METTL3-mediated ANXA2 inhibition confers neuroprotection in ischemic stroke: Evidence from in vivo and in vitro studies.

Given the important role of m6A, the most common and reversible mRNA modification, in the pathogenesis of ischemic stroke, this study investigates the mechanisms of m6A methyltransferase METTL3 in neuronal damage in ischemic stroke. In silico analysis was used to pinpoint the expression of ANXA2, which was verified in clinical peripheral blood samples. SD rats were used for middle cerebral artery occlusion (MCAO) establishment. The experimental data suggested that T lymphocytes were increased in peripheral blood samples of ischemic stroke patients and MCAO rats. The MCAO rats were treated with anti-ANXA2 alone or combined with RP101075 (T lymphocyte infiltration inhibitor), followed by brain injury assessment. Oxygen-glucose deprivation/reoxygenation (OGD/R) was induced in primary cortical neurons, where shRNAs targeting ANXA2 or METTL3, or overexpression plasmids of METTL3 were introduced to verify the regulatory function for METTL3. Inhibition of T lymphocyte migration to the ischemic brain reduced brain injury in MCAO rats and neuronal damage in OGD/R-exposed neurons. Ablation of ANXA2 in T lymphocytes inhibited the migration of T lymphocytes to the ischemic brain and reduced neuronal damage. Mechanistically, METTL3 reduced ANXA2 expression in T lymphocytes through m6A modification and inhibited p38MAPK/MMP-9 pathway activation, exerting protective effects against neuronal damage in ischemic stroke. Overall, this study reveals the neuroprotective effects of METTL3-mediated ANXA2/p38MAPK/MMP-9 inhibition against ischemic stroke.

Incidence and risk factors of postoperative delirium after pancreatic cancer surgery: a retrospective study.

PURPOSE: Postoperative delirium (POD) commonly occurs after major abdominal surgery and is associated with increased morbidity and mortality. There have been many studies on the relationship between POD and various surgeries, but research on POD after pancreatic cancer surgery is limited. The aim of this study was to identify the incidence and risk factors of POD after pancreatic cancer surgery. METHODS: The subjects of this retrospective analysis were 196 patients who were transferred for postoperative care after pancreatic cancer surgery, to a 12-bed critical care medicine ward at Shandong Provincial Hospital, affiliated with Shandong First Medical University, between January 2015 and December 2019. The patients were divided according to whether they suffered POD into a delirium group and a non-delirium group. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit and two independent medical practitioners analyzed all the data. Univariate and multiple logistic regression analyses were performed. RESULTS: The overall delirium incidence was 20.41%, which increased to 29.03% for patients aged ≥ 70 years. POD was associated with age, smoking, the American Society of Anesthesiologists classification, the Acute Physiology and Chronic Health Evaluation II score, and the TNM stage of the cancer. The variables concerning sex, drinking, hypertension, a history of cerebral disease, surgery type, operation time, amount of bleeding, and the intraoperative use of dexmedetomidine did not differ significantly between the two groups. There was no significant difference in the length of ICU stay, with the exclusion of long-term stay for complications, between the groups, but POD tended to prolong the postoperative hospital stay and increase the risk of mortality. There was also a gradual decline in the incidence of POD between 2015 and 2019, especially from 2015 to 2018, after preventive measures were implemented. CONCLUSION: POD is related to many risk factors and worthy of attention. Appropriate management can reduce its incidence or at least shorten its duration.

A multicenter prospective cohort study of cardiac ultrasound phenotypes in patients with sepsis: Study protocol for a multicenter prospective cohort trial.

Background: Sepsis-induced cardiomyopathy significantly increased the mortality of patients with sepsis. The diagnostic criteria for septic cardiomyopathy has not been unified, which brings serious difficulties to clinical treatment. This study aimed to provide evidence for the early identification and intervention in patients with sepsis by clarifying the relationship between the ultrasound phenotype of septic cardiomyopathy and the prognosis of patients with sepsis. Methods: This was a multicenter, prospective cohort study. The study population will consist of all eligible consecutive patients with sepsis or septic shock who meet the Sepsis 3.0 diagnostic criteria and were aged ≥18 years. Clinical data and echocardiographic measurements will be recorded within 2 h, at the 24th hour, at the 72nd hour, and on the 7th day after admission. The prevalence of each phenotype will be described as well, and their association with prognosis will be analyzed statistically. Discussion: To achieve early recognition, prevent reinjury, achieve precise treatment, and reduce mortality in patients with sepsis, it is important to identify septic cardiac alterations and classify the phenotypes at all stages of sepsis. First, there is a lack of studies on the prevalence of each phenotype in Chinese populations. Second, each phenotype and its corresponding prognosis are not clear. In addition, the prognosis of patients with normal cardiac ultrasound phenotypes vs. those with suppressed or hyperdynamic cardiac phenotypes is unclear. Finally, this study was designed to collect data at four specific timing, then the timing of occurrence, duration, changes over time, impact to outcomes of each phenotype will probably be found. This study is expected to establish a standard and objective method to assess the ultrasound phenotype of septic cardiomyopathy due to its advantages of visualization, non-invasiveness and reproducibility, and to provide more precise information for the hemodynamic management of septic patients. In addition, this research will promote the clinical application of critical care ultrasound, which will play an important role in medical education and make ultrasound the best method to assess cardiac changes in sepsis. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05161104, identifier NCT05161104.

Early initiation renal replacement therapy for fluid management to reduce central venous pressure is more conducive to renal function recovery in patients with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients' kidney function recovery. METHODS: A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients' renal function recovery at discharge, fluid balance, and levels of CVP were assessed. RESULTS: A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI. CONCLUSION: Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.