Mesenteric Blood Research Articles

Salvianolic acid B improves the microcirculation in a mouse model of sepsis through a mechanism involving the platelet receptor CD226.

Salvianolic acid B (SalB) demonstrates diverse clinical applications, particularly in cardiovascular and cerebral protection. This study primarily investigated the effects of SalB on sepsis. The model of sepsis via caecal ligation puncture (CLP) was established in male C57BL/6 mice. Therapeutic effects of SalB on hepatic and pulmonary injury, inflammatory responses and microcirculatory disturbances in sepsis were evaluated. Platelet aggregation and adhesion were measured via flow cytometry and an adhesion test. After overexpression of platelet-related activating molecules by 293T cells, the efficient binding of SalB and platelet CD226 molecules was further evaluated. Finally, neutralizing antibody experiments were used to assess the mechanism of SalB in alleviating the progression of sepsis. SalB mitigated hepatic and pulmonary impairments, reduced inflammatory cytokine levels and enhanced mesenteric microvascular blood flow in septic mice. SalB enhanced CLP-induced reduction of platelet count and platelet pressure cumulative volume. SalB reduced platelet adhesion to endothelial cells and platelet aggregation to leukocytes. A high binding efficiency was observed between SalB and the platelet adhesion molecule CD226. Ex vivo, interactions between SalB and platelets from CD226-knockout mice were markedly decreased. In vivo administration of CD226 neutralizing antibodies significantly delayed disease progression and enhanced mesenteric microcirculation in septic mice. In our murine model of sepsis, treatment with SalB improved the microcirculatory disturbance and hindered the progression of sepsis by inhibiting platelet CD226 function. Our results suggest SalB is a promising therapeutic approach to the treatment of sepsis.

The effects of nutrition on mesenteric oxygenation among neonates with neonatal encephalopathy: a randomized clinical trial.

We aimed to evaluate the effects of minimal enteral nutrition (MEN) on mesenteric blood flow and oxygenation with Doppler USG and Near Infrared Spectroscopy (NIRS) during therapeutic hypothermia (TH) in babies with HIE. This prospective, randomized-controlled study was composed of infants receiving MEN (study group, n = 30) and infants who were not fed (control group, n = 30) during hypothermia. Infants were monitored continuously with NIRS and mesenteric blood flow velocities were measured with Doppler USG before and after feeding. The mean gestational age and birth weight for the study and control group were 38.73 ± 1.5-39.09 ± 1.02 weeks and 3076 ± 280.4-3295 ± 391 grams, respectively. Time to reach full enteral nutrition and hospital stay were significantly shorter in the study group (p = 0.049, p = 0.016). Infants in the study group experienced less feeding intolerance (p = 0.006). No infant developed necrotizing enterocolitis (NEC) in both groups. No difference was determined in pre- and post-feeding cerebral rSO2 measurements during TH and normothermia. Mesenteric rSO2, CSOR, and mesenteric blood flow measurements in the study group during normothermia were significantly increased, respectively (p = 0.03, p < 0.01, p < 0.01). In our study, we observed that MEN during TH does not lead to a significant change in cerebral and mesenteric oxygenation. Although we did not observe an increase in blood flow and oxygenation, the absence of NEC and a lower incidence of feeding intolerance in the study group may suggest that feeding during TH is safe and feasible. MEN during TH treatment does not lead to a significant change in cerebral and mesenteric oxygenation. This is the first study evaluating the effects of MEN on mesenteric oxygenation and blood flow velocities in infants with hypoxic-ischemic encephalopathy during TH with Doppler USG and NIRS, concomitantly. MEN during TH may be safe and feasible.

Mesenteric blood flow and muscle sympathetic nerve activity during vasovagal syncope.

Vasovagal syncope is thought to be mediated by a progressive fall in cardiac output secondary to venous pooling of blood in the splanchnic circulation. How and when this occurs before syncope has not been determined. A total of 20 patients who became hypotensive during head-up tilt (age 40.9 ± 3.4 years; 10 females) were divided into two groups-the glyceryl trinitrate (GTN) group (n = 12) and the vasovagal syncope (VVS) group (n = 8) - on the basis of whether or not nitroglycerine provocation was required. They were compared with a control group (age 38.6 ± 3.3; 8 females; n = 13). Hemodynamics, including superior mesenteric artery blood flow (SMABF) and muscle sympathetic nerve activity (MSNA) were recorded continuously during early tilt, presyncope and recovery. We used pixel-weighting to calculate average velocity from the pulsed Doppler velocity envelope. During baseline and early tilt, resistance to mesenteric blood flow was lower in the VVS group: 0.30 ± 0.02 to 0.30 ± 0.02mmHg/ml/min versus controls 0.30 ± 0.03 to 0.38 ± 0.04mmHg/ml/min (p = 0.05). During presyncope, as blood pressure and stroke volume gradually fell, SMABF was higher in the VVS group, falling from 370 ± 46 to 248 ± 35ml/min, versus controls, falling from 342 ± 51 to 233 ± 19 (p = 0.03). At this time, MSNA was lower in the VVS group than controls: 39 ± 4 to 34 ± 3 bursts/min versus 45 ± 2 to 48 ± 3 (p = 0.001). During presyncope, increased splanchnic blood flow may pool more blood in capacitance vessels resulting in decreased venous return and cardiac output. This may be secondary to decreased vasoconstrictor sympathetic activity.

