An analysis of clinical characteristics of rare bilateral medial medullary infarction: An observational study.

This study aimed to characterize the risk factors, etiology, clinical manifestations, anatomical characteristics, stroke mechanisms, imaging features, and prognosis of bilateral medial medullary infarction (BMMI). A retrospective analysis was conducted on 11 patients with BMMI who met the inclusion criteria at the Affiliated Hospital of Xuzhou Medical University from January 2013 to January 2023. The patients' imaging and clinical features were analyzed and summarized. Eleven patients (7 male, 4 female), aged 46 to 62 years, met the inclusion criteria. Common clinical presentations included dysarthria (90.9%), dysphagia (90.9%), quadriplegia (81.8%), and so on. Within 72 hours of onset, 8 cases presented with quadriplegia, 2 cases with hemiplegia, and 1 case without limb paralysis. The main risk factor for BMMI was hypertension, followed by diabetes. "Heart appearance" infarcts occurred in 4 cases (36.4%), while "Y appearance" infarcts occurred in 7 cases (63.6%). Among the patients, 3 had unilateral vertebral artery stenosis or occlusion, 5 had bilateral vertebral artery stenosis or occlusion, 2 had normal vertebral basilar artery, and 1 did not undergo cerebrovascular examination. All patients received standardized treatment for cerebral infarction. The prognosis was poor, with 81.8% of patients having an unfavorable outcome, including 1 death, 9 cases of disability, and only 1 patient achieving self-care ability after recovery. BMMI is more prevalent in males aged 45 to 60 years. The main risk factors are hypertension and diabetes. Atherosclerosis is the primary etiological subtype. The main clinical manifestations are dyskinesia, dizziness, quadriplegia, and dysarthria. The prognosis of BMMI is poor. The specific imaging features of "heart appearance" or "Y appearance" infarcts aid in the diagnosis of BMMI.

Circular RNA PTP4A2 regulates microglial polarization through STAT3 to promote neuroinflammation in ischemic stroke.

OBJECTIVE: Microglial polarization plays a critical role in neuroinflammation and may be a potential therapeutic target for ischemic stroke. This study was to explore the role and underlying molecular mechanism of Circular RNA PTP4A2 (circPTP4A2) in microglial polarization after ischemic stroke. METHODS: C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO), while primary mouse microglia and BV2 microglial cells experienced oxygen glucose deprivation/reperfusion (OGD/R) to mimic ischemic conditions. CircPTP4A2 shRNA lentivirus and Colivelin were used to knock down circPTP4A2 and upregulate signal transducer and activator of transcription 3 (STAT3) phosphorylation, respectively. Microglial polarization was assessed using immunofluorescence staining and Western blot. RNA pull-down and RNA binding protein immunoprecipitation (RIP) were applied to detect the binding between circPTP4A2 and STAT3. RESULTS: The levels of circPTP4A2 were significantly increased in plasma and peri-infarct cortex in tMCAO mice. CircPTP4A2 knockdown reduced infarct volume, increased cortical cerebral blood flow (CBF), and attenuated neurological deficits. It also decreased pro-inflammatory factors levels in peri-infarct cortex and plasma, and increased anti-inflammatory factors concentrations 24 h post-stroke. In addition, circPTP4A2 knockdown suppressed M1 microglial polarization and promoted M2 microglial polarization in both tMCAO mice and OGD/R-induced BV2 microglial cells. Moreover, circPTP4A2 knockdown inhibited the phosphorylation of STAT3 induced by oxygen-glucose deprivation. In contrast, increased phosphorylation of STAT3 partly counteracted the effects of circPTP4A2 knockdown. RNA pull-down and RIP assays further certified the binding between circPTP4A2 and STAT3. CONCLUSION: These results revealed regulatory mechanisms of circPTP4A2 that stimulated neuroinflammation by driving STAT3-dependent microglial polarization in ischemic brain injury. CircPTP4A2 knockdown reduced cerebral ischemic injury and promoted microglial M2 polarization, which could be a novel therapeutic target for ischemic stroke.

Remote limb ischemic postconditioning inhibits microglia pyroptosis by modulating HGF after acute ischemia stroke.

