal atrial fibrillation (PAF) undergo acutely and long-term post ablation. Two different ablation methods i.e pulsed filed ablation (PFA) and cryoablation were studied. Background Pulmonary vein (PV) isolation has become the cornerstone technique for catheter ablation in patients with drug-refractory atrial fibrillation (AF). At present, almost all ablation technologies are mediated by a thermal effect. Recently, pulsed field ablation (PFA) has been introduced as a new energy source. PFA is a non-thermal ablative modality in which high voltage ultra-short pulses are applied to target tissue, while preserving the extracellular matrix architecture, nerves, and microvascular structures. Few data exist showing different structural LA changes between the two methods using Three-Dimensional (3D) Late Gadolinium Enhancement (LGE) Imaging. Methods CMR imaging was performed pre-ablation, acutely (<24 h), and 3 months post-ablation in 10 patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation with PFA (n = 5) or cryoablation (n = 5). 3D LGE and T2-weighted images were analysed. We obtained two data sets of 3D whole heart LGE imaging with high resolution, 20minutes post gadolinium injection. Patients underwent two acquisitions: the conventional respiratory navigated, electrocardiographically-gated 3D fast gradient echo (1.3slice thickness, 256x256 matrix acquisition) and the image-navigated isotropic high resolution 3D LGE with Dixon water-fat separation. 3D LGE data were analysed using a dedicated (ADAS LA) software in order to produce a 3D-LA model visualization of LGE areas. Results In the acute stage, LGE volume was 50% larger after PFA vs. cryoablation (P < 0.001), and oedema on T2 imaging was significantly smaller (visual estimation) on PFA cases. LGE rings surrounding PV ostia were more homogeneous after PFA, with no sign of microvascular damage or intramural hemorrhage as compared to cryoablation cases. In the chronic stage, the majority of acute LGE had disappeared after PFA, whereas most LGE persisted after cryo-ablation. The two 3D LGE sequences used for analysis showed complete agreement in the visualization of atrial scar with superior image quality of the novel sequence. The mean acquisition time for 3D LGE imaging was 11±4minutes for the conventional fast gradient echo sequence, and 5±2minutes for the novel 3D self-image navigated LGE sequence. Conclusions CMR imaging may help in visualization and understanding of LA structural remodeling post different ablation techniques.

Effect of 4-Week Pulmonary Rehabilitation on Dyspnea, Fatigue, Quality of Life and Radiological Findings in a Patient with Pulmonary Renal Syndrome Suffering from Pneumonia - A Case Study

Background: Pulmonary renal syndrome (PRS) is a rare, autoimmune disease, defined as combination of pulmonary symptoms (cough, chest pain and dyspnea- at acute stage) and rapidly progressive glomerulonephritis. Pneumonia is an inflammatory condition caused by infectious agents leading to fever, cough and shortness of breath. We report a case of a 42 years old female suffering from PRS and recently diagnosed with bacterial pneumonia. Medically she was managed through antibacterial and oral corticosteroids. At initial encounter of pneumonia, she was in intensive care unit and had cough, dyspnea, pyrexia and fatigue with oxygen saturation (SpO2) of 94% on 15 liters of oxygen via non rebreathable mask. Her chest x-ray demonstrated lobar pneumonia involving right upper lobe. Even after the resolution of pneumonia, she had fatigue, dyspnea and baseline SpO2 of 90-92% on room air. Thus, all the above traits were treated by pulmonary rehabilitation. Purpose: To study the effect of tailor-made pulmonary rehabilitation in pneumonia along with PRS. Method: Physiotherapy was divided into 2 phases: (1) Acute phase: chest physiotherapy (breathing exercises, nebulization, bronchial hygiene, percussion and vibration) (2) Subacute and Late phase: dyspnea management, energy conservation techniques, early mobilization, exercise training (aerobic and strength) Result: 4 weeks of pulmonary rehabilitation resulted in significant improvement in radiological finding, St. George’s respiratory questionnaire (85.39 to 15.53), SpO2 at room air (90% to 99%), Modified Medical Research council score (4 to 1), fatigue severity scale (43 to 21) with an improved inspiratory capacity measured by incentive spirometer. Conclusion: Pulmonary rehabilitation is a structured and multifaceted approach which improves respiratory function, enhance physical fitness, reduces fatigue and the length of hospital stay, prevent recurrence and optimize overall quality of life. Our findings underscore the pivotal role of pulmonary rehabilitation in the treatment of pneumonia alongside Pulmonary Renal Syndrome. Keywords: pulmonary rehabilitation, pneumonia, pulmonary renal syndrome