Management of gastroschisis in an extremely low birth weight infant: report of a case

BackgroundGastroschisis is a rare congenital anomaly in which abdominal organs herniate through a defect in the abdominal wall. Managing gastroschisis in extremely low birth weight (ELBW) infants presents significant challenges because of their immature physiologies and increased risk of complications.Case presentation: This report discusses the case of a female ELBW infant born via an emergency cesarean section at 29 weeks of gestation, weighing 768 g, who had a prenatal diagnosis of gastroschisis. Postnatal management included immediate surgical intervention using a hand-made silo manufactured from expanded polytetrafluoroethylene (ePTFE) sheets that were sutured to the patient’s abdominal wall to accommodate her small abdominal cavity and preserve mesenteric blood flow. Necrotizing enterocolitis with bowel perforation emerged as a complication, which led to the excision of a 10 cm segment of the ileum and the creation of an ileostomy. The infant experienced insufficient weight gain and liver dysfunction. However, she was eventually discharged on day 142 of life, weighing 2774 g, on oral feeding, without significant complications.ConclusionsThis case emphasizes how prematurity significantly affected the patient’s clinical outcomes, and highlights the importance of individualized management strategies. Our experience demonstrates that custom silo placement allows for the size to be adapted to the abdominal defect, and highlights the critical need to prioritize postnatal bowel perfusion in ELBW infants with gastroschisis.

A Comparative Study of Different Modes of Noninvasive Ventilation as Postextubation Respiratory Support and Their Effect on Hemodynamic Changes in Preterm infants

Abstract Background Noninvasive respiratory support has reduced the need for invasive mechanical ventilation (MV). This may reduce the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. There are many different forms of noninvasive respiratory support which include nasal continuous positive airway pressure (NCPAP), Non-invasive high-frequency oscillatory ventilation (NHFOV) and High velocity nasal insufflation (HVNI). Little is known about the hemodynamic changes that occur during NIV, particularly during the weaning phase when lung compliance has improved. Aim of the Work To evaluate the outcome of NHFOV and Hi-VNI Vapotherm in comparison to nasal CPAP as a post extubation noninvasive respiratory support in preterm neonates. 2ry aim is to assess hemodynamic changes during periods of non-invasive respiratory support including echocardiographic, cerebral blood flow and mesenteric blood flow changes. Study Design This was a randomized control prospective study at Ain Shams Children Hospital, Cairo, Egypt. conducted on 61 mechanically ventilated preterm neonates 32-36 weeks gestational age with RDS, who were on invasive ventilatory support then extubated to non-invasive mode: Group A, 21 preterm neonates extubated on NCPAP. Group B, 20 preterm neonates extubated on NHFOV and Group C, 20 preterm extubated on Hi-VNI Vapotherm. The Three groups were studied for the need for re-intubation within the first 24 hours after extubation, length of hospital stay and duration of non- invasive ventilation (NIV), Retinopathy of prematurity (ROP), air leak syndromes, Intraventricular hemorrhage (IVH), Necrotizing enterocolitis (NEC), nasal trauma, Bronchopulmonary dysplasia (BPD) and mortality. Also assessing hemodynamic changes during and after weaning of non-invasive respiratory support including echocardiography, Anterior cerebral artery resistive index (ACA) RI, Middle cerebral arteries resistive index (MCA) RI, and superior mesenteric artery resistive index (SMA) RI. Results PaCO2 was unchanged from preextubation levels after weaning in the NCPAP and NHFOV but increased significantly after weaning from vapotherm. NCPAP had the shortest length of hospital stay median (IQR) 18 while the NHFOV has the longest duration of hospital stay median (IQR) 28. NHFOV had the least failure rate10% while post extubation to Vapotherm had the highest failure rate 40%, yet this did not reach statistical significance. Significant association found between failure on vapotherm and birth weight less than or equal to 1.75 kg with OR (95% CI) of 77.00 (4.114 – 1441.049) and with p-value = 0.004. A significant higher incidence of mortality was found in vapotherm failed group as compared to the succeed group (75% vs. 0%, p = 0.03). There was significantly higher nasal trauma among NHFOV group compared to the NCPAP and Vapotherm groups (P = 0.001). NHFOV had the least mortality rate 0% while post extubation to Vapotherm had the highest mortality rate 30%, yet this did not reach statistical significance. NCPAP had the least incidence of sepsis while the vapotherm had the highest incidence (P = 0.02). No significant difference between the 3 modes of noninvasive respiratory support in the occurrence of comorbidities as NEC, IVH, ROP and BPD. By Doppler echocardiography, NHFOV showed that both RVO, SVC flow significantly increased after weaning. ACA RI significantly increased after weaning from NHFOV. Also, it showed significant increase in RVO after weaning vapotherm with no significant effect on cerebral blood flow. NCPAP didn’t have significant effect on systemic &amp; pulmonary venous return by Doppler echocardiography. Although it showed that both ACA and MCA RI significantly increased after weaning. Conclusion Overall, these findings suggest that NHFOV may be a favorable option for respiratory support in preterm infants following extubation, as it was associated with better outcomes compared to NCPAP and Vapotherm. However, further research is needed to fully understand the potential benefits and risks of each mode of noninvasive respiratory support in this population. Infants in the Hi-VNI Technology group had significantly lower nasal trauma scores than those in the NCPAP and NHFOV groups with increased failure rate in preterm infants with a birth weight less than or equal to 1.75 kgs.

