The role of myeloid differentiation of hematopoietic stem cells in pregnancy immunological tolerance: a systematic review.

The present research aimed to conduct a comprehensive critical analysis of existing literature, focusing on the differentiation of myeloid cells from hematopoietic stem cells within the context of immunological tolerance during pregnancy. A comprehensive systematic review was conducted by searching databases including PubMed, Scopus Biomedicine, EBSCOhost, ScienceDirect, Embase, Cochrane Library, and Web of Science. The focus was on the role of myeloid differentiation from hematopoietic stem cells in modulating immune tolerance, particularly during pregnancy and in certain disease states where they act to suppress the immune response. The quality of the evidence gathered was assessed using the GRADE rating system. Our analysis maintains objectivity and independence from the outcomes presented. The current systematic review offers a synthesis of existing research on the transformation of hematopoietic stem cells into fibroblasts across different tissue types. A thorough search of databases such as PubMed, EBSCOhost, Embase, ScienceDirect, Cochrane Library, and Web of Science was performed in conjunction with a specialist in medical information to identify original research on the derivation of fibroblasts following hematopoietic stem cell transplantation. This search yielded a total of 159 studies, of which 10 met the criteria for inclusion in this review. Reflecting on the constraints of this preliminary review, further in-depth and scientific investigations are warranted to comprehensively assess the impact of varied treatments, with a recommendation for clinicians to proceed with increased circumspection. The myeloid differentiation pathway of hematopoietic stem cells is pivotal in modulating the immune environment during pregnancy, supporting the sustenance of a healthy gestational period. Future research in this domain is expected to advance our understanding of the immunological processes occurring at the maternal-fetal boundary.

Extramedullary hematopoiesis contributes to enhanced erythropoiesis during pregnancy via TGF-ß signaling.

Red blood cells are the predominant cellular component in human body, and their numbers increase significantly during pregnancy due to heightened erythropoiesis. CD71+ erythroid cells (CECs) are immature red blood cells, encompassing erythroblasts and reticulocytes, constitute a rare cell population primarily found in the bone marrow, although they are physiologically enriched in the neonatal mouse spleen and human cord blood. Presently, the mechanisms underlying the CECs expansion during pregnancy remain largely unexplored. Additionally, the mechanisms and roles associated with extramedullary hematopoiesis (EMH) of erythroid cells during pregnancy have yet to be fully elucidated. In this study, our objective was to examine the underlying mechanisms of erythroid-biased hematopoiesis during pregnancy. Our findings revealed heightened erythropoiesis and elevated CECs in both human and mouse pregnancies. The increased presence of transforming growth factor (TGF)-ß during pregnancy facilitated the differentiation of CD34+ hematopoietic stem and progenitor cells (HSPCs) into CECs, without impacting HSPCs proliferation, ultimately leading to enhanced erythropoiesis. The observed increase in CECs during pregnancy was primarily attributed to EMH occurring in the spleen. During mouse pregnancy, splenic stromal cells were found to have a significant impact on splenic erythropoiesis through the activation of TGF-ß signaling. Conversely, splenic macrophages were observed to contribute to extramedullary erythropoiesis in a TGF-ß-independent manner. Our results suggest that splenic stromal cells play a crucial role in promoting extramedullary erythropoiesis and the production of CECs during pregnancy, primarily through TGF-ß-dependent mechanisms.

Dexmedetomidine after deep brain stimulation for prevention of delirium in elderly patients with Parkinson's disease: protocol for a single-centre, randomised, double-blind, placebo-controlled trial in China.

INTRODUCTION: Parkinson's disease is one of the most common neurodegenerative diseases. Deep brain stimulation (DBS) can improve motor symptoms in patients with middle and late Parkinson's disease, reduce the use of levodopa, and thus reduce drug-related side effects. Postoperative delirium can significantly reduce the short-term and long-term quality of life in elderly patients, which can be alleviated by dexmedetomidine (DEX). However, whether prophylactic DEX could reduce the incidence of postoperative delirium in patients with Parkinson's disease was still unknown. METHODS AND ANALYSIS: This is a single-centre, randomised, double-blinded, placebo-controlled group trial. A total of 292 patients aged 60 years and above elected for DBS will be stratified according to DBS procedure, subthalamic nucleus or globus pallidus interna, then randomly allocated to the DEX group or the placebo control group with a 1:1 ratio, respectively. In the DEX group, patients will be injected with the DEX continuously with an electronic pump at a rate of 0.1 µg/kg/hour for 48 hours at the beginning of general anaesthesia induction. In the control group, normal saline will be administered at the same rate for patients as in the DEX group. The primary endpoint is the incidence of postoperative delirium within 5 days after surgery. Postoperative delirium is assessed by the combination of the Richmond Anxiety Scale and the Confusion Assessment Method (CAM) for the intensive care unit or the 3-minute diagnostic interview for CAM as applicable. The secondary endpoints include the incidence of adverse events and non-delirium complications, the length of stay in the intensive care unit and hospital and all-cause 30-day mortality after the operation. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of Beijing Tiantan Hospital of Capital Medical University (KY2022-003-03). The results of this study will be disseminated through presentation at scientific conferences and publication in scientific journals. TRIAL REGISTRATION NUMBER: NCT05197439.