#2343 Fabry disease screening in patients with chronic kidney disease and dialysis at a single medical center in Taiwan

Abstract Background and Aims Chronic Kidney Disease (CKD) poses a significant global health challenge, with diverse contributing factors impacting its progression. Among these, Fabry Disease, a rare lysosomal storage disorder, has emerged as a potential complicating factor. Despite its relevance, the prevalence of Fabry Disease among CKD patients, particularly in Taiwan, remains insufficiently explored. Recognizing and understanding the occurrence of Fabry Disease in CKD populations are crucial for comprehensive patient care and may have implications for treatment strategies. Additionally, investigating the relationship between kidney function and Plasma α-Gal A activity is essential. α-Gal A, the enzyme deficient in Fabry Disease, may experience altered activity levels in the presence of compromised kidney function. Clarifying this connection is pivotal for gaining insights into the intricate interplay between Fabry Disease and CKD. This study aims to achieve three key objectives (1) Determine Fabry Disease Prevalence among CKD Patients in Taiwan.(2) Investigate the Impact of Kidney Function on Plasma α-Gal A Activity.(3) Characterize Gene Mutation Patterns and Demographic Data of Fabry Patients in CKD Population in Taiwan: Method Fabry Disease assessment involved a two-stage process, tailored to the patient's gender. Males underwent a dry blood test measuring α-galactosidase activity; samples below 15% of the adult average were deemed positive. Females were screened based on lyso-Gb3 levels in whole blood; a result exceeding 0.8 ng/ml was considered positive. Positive screenings prompted genomic DNA extraction, and the GLA gene's seven exons and intron 4 segment ([GRCh38/Hg38] chrX:101,399,610-101,399,874) were PCR-amplified. Sanger sequencing identified pathogenic variants. This gender-specific, multi-step approach ensures precision. Defined thresholds and advanced genomic techniques enhance diagnostic accuracy. The method provides a robust means of identifying Fabry Disease, supporting early intervention and personalized treatment. Results Study Recruitment: Initially, 2000 subjects enrolled, but 155 withdrew, yielding a final cohort of 1845 patients for analysis. Screening and Referral: Among 1602 subjects, 26 males (1.6%) were referred for DBS LysoGB3 check-up due to low serum α-Gal A activity. In a cohort of 243 females, 6 individuals (2.4%) underwent GLA genetic sequencing due to elevated lyso-GB3 levels. Clinical Presentation - Male Case: A male with acute stroke symptoms and CKD stage 3b (eGFR 34.5 mL/min/1.73 m²) showed significantly low DBS α-Gal A activity (0.48 μmol/hr) and elevated Plasma LysoGB3 (28.08 ng/ml).GLA genetic sequencing revealed a specific deletion (c.1072-1074delGAG, p. (Glu358 del)) in exon 7, leading to a Fabry disease diagnosis, classifying it as a specific type. The family pedigrees of this male patient are visually represented in Fig. 1, illustrating the genetic relationships within the family. Clinical Presentation - Female Case: A female on hemodialysis for four years, cause unknown, exhibited a DBS LysoGB3 level of 0.5 ng/ml. GLA genetic sequencing identified a nucleotide variation (c.640-801G>A) in intron 4, establishing a diagnosis of Fabry disease with the cardiac variant (301500). Fig. 2 demonstrates the relationship between serum DBS GLA activity and different stages of CKD. Our analysis reveals that in CKD stages 1, 2, 3 (3a and 3b), and 4, the serum GLA activity is significantly higher compared to stage 5. Conclusion The prevalence of Fabry Disease in our cohort was 0.1% (2 out of 1845 individuals), featuring one female with the cardiac variant and one male with the class type. Our investigation unveiled a significant rise in serum GLA activity in CKD stages 1–4 compared to stage 5, suggesting potential implications for early CKD detection. Moreover, serum α-Gal A activity displayed a notable correlation with age, BUN, and eGFR across CKD stages 1–5, questioning its status as a biomarker for advanced CKD and aging in CKD patients. This prompts consideration for a large-scale study to validate this hypothesis.

