Identifying the Phenotypes of Sepsis that will Benefit from Red Blood Cell Transfusion Using Unsupervised Cluster Analysis.

BACKGROUND: Sepsis is a heterogeneous syndrome. Previous studies have shown controversial results of the effects of red blood cell transfusion (RBC) on the clinical outcomes of septic patients. This study aimed to identify the phenotypes of sepsis that will benefit from RBC transfusion. METHODS: Clinical data were extracted from the Medical Information Mart for Intensive Care III database. The study population included adult (age ≥ 18 years) septic patients with moderate non-bleeding anemia (hemoglobin ≤ 10 g/dL) within 24 hours after admission to the intensive care unit (ICU) between 2001 and 2012. After data preprocessing, partitioning around medoids function was used for unsupervised cluster analysis. We used Kaplan-Meier survival analysis and multivariable Cox proportional hazard models to explore the relationship between RBC transfusion and mortality. RESULTS: In total, 6,821 septic patients with moderate non-bleeding anemia within 24 hours after ICU admission, and 3,874 patients (56.8%) received RBC transfusion during their stay in the ICU. Using unsupervised cluster analysis, we identified three phenotypes of septic patients with moderate non-bleeding anemia: cluster A (n = 1,835) was characterized by advanced age and heart issues; cluster B (n = 3,043) was characterized by mild disease and relatively high hemoglobin levels; and cluster C (n = 1,943) was characterized by severe disease, low mean arterial pressure, bloodstream infection, coagulopathy, high lactate levels, and high mortality. Only for patients in cluster C, RBC transfusion exhibited protective effects in terms of the 14-day [hazard ratio (HR), 0.50; 95% confidence interval (CI), 0.41 - 0.61; p < 0.001], 28-day (HR, 0.61; 95% CI, 0.51 - 0.72; p < 0.001), and 90-day (HR, 0.67; 95% CI, 0.58 - 0.78; p < 0.001) mortality after adjusting the confounding variables. CONCLUSIONS: Utilizing unsupervised cluster analysis, we identified three phenotypes of septic patients with moderate non-bleeding anemia who had different responses to RBC transfusion. In the future, randomized controlled trials about prognostic outcomes of RBC transfusions can focus on the specific phenotype of sepsis.

Long non-coding RNA myocardial infarction-associated transcript promotes 1-Methyl-4-phenylpyridinium ion-induced neuronal inflammation and oxidative stress in Parkinson's disease through regulating microRNA-221-3p/ transforming growth factor /nuclear factor E2-related factor 2 axis.

This study attempted to evaluate the role of long non-coding RNA myocardial infarction-associated transcript (LncRNA MIAT) in Parkinson's disease (PD). The mouse model was established through intraperitoneal injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and in vitro model was induced by administrating cell with 1-Methyl-4-phenylpyridinium ion (MPP+). Rotarod test was conducted to evaluate the motor coordination of PD mice. In order to investigate the roles of LncRNA MIAT in neuronal inflammation and oxidative stress, MIAT shRNA (shMIAT) was transfected into MPP+-treated cells, and cell viability, cell apoptosis and oxidative stress response were evaluated. To evaluate the interactions between LncRNA MIAT and microRNA-221-3p (miR-221-3p)/TGF-ß1/Nrf2, miR-221-3p mimic, miR-221-3p inhibitor, NC-inhibitor and transforming growth factor-ß1 shRNA (shTGF-ß1) were subsequently transfected into MPP+-treated cells. Dual-luciferase reporter gene assays were performed to determine the interaction of miR-221-3p with MIAT or TGFB receptor 1 (TGFBR1). The expressions of LncRNA MIAT, miR-221-3p, TGFBR1, transforming growth factor (TGF-ß1) and nuclear factor E2-related factor 2 (Nrf2) were measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and immunoblotting. As a result, LncRNA MIAT was abundantly expressed in PD mice and cells, while downregulation of LncRNA MIAT promoted the survival of neurons, inhibited apoptosis and oxidative stress in neurons. LncRNA MIAT bound to miR-221-3p, and there was a negative correlation between miR-221-3p and LncRNA MIAT expression. In addition, miR-221-3p targeted TGFBR1 and suppressed TGF-ß1 expression but increased Nrf2 expression. LncRNA MIAT promoted MPP+-induced neuronal injury in PD via regulating TGF-ß1/Nrf2 axis through binding with miR-221-3p.

