Risk Prediction Models for Invasive Mechanical Ventilation in Patients with Autoimmune Encephalitis: A Retrospective Cohort Study.

Methods: A multivariate predictive nomogram model was developed using the risk factors identified by LASSO regression and assessed by receiver operator characteristics (ROC) curve, calibration curve, and decision curve analysis. Results: The risk factors predictive of severe respiratory failure were male gender, impaired hepatic function, elevated intracranial pressure, and higher neuron-specific enolase. The final nomogram achieved an AUC of 0.770. After validation by bootstrapping, a concordance index of 0.748 was achieved. Conclusions: Our nomogram accurately predicted the risk of developing respiratory failure needing IMV in AE patients and provide clinicians with a simple and effective tool to guide treatment interventions in the AE patients.

TREM2 improves neurological dysfunction and attenuates neuroinflammation, TLR signaling and neuronal apoptosis in the acute phase of intracerebral hemorrhage.

Neuroinflammation contributes to secondary brain injury following intracerebral hemorrhage (ICH). Triggering receptor expressed on myeloid cells 2 (TREM2) confers strong neuroprotective effect by suppressing neuroinflammatory response in experimental ischemic stroke. This study aimed to clarify the neuroprotective role of TREM2 and potential underlying mechanism in a mouse model of ICH and in vitro. Adeno-associated virus (AAV) and green fluorescent protein-lentivirus (GFP-LV) strategies were employed to enhance TREM2 expression in the C57/BL6 mice and BV2 cells, respectively. The adult male C57/BL6 mice were subjected to ICH by administration of collagenase-IV in 1 month after the AAV particles injection. An in vitro ICH model was performed with oxygen hemoglobin in BV2 cells. Toll-like receptor 4 (TLR4) antagonist TAK242 was applied at 6 h following ICH. Neurological function, TREM2, pro-inflammatory cytokines, brain water content and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were evaluated at 24 h following ICH. TLR4, NF-κB and mitogen-activated protein kinases (MAPK) signaling pathways were also determined by Western blot analysis at the same time point. The levels of TREM2 were increased at 12 h, peaked at 24 h and recovered on 7d following ICH. TREM2 overexpression ameliorated ICH induced neurological dysfunction, inhibited neuroinflammation, and attenuated apoptosis and brain edema. Further mechanistic study revealed that TREM2 overexpression inhibited TLR4 activation and NF-κB and MAPK signaling pathways. ICH increased the percentage of TUNEL-positive cells, which was markedly decreased by TREM2 overexpression. A similar improvement was also observed by the administration of TAK242 following ICH. TREM2 improves neurological dysfunction and attenuates neuroinflammation and neuronal apoptosis in the acute phase of ICH, which is, at least in part, mediated by negatively regulating TLR4 signaling pathway. These findings highlight TREM2 as a potential target for early brain injury following ICH.

4R-cembranoid protects neuronal cells from oxygen-glucose deprivation by modulating microglial cell activation.

As major immune responsive cells in the central nervous system (CNS), activated microglia can present pro-inflammatory M1 phenotype aggravating the neuronal injury or anti-inflammatory M2 phenotype providing neuroprotection and promoting neuronal survival in neurodegenerative diseases. In this study, we demonstrated that a compound, 4R-cembranoid (4R, 1S, 2E, 4R, 6R,-7E, 11E-2, 7, 11-cembratriene-4, 6-diol cembranoids) promoted M2 phenotype while attenuated M1 phenotype in N9 cells, a microglial cell line. Following Lipopolysaccharides (LPS) or Oxygen-glucose deprivation (OGD) treatment, the N9 cells treated by 1 µM 4R showed an increased Arginase-1 (Arg1, a M2 marker) expression and a reduced inducible nitric oxide synthase (iNOS, M1 marker) expression. In addition, the conditioned medium of 4R-treated post-OGD N9 cells protected neuro2a cells, a neuronal cell line, from OGD-induced injury. The viability of neuro2a cells in OGD condition was increased by 54.5% after treated with the conditioned medium of 4R-treated post-OGD N9 cells. Furthermore, we demonstrated the protective mechanism of 4R was associated with a decreased TNF-α release and an increased IL-10 release from N9 cells. In conclusion, our study demonstrated that the neuroprotective effects of 4R were through the regulation of microglial activation by promoting the protective M2 activation and inhibiting the damaging M1 activation. Therefore, the findings of this study suggest that 4R could be a promising lead structure for the development of drugs for the treatment of ischemic stroke and other neurodegenerative diseases with an inflammatory component involved.