#2561 Association of acute kidney injury stage with in-hospital mortality in elderly patients with hip fractures

Abstract Background and Aims Elderly individuals often experience hip fractures and acute kidney injury (AKI), both of which are associated with higher rates of morbidity and mortality. This study aimed to evaluate whether the severity of AKI is associated with higher mortality rates in elderly patients with hip fractures. Method Patients aged 65 years and older, who underwent surgery for hip fracture between October 2015 and October 2020, were retrospectively evaluated. Those with known chronic kidney disease stages 4, 5, or end-stage kidney disease were excluded. AKI was defined and categorized into stages 1, 2, and 3 according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Results In the study, 780 elderly patients with hip fractures were included, with a median age of 82.0 years (interquartile range 77.0–87.0) and 22.4% of them being men. Of these, 172 patients (22.1%) experienced AKI, with 125 (72.7%), 26 (15.1%), and 21 (12.2%) of these patients categorized as having stage 1, 2, and 3 AKI, respectively. Higher AKI stages were independently associated with increased in-hospital mortality compared to patients without AKI (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.18–6.55, P=0.940 for AKI stage 1; OR 14.09, 95% CI 1.47–135.52, P=0.022 for AKI stage 2; and OR 413.79, 95% CI 45.84–3735.28, P<0.001 for AKI stage 3). Furthermore, compared to patients without AKI, those with AKI stage 3 had a significantly increased risk of mortality (hazard ratio 15.30, 95% CI 2.65–88.48, P=0.002). Conclusion A higher stage of AKI is independently associated with increased in-hospital mortality in elderly patients with hip fractures. Prevention and prompt treatment of AKI, especially higher AKI stages, is important in elderly patients with hip fractures.

#1914 Comprehensive single-cell sequencing and lipidomics identify diverse injury states and cholesterol dynamics of the PTs in AKI-to-CKD transition

Abstract Background and Aims The underlying cellular events and metabolic dysfunction of acute kidney injury (AKI) transformed to chronic kidney disease (CKD) is still largely unclear. Previous studies have suggested lipids and metabolites have a profound impact on acute and chronic inflammation. One of the main sites of renal lipid accumulation is the proximal tubule cells (PTs). Here we demonstrated the injury states and cholesterol dynamics of PTs and its potential function in AKI to CKD in unilateral ischemia-reperfusion injury (UIR) mice model. Method We employed single-cell combinatorial indexing lipidomics to analyze 15 mouse kidneys from a mouse model of failed repaired UIR at five time points. We identified cell types through unsupervised clustering analysis. Differential gene expression, enrichment analysis and main function scoring were applied to define functional heterogeneity and injury states of PTs. Next, pseudotime analysis of differentiation transitions was performed to create the diverse PT lineages. Finally, using SCENIC analysis, we identified the key transcription factors that drive the differentiation of PTs. Results We identified 13 main cell clusters and the dynamic changes in the process of AKI to CKD transition were analysed. A remarkable decrease in PTs after injury at day 1 followed with a recovery at day 3 post AKI were observed. Spatiotemporal profiling of the main cell types showed that the most injured areas in the acute stages of kidney injury are primarily concentrated in the outer stripe, specifically the region where the proximal straight tubules (PSTs) are located. In order to gain a higher resolution of the dynamics of PST subtypes during AKI to CKD, we performed sub-clustering analysis specifically on PSTs, partitioning them into 10 subclusters. Single-cell analysis identified maladaptive PSTs (PST-5) with the highest apoptosis and ferroptosis scores. Notably, pseudotime analysis revealed that PST-5 differentiated from PST-4, which has the highest lipid metabolism score. Indeed, among all the cells in the kidney, the PTs exhibited the most active metabolic reprogramming due to their differentiation and redifferentiation early after AKI. Lipid omics profiling reveals an abnormal elevation of the cholesterol metabolites 27-hydroxycholesterol (27-OH) and 25-hydroxycholesterol (25-OH) following AKI. Interestingly, the PST-4-specific expression of Cyp7b1 served as a key enzyme regulating the concentration of 27-OH. This gene has been found to be significantly absent after AKI. Moreover, the binding of 27HC, a natural ligand, to endogenous estrogen receptor alpha (ERα) leads to the upregulation of heme oxygenase 1 (Hmox1), thereby promoting ferroptosis. Finally, SCENIC analysis revealed that Cyp7b1-mediated accumulation of 27-HC is dependent on the transcription factor Atf3. Conclusion Our results indicate that Cyp7b1 deficiency confers ferroptosis, which are primarily dependent on the upregulation of cellular cholesterol homeostasis and 27-HC secretion, leading to the progression of AKI. These findings suggest that the Cyp7b1/Hmox1/Atf3/27-HC axis may serve as a potential therapeutic target for preventing the development of CKD.