Quantitatively monitoring acute ischemic stroke patients post recombinant tissue plasminogen activator treatment.

BACKGROUND AND AIMS: Thrombolytic therapy is widely used to treat acute ischemic stroke (AIS) patients. As intracerebral hemorrhage is a life-threatening complication of this therapy, monitoring the fibrinolytic and coagulation systems is imperative. However, existing studies on plasmin inhibitor complex (PIC) and thrombin-antithrombin III complex (TAT) mostly apply the enzyme-linked immunosorbent assay (ELISA) method. The aim of this study is to establish the baseline of thrombolytic treatment for AIS patients; to monitor the fibrinolytic and coagulation system following alteplase administration; to ascertain the proper time point to predict intracerebral hemorrhage. METHODS: The method used to assess a patient's intravascular situation, namely chemiluminescence, was used to quantitatively assess the PIC, TAT, and thrombomodulin (TM). Immuno-turbidimetric was used to assess the concentration of D-dimer, fibrin/fibrinogen degradation products (FDP), and the Von Willebrand factor (vWF). The Clauss clotting method was used to assay the activated partial thromboplastin time (APTT), prothrombin time (PT) and FIB. RESULTS: PIC increased to its peak concentration at 3 hours post intravenous (IV) alteplase infusion and decreased by nearly 50% every 3 hours thereafter. After 24 hours, PIC returned to its normal range, while D-dimer and FDP decreased 3 hours later compared to PIC. PT and APTT exhibited no obvious change during the 24-hour period. TM also exhibited no changes during the treatment. CONCLUSION: PIC decreased 3 hours earlier than D-dimer and FDP. The combined test of PIC, D-dimer, and fibrinogen can be used to monitor the fibrinolytic system after the IV alteplase infusion. The use of IV alteplase had no impact on the endothelium. Creating a patient's individual data curve could assist in the prediction of hemorrhagic transformation (HT) and a stroke occurring.

HOTAIR drives autophagy in midbrain dopaminergic neurons in the substantia nigra compacta in a mouse model of Parkinson's disease by elevating NPTX2 via miR-221-3p binding.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell loss, largely confined to mesencephalic dopamine neurons of the substantia nigra. This study investigated the functional relevance of the HOX transcript antisense intergenic RNA (HOTAIR)/microRNA-221-3 (miR-221-3p)/neuronal pentraxin II (NPTX2) axis in the process of dopaminergic neuron autophagy using PD mouse models. The PD mouse models were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP), while PD cell model was constructed by pretreatment with 1-methyl-4-phenylpyridinium (MPP+). The expression of HOTAIR was then examined using RT-qPCR. In addition, the interactions between HOTAIR, miR-221-3p, and NPTX2 were detected through RIP and dual-luciferase reporter gene assays. CCK-8 assay was performed to measure cell viability, and the expression of autophagy-related genes was determined using Western blot analysis. HOTAIR was found to be significantly expressed in the substantia nigra compact tissues and MN9D cells following PD modeling. HOTAIR could bind to miR-221-3p and elevate the NPTX2 expression, which resulted in diminished cell viability and enhanced autophagy of dopaminergic neurons both in vitro and in vivo. In summary, down-regulation of HOTAIR could potentially inhibit the autophagy of dopaminergic neurons in the substantia nigra compacta in a mouse model of PD, thus saving the demise of dopaminergic neurons.