Abstract 59: Beclin-1-Dependent Autophagy Prevents Hyperaldosternism-Induced Endothelial Dysfunction And Hypertension

Hyperaldosteronism (HA), characterized by the overproduction of aldosterone (Aldo), leads to cardiovascular damage, including endothelial dysfunction. Beclin-1 (Becn1) is a key protein regulating autophagy, a recycling process for unwanted components. Whether HA disturbs autophagic flux in endothelial cells via Becn1 is unknown. We hypothesize that Becn1-dependent autophagic flux will improve endothelial function and inhibit the hypertension (HTN) in HA. 10-to-12-week-old male C57BL/6J (WT) or Becn1 knock-in mice (Becn1 Tg ) were infused with aldosterone for 14 days (600 µg/kg/day). Vascular function was studied in mesenteric arteries (MA) and blood pressure was analyzed by radiotelemetry. HA disrupted MA autophagic flux characterized by accumulation of LC3A/B and p62 and reduction in Becn1 expression and activity followed by suppressed acetylcholine (ACh)-induced vasodilation (% relaxation) in WT [WT: 91.5±1.1 vs HA: 56.7±2.7], whereas Becn1 Tg mice were protected from HA-induced HTN [mean blood pressure (mmHg) – WT_Aldo: 149.1±1.2 vs BCN1_Aldo: 118.1±0.8] and endothelial dysfunction [HA_Becn1 Tg : 92.8±2.9]. Given the link between the immune system and cardiovascular diseases, we investigated whether HA reduces autophagic flux and BCN1 in immune cells. HA led to the accumulation of LC3A/B and p62, and decreased BCN1 activity in peritoneal cavity cells of WT mice, however bone marrow transplant from Becn1 Tg mice into WT mice did not confer protection against HA-induced changes in vascular reactivity [WT to WT_HA: 51.2±1.3 vs Becn1 Tg to WT_HA: 53.8±1.9]. As a pharmacological approach, we accelerated autophagic flux by treating mice with spermidine (3 mM for 7 days), which subsequently improved endothelial function in HA [HA: 52.7±3.9 vs HA+spermidine: 88.9±3.9]. To assess the direct impact of Aldo on disrupting autophagy flux in endothelial cells, we treated mesenteric endothelial cells (MEC) with Aldo (0.1 µM for 24 hours). This treatment resulted in the accumulation of LC3A/B and p62 proteins and a reduction in BCN1 activity, accompanied by an upregulation in the mRNA expression of pro-inflammatory cytokines. All these effects were prevented by spermidine (100 uM for 3h). These findings reveal a novel pathway in HA-associated endothelial dysfunction and HTN, where Aldo disrupts autophagic flux and inflammation by suppressing BCN1 activity, positioning BCN1 as a pharmacological target for cardiovascular outcomes in HA.