Left ventricular function assessment in Kawasaki disease by two-dimensional global longitudinal systolic strain with automated function imaging.

Kawasaki disease is an acute febrile vasculitis of childhood mainly affecting children under 4 years of age. In the acute stage of the disease, heart function decreases and gradually returns to normal after treatment. However, subendocardial involvement may persist, which cannot be assessed by M-mode echocardiography. Strain echocardiography is a recently developed technique to assess subendocardial involvement of myocardial deformation. We aimed to study the stratified strain of left ventricular function in a Kawasaki patient at least 6 months after the acute stage of the disease with special conditions for entering the study using two-dimensional speckle-tracking imaging. Between September 2020 and October 2022, 27 healthy children and 27 children with a history of Kawasaki disease more than 6 months ago were evaluated using two-dimensional global longitudinal peak systolic strain with automated function imaging technology. The mean age of patients was 5.6 years. With M-mode echocardiography, ejection fraction of each group was in the normal range. Mean (± standard deviation) global longitudinal peak strain in four-chamber view of girls with Kawasaki disease was - 23.74 ± 2.77, and that in boys with Kawasaki disease was - 20.93 ± 2.06 (P value = 0.008). GLPS (global longitudinal peak strain) was compared as an overall average and as in a separate segment, which showed significant difference in two comparisons. In our study, a decrease in the function of some cardiac segments is reported. Global longitudinal peak strain in four-chamber view was significantly lower in boys. Comparing different segments, a difference in global left ventricular long-axis strain was found between the two groups. On the other hand, there was a major difference between the two groups in the basal inferolateral, basal anterolateral, and mid-inferolateral, which receives blood from Left Circumflex artery. Using stain echocardiography to detect continued subendocardial involvement in asymptomatic children with a history of Kawasaki disease for a better understanding of the condition, effective management and follow-up is recommended.

Detection frequency and duration of circulating antiphospholipid syndrome markers in patients with verified COVID-19

Aim: to develop enzyme-linked immunosorbent tests for assessing the antiphospholipid syndrome (APS) markers and determine prevalence of three antiphospholipid antibody (aPL) types at different COVID-19 stages. Materials and Methods. A comparative longitudinal controlled study was conducted by examining 120 subjects with COVID-19 diagnosis verified by reverse transcription polymerase chain reaction. Donor serum samples collected before November 2019 were used as a control group. The laboratory study included measurement of IgA, IgM and IgG against β2-glycoprotein 1 (β2-GP1), cardiolipin, phosphatidylserine-prothrombin complex (PS-PT) by using domestically produced test systems based on indirect two-step enzyme-linked immunosorbent assay. Results. Validation of the developed experimental tests was carried out in comparison with foreign commercial analogues in accordance with international standards. Alternative antigenic targets for effective diagnosis of antibodies against β2-GP1 were studied. Analyzing rate of aPL in patients at different COVID-19 stages showed that in acute vs. convalescence stage it was higher by 1.3-fold (81.7 and 65.0 %, respectively). The first rank detection place was assigned to IgG against β2-GP1, cardiolipin and PS-PT, the second – IgM against cardiolipin. The profile of the detected antibodies changed at various COVID-19 stages driven by time frame elapsed from the moment of diagnosis. Conclusion. Recombinant constructs are created and analytical conditions are optimized for determining various aPL types. It was shown that along with other viral infections, COVID-19 triggers autoantibody production demonstrating that 54.2 % individuals infected with SARS-CoV-2 were positive at least for one autoantibody type. The majority of such virus-associated aPL are presumably transiently positive.

REPEATED MYOCARDIAL INFARCTIONS ASSOCIATED WITH KAWASAKI SYNDROME

Kawasaki syndrome is characterized by damage to the coronary arteries with the formation of aneurysms, which persist and progress after the completion of the acute stage of the process and cause hemodynamically significant stenoses and thrombosis. The literature research data on cardiac pathology in patients with Kawasaki syndrome are presented. A clinical case of a young non-mongoloid patient with a high probability of Kawasaki syndrome suffered in childhood is described. Repeated myocardial infarctions, multiple aneurysms of characteristic shapes and sizes in the coronary arteries are confirmation of this disease. With the development of coronary pathology in young people, when conducting a diagnostic search, it is necessary to remember about the Kawasaki syndrome.