The repetitive inflation-deflation of a blood pressure cuff on a limb is known as remote limb ischemic postconditioning (RIPostC). It prevents brain damage induced by acute ischemia stroke (AIS). Pyroptosis, executed by the pore-forming protein gasdermin D (GSDMD), is a type of regulated cell death triggered by proinflammatory signals. It contributes to the pathogenesis of ischemic brain injury. However, the effects of RIPostC on pyroptosis following AIS remain largely unknown. In our study, linear correlation analysis confirmed that serum GSDMD levels in AIS patients upon admission were positively correlated with NIHSS scores. RIPostC treatment significantly reduced GSDMD level compared with patients without RIPostC at 3 days post-treatment. Besides, middle cerebral artery occlusion (MCAO) surgery was performed on C57BL/6 male mice and RIPostC was induced immediately after MCAO. We found that RIPostC suppressed the activation of NLRP3 inflammasome to reduce the maturation of GSDMD, leading to decreased pyroptosis in microglia after AIS. Hepatocyte growth factor (HGF) was identified using the high throughput screening. Importantly, HGF siRNA, exogenous HGF, and ISG15 siRNA were used to reveal that HGF/ISG15 is a possible mechanism of RIPostC regulation in vivo and in vitro.

Effects of NGS-based PGT-a for idiopathic recurrent pregnancy loss and implantation failure: a retrospective cohort study.

To clarify the effect of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) combined with trophectoderm (TE) biopsy on the pregnancy outcomes of idiopathic recurrent pregnancy loss (iRPL) and idiopathic recurrent implantation failure (iRIF), we conducted a retrospective cohort study of 212 iRPL couples and 66 iRIF couples who underwent PGT-A or conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. The implantation rate (IR) per transfer (64.2%), clinical pregnancy rate (CPR) per transfer (57.5%), and live birth rate (LBR) per transfer (45%) of iRPL couples of the PGT-A treatment group were significantly higher (p < 0.05) than those of the conventional IVF/ICSI group (IR per transfer,38.2%; CPR per transfer,33.3%; LBR per transfer, 28.4%), whereas the pregnancy loss rate (PLR) per transfer was similar between the two groups. These effects were also significant (p < 0.05) in iRPL couples with advanced maternal age (AMA, ≥35 years), whereas no significant differences were found in clinical outcomes between the PGT-A and conventional IVF/ICSI groups in younger iRPL couples (<35 years). The cumulative clinical outcomes of iRPL couples were comparable between the PGT-A and conventional IVF/ICSI groups. No significant differences were found in any clinical outcomes between the PGT-A and conventional IVF/ICSI groups for young or AMA couples with iRIF. In conclusion, NGS-based PGT-A involving TE biopsy may be useful for iRPL women to shorten the time to pregnancy and reduce their physical and psychological burden, especially for iRPL women with AMA; however, couples with iRIF may not benefit from PGT-A treatment. Considering the small sample size of the iRIF group, further investigations with a larger sample size are needed to verify our findings.

Increased plasma levels of circPTP4A2 and circTLK2 are associated with stroke injury.

OBJECTIVE: Accumulating studies have shown that circulating circular RNAs (circRNAs) represent novel biomarkers for many human diseases. We investigated whether plasma circPTP4A2 and circTLK2 levels are associated with stroke severity, infarct volume, stroke etiology, and functional outcome in acute ischemic stroke (AIS) patients. METHODS: We applied quantitative real-time PCR (qPCR) to measure plasma circPTP4A2 and circTLK2 levels of 236 AIS patients within 72 h of symptoms onset and 136 healthy controls. We further assessed the National Institutes of Health Stroke Scale (NIHSS), infarct size, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and the 90-day modified Rankin scale (mRS) for each patient. RESULTS: At admission, plasma circPTP4A2 and circTLK2 levels in patients with moderate to severe stroke were significantly higher compared to those with mild stroke. Logistic regression and receiver-operating characteristic (ROC) curve analyses indicated that they might function as predictive biomarkers for moderate to severe stroke. We also observed a medium positive correlation between these two circRNAs and NIHSS. Plasma circPTP4A2 and circTLK2 levels were slight positively correlated with cerebral infarct volume only in anterior circulation infarction (ACI) patients. Levels of both circPTP4A2 and circTLK2 were closely related with large artery atherosclerosis (LAA) stroke. Moreover, changes within 7 days after admission in circPTP4A2 and circTLK2 were able to predict unfavorable clinical outcome 90 days after AIS. INTERPRETATION: These results demonstrate that plasma circPTP4A2 and circTLK2 strongly correlated with severity, subtypes and prognosis of AIS, and they could serve as promising biomarkers.