Human Infant Fecal Microbiota Differentially Influences the Mucosal Immune Pathways Upon Influenza Infection in a Humanized Gnotobiotic Pig Model

In this study, we evaluated the impact of human gut microbiota on the immune pathways in the respiratory tract using a gnotobiotic (Gn) piglet model. We humanized piglets with rural and urban infant fecal microbiota (RIFM and UIFM, respectively) and then infected them with a H1N1 swine influenza virus. We analyzed the microbial diversity and structure of the intestinal and respiratory tracts of the piglets before and after the influenza virus infection and measured the viral load and immune responses. We found that the viral load in the upper respiratory tract of UIFM transplanted piglets was higher than their rural cohorts (RIFM), while virus-specific antibody responses were comparable. The relative cytokine gene expression in the tracheobronchial (respiratory tract) and mesenteric (gastrointestinal) lymph nodes, lungs, blood, and spleen of RIFM and UIFM piglets revealed a trend in reciprocal regulation of proinflammatory, innate, and adaptive immune-associated cytokines as well as the frequency of T-helper/memory cells, cytotoxic T cells, and myeloid immune cell subsets. We also observed different phylum-level shifts of the fecal microbiota in response to influenza virus infection between the two piglet groups, suggesting the potential impact of the gut microbiota on the immune responses to influenza virus infection and lung microbiota. In conclusion, Gn piglets humanized with diverse infant fecal microbiota had differential immune regulation, with UIFM favoring the activation of proinflammatory immune mediators following an influenza virus infection compared to their rural RIFM cohorts. Furthermore, Gn piglets can be a useful model in investigating the impact of diverse human microbiota of the gastrointestinal tract, probably also the respiratory tract, on respiratory health and testing specific probiotic- or prebiotic-based therapeutics.

Quantifying and visualizing abdominal hemodynamics in patients with Fontan circulation by 4D phase-contrast flow magnetic resonance imaging at 1.5 T

BackgroundLiver fibrosis has been recognized as a long-term morbidity associated with Fontan circulation (Fontan-associated liver disease, FALD). The pathophysiology of FALD is not completely understood and abnormal flow dynamics may be associated with this condition. Liver hemodynamics can be quantitatively evaluated with four-dimensional phase-contrast flow magnetic resonance imaging (4D PC flow MRI). The study aimed to evaluate suitability of liver 4D PC flow MRI in Fontan patients and relate flow measurements to normal values and FALD severity. Patients and methodsTwenty-two Fontan patients were examined by 4D PC flow MRI at 1.5 Tesla to assess mesenteric, portal, splenic, and hepatic venous blood flow. Severity of FALD was graded based on routine screening, including abdominal ultrasound and laboratory tests. ResultsMedian age was 18.5 (interquartile range, IQR 15.5–20.2) years. FALD was graded as “none or mild” in 16 and as “moderate to severe” in six cases. Ten patients presented at least one feature of portal hypertension (ascites, splenomegaly, or thrombocytopenia). For the entire cohort, blood flow in the superior mesenteric, splenic, and portal vein was lower than reported in the literature. No significant differences were observed in relation to FALD severity. Features of portal hypertension were associated with a higher splenic vein blood flow (0.34 ± 0.17 vs. 0.20 ± 0.07 l/min, p = 0.046). Splenic vein blood flow was negatively correlated to platelet count (r = −0.590, p = 0.005). Conclusions4D PC flow MRI appears suitable to assess liver hemodynamics in Fontan patients and integration into clinical follow-up might help to improve our understanding of FALD.

From Warm to Cold: Feeding Cold Milk in Preterm Infants with Uncoordinated Oral Feeding Patterns.

Premature infants frequently face feeding challenges due to disrupted coordination of sucking, swallowing, and breathing, increasing their risk of dysphagia. There are few effective treatment options available for these infants. In adults experiencing dysphagia, consuming cold foods or liquids can be an effective strategy. This method stimulates the sensory receptors in the pharyngeal mucosa, promoting safer and more effective swallowing. We have previously demonstrated that short-duration feeding (5 swallows) with cold liquid significantly reduces dysphagia in preterm infants; however, the impact of extended cold milk feeding remains unexplored. This study aims to assess the safety of cold milk feedings in preterm infants diagnosed with uncoordinated feeding patterns and its effect on feeding performance. Preterm infants with uncoordinated feeding patterns (n=26) were randomized to be fed milk at either room or cold temperatures using an experimental, randomized crossover design. We monitored axillary and gastric content temperatures, mesenteric blood flow, and feeding performance. The findings suggest that preterm infants can safely tolerate cold milk without any clinically significant changes in temperature or mesenteric blood flow, and it may enhance certain aspects of feeding performance. These results suggest that cold milk feeding could be a safe therapeutic option for preterm infants. These results highlight the potential for further comprehensive studies to explore the use of cold milk as an effective therapeutic approach for addressing feeding and swallowing difficulties in preterm infants. Registered at clinicaltrials.org #NCT04421482.