Therapeutic potential of stem cells in subarachnoid hemorrhage

Abstract Aneurysm rupture can result in subarachnoid hemorrhage, a condition with potentially severe consequences, such as disability and death. In the acute stage, early brain injury manifests as intracranial pressure elevation, global cerebral ischemia, acute hydrocephalus, and direct blood–brain contact due to aneurysm rupture. This may subsequently cause delayed cerebral infarction, often with cerebral vasospasm, significantly affecting patient outcomes. Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes. Investigating the mechanisms of subarachnoid hemorrhage- induced brain injury is paramount for identifying effective treatments. Stem cell therapy, with its multipotent differentiation capacity and anti-inflammatory effects, has emerged as a promising approach for treating previously deemed incurable conditions. This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

MicroRNA-451 Regulates Angiogenesis in Intracerebral Hemorrhage by Targeting Macrophage Migration Inhibitory Factor.

Intracerebral hemorrhage (ICH) is a subtype of stroke with the highest fatality and disability rate. Up to now, commonly used first-line therapies have limited value in improving prognosis. Angiogenesis is essential to neurological recovery after ICH. Recent studies have shown that microRNA-451(miR-451) plays an important role in angiogenesis by regulating the function of vascular endothelial cells. We found miR-451 was significantly decreased in the peripheral blood of ICH patients in the acute stage. Based on the clinical findings, we conducted this study to investigate the potential regulatory effect of miR-451 on angiogenesis after ICH. The expression of miR-451 in ICH mouse model and in a hemin toxicity model of human brain microvascular endothelial cells (hBMECs) was decreased the same as in ICH patients. MiR-451 negatively regulated the proliferation, migration, and tube formation of hBMECs in vitro. MiR-451 negatively regulated the microvessel density in the perihematoma tissue and affected neural functional recovery of ICH mouse model. Knockdown of miR-451 could recovered tight junction and protect the integrity of blood-brain barrier after ICH. Based on bioinformatic programs, macrophage migration inhibitory factor (MIF) was predicted to be the target gene and identified to be regulated by miR-451 inhibiting the protein translation. And p-AKT and p-ERK were verified to be downstream of MIF in angiogenesis. These results all suggest that miR-451 will be a potential target for regulating angiogenesis in ICH.

Lipidome is a valuable tool for the severity prediction of coronavirus disease 2019.

To describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19. This case-control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids. Totally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19. Lipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.

Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China

Study objectiveThe use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DesignA retrospective cohort study. SettingThis study was conducted at one tertiary care hospital in China. PatientsWe evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). InterventionsEligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MeasurementsThe primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. Main resultsAfter matching, hydroxyethyl starch use [8.5 (IQR: 7.5–10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74–1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75–1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41–0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95–1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. ConclusionsHydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.

Crosstalk between human immunodeficiency virus infection and salivary bacterial function in men who have sex with men.

Engaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual's positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect. Based on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200-499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM. The core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts. As HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.

Presence of Self-Reported Sleep Alterations After Stroke and Their Relationship With Disability: A Longitudinal Study.

Sleep disorders have a prevalence of 30% to 70% in post-stroke individuals. The presence of sleep disorders and poor sleep quality after stroke can affect important functions and lead to worse outcomes. However, most studies are restricted to the acute post-stroke stage only. To investigate the frequency of self-reported sleep alterations in a sample of chronic stroke individuals and to identify which self-reported sleep alterations were associated with disability. Prospective exploratory study. Self-reported sleep alterations were measured by the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, and STOP-Bang Questionnaire. The dependent variable was measured 3 years after the first contact by the Modified Rankin Scale (mRS). Step-wise multiple linear regression analysis was employed to identify which sleep alterations were associated with disability. Sixty-five individuals with stroke participated. About 67.7% of participants had poor sleep quality, 52.4% reported insomnia symptoms, 33.9% reported excessive daytime sleepiness, and 80.0% were classified as intermediate or high risk for obstructive sleep apnea. Only risk for obstructive sleep apnea was significantly associated with disability and explained 5% of the variance in the mRS scores. Self-reported sleep alterations had a considerable frequency in a sample of chronic stroke individuals. The risk of obstructive sleep apnea was associated with disability in the chronic stage of stroke. Sleep alterations must be considered and evaluated in the rehabilitation process even after a long period since the stroke onset.