Association of clopidogrel high on-treatment reactivity with clinical outcomes and gene polymorphism in acute ischemic stroke patients: An observational study.

High on-treatment platelet reactivity (HTPR) was suggested to be better correlated with recurrent ischemic events as compared with gene polymorphism, whereas most of the results were from white populations with acute coronary disease. The evidence is relatively limited regarding HTPR and its genetic determinants in predicting clinical outcomes of stroke among Chinese-Han patients.A prospective study including 131 Chinese-Han stroke patients treated with clopidogrel was analyzed. Platelet function was assessed by light transmission aggregometry (LTA)- adenosine diphosphate (ADP) method. HTPR was defined as 5 µM ADP induced platelet aggregation > 46%. CYP2C19 and P2Y12 genotype were detected using the PCR-RFLP method. The difference in the occurrence of the primary endpoint was analyzed according to platelet function and genetic status.Sixty-three (48.1%) subjects displayed HTPR after administering clopidogrel for 1 week. The prevalence of HTPR was significantly higher in CYP2C19 loss-of-function (LOF) alleles (2, 3) carriers vs wild-type homozygotes (71.7% vs 32.1%, P < .01), and logistic regression analysis showed that carriers of CYP2C19 LOF alleles were an independent risk factor of HTPR. Survival analysis indicated that patients with HTPR had an increased risk of primary endpoints (20.6% vs 7.3%, P = .04), whereas the presence of CYP2C19 LOF alleles or P2Y12 H2 haplotype did not increase the incidence of ischemic events. Cox regression analysis demonstrated that HTPR was an independent predictor of the primary composite endpoint (HR, 3.1; 95% CI, 1.07-8.99; P = .04).We identified a high prevalence of clopidogrel-HTPR in a cohort of Chinese-Han patients with acute ischemic stroke, and patients with HTPR may have an increased risk of recurrent ischemic stroke events. CYP2C19 LOF alleles are associated with HTPR but not with stroke prognosis. Further clinical trials with large samples are needed to confirm these findings.

Intra- and Interrater Reliability of Infrared Image Analysis of Facial Acupoints in Individuals with Facial Paralysis.

Infrared thermography (IRT), as a noncontact tool for temperature measurement, is widely applied in the study of acupuncture modernization. The aim of this study was to assess the intra- and interrater reliability of infrared image analysis of facial acupoints of subjects with facial paralysis and determine the factors influencing the variability of the measured values. A total of 26 patients with facial paralysis on one side, aged 26 to 53 years, participated voluntarily in the study. Facial infrared thermal images of all participants were analyzed by two trained raters at two different time points at a one-week interval. The intraclass correlation coefficient (ICC) was used to determine the intra- and interrater reliability of IRT measurements. The ICC values varied depending on the analyzed acupoints. The reliability of temperature measurement ranged from moderate to excellent (intrarater, ICC ranged from 0.669 to 0.990; interrater, ICC ranged from 0.661 to 0.987). The reliability of temperature difference measurement ranged from low to excellent (intrarater, ICC ranged from 0.412 to 0.882; interrater, ICC ranged from 0.334 to 0.828). The main influencing factor of reliability is the incomplete consistency in selecting acupoint positions when repeatedly positioning the same acupoint manually. Despite low reliability of temperature difference measurement at some acupoints, some auxiliary measures can be used to reduce the error of manual positioning. Thus, infrared thermal imaging still has the potential to assist in objective and quantitative research on acupuncture.