Hybrid treatment of recurrent venous mesenteric thrombosis with small intestinal necrosis

The article presents a clinical case of a 39-year-old patient with thrombosis and postoperative rethrombosis of the superior mesenteric vein. The disease was complicated by the small intestine necrosis and abdominal surgical infection. Successful thrombectomy and bowel resection made it possible to restore mesenteric blood supply, to stabilize the patient’s condition and to perform an enteroenteroanastomosis. Due to antithrombin III deficiency, rethrombosis in the early postoperative period was complicated by anastomotic leak, unformed intestinal fistula and peritonitis. A hybrid treatment (surgical, parasurgical and conservative) was performed, which included selective infusion of a thrombolysis activator at the superior mesenteric artery mouth. The patient recovered.Clinical and laboratory manifestations of superior mesenteric vein thrombosis, in contrast to acute circulatory disorders in the arteriomesenteric system, are nonspecific and do not always allow timely diagnosis of intestinal ischemia. MSCT angiography identifies venous mesenteric thrombosis in most cases. The ineffectiveness of anticoagulant therapy against the background of antithrombin III deficiency caused superior mesenteric vein thrombosis and rethrombosis. The treatment of the small intestine critical postoperative ischemia included an increase in the volume of antithrombin III and frozen plasma intravenous infusion and selective administration of a thrombolysis activator (actilyse) into the superior mesenteric artery, which made it possible to restore the arteriolovenular intramural blood flow of the small intestine and to prevent another stem rethrombosis of the superior mesenteric vein. Laparostomy using a silicone plate made it possible to constantly monitor the course of the abdominal infectious process and to make timely decisions about the next intervention if medically required. The vacuum assisted design provided permanent lavage of the abdominal cavity without trauma to the soft tissues of the abdominal wall and presenting intestinal loops.

Is choline deficiency an unrecognized factor in necrotizing enterocolitis of preterm infants?

We undertook this review to determine if it is plausible that choline or phosphatidylcholine (PC) deficiency is a factor in necrotizing enterocolitis (NEC) after two clinical trials found a dramatic and unexpected reduction in NEC in an experimental group provided higher PC compared to a control group. Sources and amounts of choline/PC for preterm infants are compared to the choline status of preterm infants at birth and following conventional nutritional management. The roles of choline/PC in intestinal structure, mucus, mesenteric blood flow, and the cholinergic anti-inflammatory system are summarized. Low choline/PC status is linked to prematurity/immaturity, parenteral and enteral feeding, microbial dysbiosis and hypoxia/ischemia, factors long associated with the risk of developing NEC. We conclude that low choline status exists in preterm infants provided conventional parenteral and enteral nutritional management, and that it is plausible low choline/PC status adversely affects intestinal function to set up the vicious cycle of inflammation, loss of intestinal barrier function and worsening tissue hypoxia that occurs with NEC. In conclusion, this review supports the need for randomized clinical trials to test the hypothesis that additional choline or PC provided parenterally or enterally can reduce the incidence of NEC in preterm infants. IMPACT STATEMENT: Low choline status in preterm infants who are managed by conventional nutrition is plausibly linked to the risk of developing necrotizing enterocolitis.

No difference in postprandial mesenteric blood flow between healthy younger and elderly individuals

We recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in patients with Parkinson's disease compared to age- and sex-matched healthy controls. Since both groups showed substantial inter-individual variations, we extended the cohort of controls with a group of young individuals to investigate possible age-related effects. Seventeen healthy young subjects aged < 30 years and 17 elderly subjects aged > 50 years underwent serial PC-MRI to measure the postprandial blood flow response in the SMA after ingestion of a standardized liquid test meal (∼400 kcal). Postprandial blood flow dynamics in SMA did not differ between young and elderly subjects. A noticeable inter-individual variation in postprandial intestinal blood flow increase was found, and approximately 30% of the variation could be explained by the preprandial blood flow. Regardless of age, some subjects showed a remarkable transient SMA blood flow increase immediately after meal intake. This study provides tentative evidence that postprandial blood flow dynamics in SMA in healthy young and elderly subjects do not substantially differ, indicating that age is without impact on vascular response in SMA as an indicator for regulation of mesenteric perfusion in response to food intake.

Microbially conjugated bile salts found in human bile activate the bile salt receptors TGR5 and FXR.