The clinical characteristics of neutrophil extracellular trap in patients with severe cerebral venous sinus thrombosis and its prognostic value in acute and subacute patients

Objective: To explore the clinical characteristics of neutrophil extracellular trap (NET) in patients with severe cerebral venous sinus thrombosis (CVST) and to study their prognostic value in the acute and subacute phases. Methods: This study is a retrospective case series analysis. Clinical and pathological data of 52 patients with severe cerebral venous sinus thrombosis who underwent endovascular treatment in the Department of Neurosurgery, Tianjin Huanhu Hospital from June 2019 to June 2022 were retrospectively analyzed. There were 20 males and 32 females, with an age of (40.1±13.6) years(range:18 to 66 years). Forty-five healthy physical examinees were included in the control group. High-resolution MRI was used to stage the thrombus, with 11 cases in the acute group, 28 cases in the subacute group, and 13 cases in the chronic group. Thrombus specimens were obtained through endovascular treatment, and the fluorescence intensity of NET in peripheral blood at different time points was analyzed by immunofluorescence contrast,including the double-stranded DNA structure and adhesion protein components (citrolinated histone H3 (CitH3), myeloperoxidase-DNA complex(MPO-DNA), neutrophil elastase (NE)). The NET markers were determined by ELISA. Spearman rank correlation analysis was used to analyze the correlation between the NET markers in peripheral blood of patients with severe cerebral venous sinus thrombosis in the acute and subacute phases and the volume of venous sinus thrombus, the degree of venous sinus recanalization after treatment, and the discharge modified Rankin scale(mRS)score. The accuracy of NET markers in predicting the prognosis of patients with severe cerebral venous sinus thrombosis was analyzed by drawing receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: The results of immunofluorescence staining and ELISA showed that no NET structure was formed in the peripheral blood of the control group, while CitH3, MPO-DNA and NE levels in the peripheral blood of CVST patients were increased, among which the acute stage group was the highest, followed by the subacute group, and the chronic group was the lowest. Spearman correlation analysis showed that CitH3, MPO-DNA and NE levels in peripheral blood of patients in acute group and subacute group were positively correlated with thrombus volume and mRS score at discharge (P<0.05). The levels of CitH3 and MPO-DNA in peripheral blood of patients with complete venous sinus recanalization were lower than those of patients with partial venous sinus recanalization (P<0.01). ROC curve analysis results showed that MPO-DNA and NE had no predictive ability for the prognosis of CVST patients (P values were 0.614 and 0.324, respectively), and the AUC of CitH3 was 0.800 (95%CI: 0.638~0.962, P=0.032), the best cut-off value was 13.5 μg/L, the sensitivity was 100%, and the specificity was 58.8%. Conclusions: A large number of NET are formed in patients with severe cerebral venous sinus thrombosis in acute stage. Patients with severe cerebral venous sinus thrombosis in acute stage and subacute stage with high peripheral blood NET content has a low rate of complete sinus revascularization and poor neurological function recovery after treatment.

Adipose Triglyceride Lipase–Mediated Adipocyte Lipolysis Exacerbates Acute Pancreatitis Severity in Mouse Models and Patients

Dyslipolysis of adipocytes has played a critical role in various diseases. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme in adipocyte autonomous lipolysis. However, whether the degree of adipocyte lipolysis relates to the prognoses in acute pancreatitis (AP) and the role of ATGL mediated lipolysis in the pathogenesis of AP remains elusive. The visceral adipose tissue (VAT) consumption rate (VATR) in the acute stage was measured in both AP patients and mouse models. Lipolysis levels and ATGL expression were detected in caerulein (CER)-induced AP models. CL316,243, a lipolysis stimulator, and adipose tissue-specific ATGL knockout (AAKO) mice were used to further investigate the role of lipolysis in AP. The ATGL-specific inhibitor, Atglistatin, was performed in C57Bl/6N and ob/ob AP models. This study found that increased VATR in the acute phase was independently associated with adverse prognoses in AP patients, which was validated in mice AP models. Lipolysis of adipocytes was elevated in AP mice. Stimulation of lipolysis could aggravate AP. Genetic blockage of ATGL specifically in adipocytes was able to alleviate the damage to AP. The application of Atglistatin could effectively protect against AP in both lean and obese mice. These findings demonstrated that ATGL-mediated adipocyte lipolysis exacerbates AP and highlighted the therapeutic potential of ATGL as a drug target for AP.