Intraoperative Hypotension and Postoperative Stroke in Older Patients Who Had Brain Tumor Resections: A Retrospective Cohort Analysis.

BACKGROUND: At some level, intraoperative hypotension causes strokes. Elderly neurosurgical patients are presumably at especially high risk. We tested the primary hypothesis that intraoperative hypotension is associated with postoperative stroke in older patients undergoing brain tumor resection. METHODS: Patients >65 years old who had elective craniotomy for tumor resections were included. The primary exposure was the area under the threshold of intraoperative hypotension. The primary outcome was newly diagnosed ischemic stroke within 30 days, confirmed by scheduled brain imaging. RESULTS: Among 724 eligible patients, 98 (13.5%) had strokes within 30 days after surgery, 86% of which were clinically silent. Curves of lowest mean arterial pressure versus stroke incidence suggested a threshold at 75 mm Hg. Area under the threshold of mean arterial pressure below 75 mm Hg was therefore incorporated into multivariable modeling. There was no association of area below 75 mm Hg and stroke (adjusted odds ratio, 1.00; 95% confidence interval, 1.00-1.00). The adjusted odds ratio for area below 75 mm Hg between 1 and 148 mm Hg × minutes was 1.21 (95% confidence interval, 0.23-6.23). When the area below 75 mm Hg exceeded 1117 mm Hg × minutes, the association remained insignificant. In contrast, malignant tumor and history of previous stroke or myocardial ischemia were associated with strokes. CONCLUSIONS: Postoperative strokes were common in older patients who underwent brain tumor resection, with about 14% having ischemic cerebrovascular events within 30 days, of which 86% were clinically silent. Malignant brain tumors and previous ischemic vascular events were associated with postoperative strokes, but area under 75 mm Hg was not.

Factors associated with artificial airway retention after skull base chordoma resection: A retrospective cohort study.

Background: Chordoma is a malignant bone and soft tissue tumor derived from embryonic notochord remnants, and skull base chordoma accounts for ~1/3 of all chordoma cases. Skull base chordoma is closely related to the brainstem and cranial nerves and has a high recurrence rate. The purpose of this study was to investigate the influence of the timing of tracheal extubation on perioperative pulmonary complications. We also aimed to explore predictors of postoperative artificial airway (AA) retention in patients with skull base chordoma. Methods: This was a single-center, retrospective cohort study. The study population included all skull base chordoma patients undergoing surgical treatment between January 2019 and December 2021 at Beijing Tiantan Hospital. The primary outcome was the incidence of postoperative pulmonary complications. Several patient characteristics were evaluated for potential associations with AA retention. Results: A total of 310 patients with skull base chordoma were enrolled. The frequency of AA retention after surgery for skull base chordoma was 30.97%. The incidence of postoperative pulmonary complications was much lower in those without AA retention (3.74 vs. 39.58%, P < 0.001). Factors with the highest point estimates for the odds of AA retention included body mass index, cranial nerve involvement, maximum tumor diameter, operative method, hemorrhage volume, operative duration and intraoperative mechanical ventilation duration. Conclusions: In this retrospective cohort study, most of the factors associated with postoperative airway retention were closely related to the patient's tumor characteristics. These data demonstrate that respiratory management in patients with skull base chordoma remains an ongoing concern.

Urinary Bladder Matrix Improves Irradiated Wound Healing in a Murine Model.

ABSTRACT: Radiation skin damage is associated with chronic wounds and poor healing. Existing localized treatment modalities have limited benefit. Therefore, there has been increased interest in biologically based solutions. In this study, we aimed to determine the effect of topical urinary bladder matrix (UBM) on chronic irradiated skin wounds using an established murine model. Our findings demonstrated that topical urinary bladder matrix significantly accelerated the healing of irradiated wounds on day 7 (P = 0.0216), day 14 (P = 0.0140), and day 21 (P = 0.0393). Histologically, urinary bladder matrix treatment was associated with higher-quality reorganization and reepithelialization of wounds, an increased density of myofibroblasts (P = 0.0004), and increased collagen deposition (P < 0.0001). In addition, quantitative real-time polymerase chain reaction data demonstrated decreased expression of profibrotic mediators (P = 0.0049). We conclude that urinary bladder matrix may be a useful, noninvasive, adjunctive therapy for the treatment of chronic irradiated skin wounds.

Incidence, Risk Factors, and Outcomes of Hyperbilirubinemia in Adult Cardiac Patients Supported by Veno-Arterial ECMO.