Bile salts of hepatic and microbial origin mediate interorgan cross talk in the gut-liver axis. Here, we assessed whether the newly discovered class of microbial bile salt conjugates (MBSCs) activate the main host bile salt receptors (Takeda G protein-coupled receptor 5 [TGR5] and farnesoid X receptor [FXR]) and enter the human systemic and enterohepatic circulation. N-amidates of (chenodeoxy) cholic acid and leucine, tyrosine, and phenylalanine were synthesized. Receptor activation was studied in cell-free and cell-based assays. MBSCs were quantified in mesenteric and portal blood and bile of patients undergoing pancreatic surgery. MBSCs were activating ligands of TGR5 as evidenced by recruitment of Gsα protein, activation of a cAMP-driven reporter, and diminution of lipopolysaccharide-induced cytokine release from macrophages. Intestine-enriched and liver-enriched FXR isoforms were both activated by MBSCs, provided that a bile salt importer was present. The affinity of MBSCs for TGR5 and FXR was not superior to host-derived bile salt conjugates. Individual MBSCs were generally not detected (ie, < 2.5 nmol/L) in human mesenteric or portal blood, but Leu-variant and Phe-variant were readily measurable in bile, where MBSCs comprised up to 213 ppm of biliary bile salts. MBSCs activate the cell surface receptor TGR5 and the transcription factor FXR and are substrates for intestinal (apical sodium-dependent bile acid transporter) and hepatic (Na+ taurocholate co-transporting protein) transporters. Their entry into the human circulation is, however, nonsubstantial. Given low systemic levels and a surplus of other equipotent bile salt species, the studied MBSCs are unlikely to have an impact on enterohepatic TGR5/FXR signaling in humans. The origin and function of biliary MBSCs remain to be determined.

Efficacy and safety analysis of AcoStream thrombus aspiration device in the treatment of acute superior mesenteric artery embolism.

Acute superior mesenteric artery embolism is a life-threatening disease caused by the abrupt interruption of mesenteric blood circulation, and the prognosis is very poor. Several studies have confirmed the efficacy and safety of percutaneous mechanical thrombectomy in acute superior mesenteric artery embolism, however, there are currently no literature reports on the latest percutaneous mechanical thrombectomy device-AcoStream™. In the present report, we summarize a series of cases and share our surgical experiences. The clinical data of 10 patients (six men and four women, mean age 77.6 ± 7.4years) with acute superior mesenteric artery embolism treated by AcoStream™ in our center from December 2022 to December 2023 were retrospectively analyzed. Based on the literature, we summarized the diagnosis, therapy, and surgical experience of acute superior mesenteric artery embolism. Percutaneous mechanical thrombectomy was performed for all the patients. The success rate of surgery reached 100% and no perioperative complications occurred. Abdominal pain was significantly relieved and the abdominal signs gradually disappeared in eight patients, while the other two patients still complained of abdominal pain during hospitalization, and eventually, they underwent resection of necrotic bowel. All the patients' symptoms were significantly relieved and they were smoothly discharged from the hospital. As shown in the present study, percutaneous mechanical thrombectomy using AcoStream™ is minimally invasive, safe, and efficient in the initial stage of acute superior mesenteric artery embolism. We believe that percutaneous mechanical thrombectomy can be a promising alternative in selected cases.

A190 HELICOBACTER PYLORI INDUCES AN AUTO-REACTIVE PHENOTYPE IN PINK1 DEFICIENT MICE THAT CORRELATES WITH MOTOR DYSFUNCTION

Abstract Background Parkinson’s disease (PD) is a chronic neurodegenerative disorder. Several genetic predispositions, including the PTEN-induced kinase 1 (PINK1) mutation, have been implicated in early onset family cases. Besides the loss of dopaminergic neurons in the brain, PD patients have a unique immune phenotype that includes increased inflammation, blood serum, brain levels of proinflammatory cytokines, brain infiltration with cytotoxic CD8 T cells, and loss of regulatory T cells (Treg) and their anti-inflammatory phenotype. The role of the gut microbiota and gastrointestinal infections are increasingly recognized as a cofactor in PD. One of pathogens associated with the risk of PD is Helicobacter pylori. The prevalence of this Gram-negative bacteria in PD patients is higher than in the general population and its eradication in PD patients improves motor function. Loss of the PD-associated PINK1 alters induced Treg function in vitro. We previously have shown that in PINK1 knock-out (KO) mice, gut infection with Gram-negative bacteria, Citrobacter rodentium, induces mitochondrial antigen presentation (MitAP) to the CD8 T cells that later infiltrate the brain. In this model, PINK1 KO mice develop a Parkinson-like L-DOPA-responsive motor phenotype after four C. rodentium infections. Aims Here we aimed to scrutinize potential role of the H. pylori infection in the induction of motor dysfunction and disbalanced immune tolerance in PINK1 KO mice. Methods In addition to standard behavioural testing, at 2- and 6-months post-infection we performed a multiplex cytokine analysis of gastric homogenates and spectral flow cytometry of gastric lamina propria, mesenteric lymph nodes, blood, spleen, and brain infiltrating immunocytes. As well as in vitro immunocytes response and function assays to H.pylori exposure in PINK1 KO and wild-type (WT) littermate controls. Results We show that infection with H. pylori causes a long-lasting inflammation in the stomach; and local and systemic immune phenotype that remains 6 months post-infection. This phenotype, though present in some WT infected mice, is higher in PINK1 KOs and similarly to PD patients includes a decrease in Treg proportion, FoxP3 downregulation in regulatory T cells, Gata3+ CD4 T cell loss, as well as increase of circulating mitochondrial antigen-specific CD8 T cells. Moreover, the immune phenotype in the H. pylori infected PINK1 KO mice correlates with motor dysfunction and CD8 T cell brain infiltration with no such association seen in the WT mice. Conclusions These results provide insight to the gut-immunity-brain axis in the pathogenesis of Parkinson’s disease, and further investigate the role of Gram-negative bacteria in the establishment of immune tolerance-autoreactivity balance. Funding Agencies ASAP

Efficacy of rituximab therapy for 10 patients suffering from systemic lupus erythematosus with intestinal involvement

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

Ultrasound microvascular flow imaging: evaluating fetal mesenteric blood flow and predicting postnatal surgery in meconium peritonitis

Objective This study explored the characteristics of fetal mesenteric blood flow perfusion across various gestational weeks and evaluated the efficacy of Microvascular Flow (MV-Flow) imaging technology in assessing intestinal wall blood flow in fetuses with meconium peritonitis (MP). Method In this retrospective study, we analyzed 35 fetuses with MP and 160 healthy fetuses. We examined the correlation between the Vascular Index (VI) of mesenteric perfusion and gestational age, conducted an analysis comparing MP operative and non-operative groups, and developed a predictive model for surgical intervention. Results The VI value demonstrated no significant change with increasing gestational age (correlation coefficient = 0.005, p = 0.946). For healthy fetuses, VI ranged approximately from 34.66% to 67.26% using the automatic ellipse method. The MP operative group exhibited significantly more cesarean deliveries (100% vs. 52.9%, p = 0.003), shorter gestational periods (34.76 ± 2.16 weeks vs. 37.48 ± 1.55 weeks, p < 0.001), lower birth weights (2762.14 ± 452.76 g vs. 3225.88 ± 339.98 g, p = 0.003), more persistent ascites (92.9% vs. 52.9%, p = 0.021), more frequent intestinal wall echo reductions (57.1% vs. 5.9%, p = 0.004), and lower VI (18.57 ± 5.51% vs. 39.41 ± 7.02%, p < 0.001). A predictive model was established: Logit (P)=8.86 - (0.37* VI) + (1.49* ascites), yielding an area under the curve of 0.857, with 78.6% sensitivity and 88.2% specificity. The VI value was significantly associated with the need for postnatal surgery (OR = 0.689, 95% confidence interval: 0.511 − 0.929, p = 0.015). A Receiver Operating Characteristic curve analysis for VI in predicting postnatal surgery showed an area under the curve of 0.971, with an optimal cutoff value of 35%, achieving 91% sensitivity and 94.4% specificity. Conclusion MV-Flow imaging effectively quantified fetal bowel wall blood flow perfusion. There was no significant change in VI across different gestational weeks. Significantly lower VI values in MP fetuses indicated an increased risk of intestinal wall necrosis and the potential need for postnatal surgical intervention.