The aims of this study were to evaluate the incidence, risk factors, and outcomes of hyperbilirubinemia in cardiac patients with veno-arterial (VA) ECMO. Data on 89 adult patients with cardiac diseases who received VA ECMO implantation in our hospital were retrospectively reviewed. All patients were divided into the following three groups: 24 in normal group (N, total bilirubin [TBIL] ≤3 mg/dL), 30 in high bilirubin group (HB, 6 mg/dL ≥ TBIL > 3 mg/dL), and 35 in severe high bilirubin group (SHB, TBIL > 6 mg/dL). lg(variables + 1) was performed for nonnormally distributed variables. The incidence of hyperbilirubinemia (>3 mg/dL) was 73%. In a multiple linear regression analysis, lg(peak TBIL + 1) was significantly associated with lg(peak AST + 1) (b-coefficient 0.188, P = 0.001), lg(peak pFHb + 1) (b-coefficient 0.201, P = 0.003), and basic TBIL (b-coefficient 0.006, P = 0.009). Repeated measurement analysis of variance revealed that the main effect for three groups in pFHb and lg(AST + 1) was significant at first 3 days during ECMO. The patients in SHB had low platelets during ECMO and low in-hospital survival rate. Hyperbilirubinemia remains common in patients with VA ECMO and is associated with low platelets and high in-hospital mortality. Hemolysis and liver dysfunction during ECMO and basic high bilirubin levels are risk factors of hyperbilirubinemia.

Protective effects of dexmedetomidine on intestinal ischemia-reperfusion injury.

Dexmedetomidine (DEX) has been hypothesized to possess anti-oxidative properties that may mitigate the damage caused by ischemia-reperfusion (IR) injury. The aim of the present study was to examine the effects of DEX on intestinal contractile activity, inflammation and apoptosis following intestinal IR injury. Intestinal IR injury was induced in rats by complete occlusion of the superior mesenteric artery for 60 min, followed by a 60-min reperfusion period. Rats received an intraperitoneal injection of 25 µg/kg DEX at 30 min prior to the mesenteric IR injury. Following reperfusion, segments of the terminal ileum were rapidly extracted and transferred into an isolated organ bath. The contractile responses to receptor-mediated acetylcholine (Ach) and non-receptor-mediated potassium chloride (KCl) were subsequently examined. Nitric oxide (NO) levels were determined and the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, Bax and Bcl-2 were measured using an enzyme-linked immunosorbent assay. The levels of telomerase and caspase-3 were determined using reverse transcription-quantitative polymerase chain reaction. The results indicated that DEX treatment produced a significant reduction in the IR-induced contractile response to Ach and KCl in the intestinal tissue. Furthermore, DEX appeared to significantly ameliorate intestinal IR injury, in addition to reducing the production of NO. Similar reductions were observed in the intestinal expression levels of TNF-α and IL-6. In addition, DEX treatment resulted in a reduction in the expression levels of Bax in the intestinal tissues, while increasing those of Bcl-2, in addition to significantly increasing the mRNA levels of telomerase and caspase-3. Therefore, the present study indicated that NO, TNF-α and IL-6 may partially contribute to the pathogenesis of intestinal IR injury in addition to the increased expression levels of Bax, Bcl-2, telomerase and caspase-3. These findings suggest that DEX possesses beneficial anti-apoptotic and anti-inflammatory effects in intestinal tissue following bowel injury.

Effects of hydroxyethyl starch (130 kD) on brain inflammatory response and outcome during normotensive sepsis.

BACKGROUND: During sepsis, the dysfunction of blood-brain barrier (BBB) was mediated by inflammation and subsequently caused sepsis-associated encephalopathy. Hydroxyethyl starch (HES, 130/0.4) is most widely used for volume replacement to maintain or improve tissue perfusion in patients with sepsis, trauma, and shock. This study was undertaken to investigate the effects of HES on BBB permeability, brain edema, inflammatory response and clinical outcome in septic rats. METHODS: Using the cecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with 15 ml/kg HES or normal saline 4h after the operation. Two hours later, expressions of brain toll-like receptor (TLR)-2, TLR4 and intercellular adhesion molecule (ICAM)-1 mRNA was determined by real-time reverse transcription-polymerase chain reaction; inflammatory cytokines like tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 by enzyme-linked immunosorbent assay; activity of nuclear factor-kappa B (NF-kappaB) by electrophoretic mobility shift assay; BBB permeability by Evans blue extravasation method; brain edema by wet/dry weight ratio. Weight loss, and clinical symptoms were also observed. RESULTS: Without obvious influence on systemic macrohemodynamics, HES could markedly attenuate BBB dysfunction and brain edema. Meanwhile, HES could significantly reduce TNF-alpha, IL-6, and ICAM-1 mRNA, inhibit NF-kappaB activation, and down-regulate TLR2 and TLR4 expression in the brain. In addition, CLP-induced increase in weight loss, and clinical symptoms was not reduced after treatment with HES. CONCLUSIONS: HES could ameliorate BBB dysfunction and inflammation mediators by modulating brain TLR2 and TLR4 expression during sepsis. However, HES could not improve clinical outcome.