Duration of systemic alteration in vasomotor function of microvascular endothelium caused by the influenza A(H1N1)pdm09 virus

Introduction. The influenza A virus (IAV) can infect vascular endothelial cells and cause activation and/or dysfunction of the endothelium. Previously, we have shown that the influenza A(H1N1)pdm09 virus leads to alteration in functional activity of blood vessels in different vascular beds, and also causes various histopathological changes in pulmonary blood vessels of Wistar rats in the acute period of infection. Aim – to study the duration of systemic alteration in vasomotor function of microvascular endothelium caused by the influenza A(H1N1)pdm09 virus. Materials and methods. The Wistar rats were intranasally infected with the influenza A/St. Petersburg/48/16 (H1N1)pdm09 virus and at 1, 4, 7, 14, 21, 30, 60 and 90 days post infection (dpi) they were anesthetized and necropsied. The expression level of endothelial nitric oxide synthase (eNOS) was determined in mesenteric vascular endothelium by immunohistochemistry. The vasomotor activity of the mesenteric arteries was studied using wire myography. Results. The influenza A(H1N1)pdm09 virus causes a decrease in eNOS expression by 13–39 % within 60 dpi (p&lt;0.05). In addition, the influenza virus also reduces the maximal response of mesenteric arteries to the vasodilator by 74–108 % within 21 days (p&lt;0.0001) and reduces the response by 16–26 % within 30 and 60 dpi (p&lt;0.0001), respectively, and also increases the maximum response of the arteries to the vasoconstrictor by 26–57 % within 30 dpi (p&lt;0.05). It should be noted that such long-term changes are observed while virus is eliminated by the 7th dpi. Conclusion. The influenza A(H1N1) pdm09 virus causes long-term endothelial dysfunction in the Wistar rats which is characterized by the reduced expression of eNOS in mesenteric microvascular endothelium within 60 dpi, decrease of the maximal response of mesenteric microvessels to vasodilator within 60 dpi and increase of the maximal response to vasoconstrictor within 30 dpi. Alterations of systemic functional activity of mesenteric microvessels in rats infected with influenza A(H1N1)pdm09 virus are registered in absence of the reproduction of virus in mesenteric blood vessels while virus is eliminated from pulmonary tissues by the 7th dpi.

Clinical Dilemma Involving Treatments for Very Low-Birth-Weight Infants and the Potential Risk of Necrotizing Enterocolitis: A Narrative Literature Review.

Necrotizing enterocolitis (NEC) is a critical gastrointestinal emergency with substantial morbidity and mortality risks, especially for very low-birth-weight (VLBW) infants, and unclear multifactorial pathophysiology. Whether common treatments for VLBW infants increase the NEC risk remains controversial. Indomethacin (utilized for patent ductus arteriosus) offers benefits but is concerning because of its vasoconstrictive impact on NEC susceptibility. Similarly, corticosteroids used to treat bronchopulmonary dysplasia may increase vulnerability to NEC by compromising immunity and altering the mesenteric blood flow. Histamine-2 receptor blockers (used to treat gastric bleeding) may inadvertently promote NEC by affecting bacterial colonization and translocation. Doxapram (used to treat apnea) poses a risk of gastrointestinal disturbance via gastric acid hypersecretion and circulatory changes. Glycerin enemas aid meconium evacuation but disrupt microbial equilibrium and trigger stress-related effects associated with the NEC risk. Prolonged antibiotic use may unintentionally increase the NEC risk. Blood transfusions for anemia can promote NEC via interactions between the immune response and ischemia-reperfusion injury. Probiotics for NEC prevention are associated with concerns regarding sepsis and bacteremia. Amid conflicting evidence, this review unveils NEC risk factors related to treatments for VLBW infants, offers a comprehensive overview of the current research, and guides personalized management strategies, thereby elucidating this clinical dilemma.

Pathological and virological findings of type I interferon receptor knockout mice upon experimental infection with Heartland virus

Heartland virus (HRTV) causes generalized symptoms, severe shock, and multiple organ failure. We previously reported that interferon-α/β receptor knockout (IFNAR-/-) mice infected intraperitoneally with 1 × 107 tissue culture-infective dose (TCID50) of HRTV died, while those subcutaneously infected with the same dose of HRTV did not. The pathophysiology of IFNAR-/- mice infected with HRTV and the mechanism underlying the difference in disease severity, which depends on HRTV infection route, were analyzed in this study. The liver, spleen, mesenteric and axillary lymph nodes, and gastrointestinal tract of intraperitoneally (I.P.) infected mice had pathological changes; however, subcutaneously (S.C.) infected mice only had pathological changes in the axillary lymph node and gastrointestinal tract. HRTV RNA levels in the mesenteric lymph node, lung, liver, spleen, kidney, stomach, intestine, and blood were significantly higher in I.P. infected mice than those in S.C. infected mice. Chemokine ligand-1 (CXCL-1), tumor necrosis factor (TNF)-α, interleukin (IL)-12, interferon (IFN)-γ, and IL-10 levels in plasma of I.P. infected mice were higher than those of S.C. infected mice. These results indicated that high levels of viral RNA and the induction of inflammatory responses in HRTV-infected IFNAR-/- mice may be associated with disease severity.