Warfarin is the most commonly used oral anticoagulant drug in clinical practice due to its effective anticoagulant effect and low cost. Warfarin plays a crucial role in the anticoagulant treatment of patients with thrombotic diseases such as atrial fibrillation, heart valve replacement, and deep vein thrombosis. In general, low-dose warfarin can effectively achieve the optimal international normalized ratio (INR) for patients requiring anticoagulation therapy. In some cases, patients may require significantly higher doses of warfarin to achieve an INR in the desired range; failure to achieve this is commonly referred to as warfarin resistance. We report a rare case of cerebral infarction caused by atrial fibrillation and warfarin resistance in China. A Chinese patient with atrial fibrillation complicated by cerebral infarction had been taking warfarin for 2 years, and the dose was gradually increased to 12.5 mg per day; however, the INR remained below the standard. The patient was considered to be resistant to warfarin. The cause of warfarin resistance in this patient is unknown, but we speculate that pharmacodynamic and genetic factors may be involved. Finally, we chose to replace warfarin with rivaroxaban to avoid the risk of bleeding at high doses. To date, there has been no bleeding or infarcts since the patient was discharged. In cases where the cause of warfarin resistance cannot be determined, alternative drugs may be more appropriate. When considering warfarin resistance, it is important to actively search for the cause of resistance early on. If the cause is determined, appropriate measures should be taken. If the cause is not determined or cannot be resolved, the dose can be gradually increased under close monitoring, alternatives can be actively adopted, and patients can be informed and educated.

Objective This study compared ocular and cervical vestibular evoked myogenic potentials (oVEMP and cVEMP) among individuals with Parkinson's disease (PD) without dizziness, with nonspecific dizziness (dizziness without orthostatic hypotension), or with dizziness combined with orthostatic hypotension. Materials and methods We prospectively analyzed 30 of each of the three types of individuals who were admitted to Yongchuan Hospital of Chongqing Medical University (Chongqing, China) between June 2022 and April 2023. The three groups received oVEMP and cVEMP measurements using an electromyography-evoked potential system. For oVEMP, the N10 latency, P16 latency, and amplitude were compared between the three groups and the reference values. For cVEMP, the P13 latency, N23 latency, and amplitude were compared between the three groups and the reference values. Overall characteristics of oVEMP and cVEMP were also assessed using a previously published scoring scale originally developed for individuals with multiple sclerosis between the three groups included. The correlation between VEMP parameters (the latency and amplitude) and VEMP scores were simultaneously analyzed using Pearson’s bivariate correlation analysis. Results When compared with reference values, the oVEMP and cVEMP parameters of all three groups were found to be slightly different from the reference values. When the three groups included were compared with each other, in terms of oVEMP, the average amplitude in the left eye was significantly higher in those with nonspecific dizziness than in the other two groups. In terms of cVEMP, the average N23 latency on both the right and left sides of the neck and average amplitude on the right side of the neck were significantly higher in those with nonspecific dizziness than in the other two groups. Scores for oVEMP and cVEMP were also significantly higher for those with nonspecific dizziness than for the other two groups. There were no significant differences in oVEMP and cVEMP parameters, and scores for oVEMP and cVEMP between patients with dizziness combined with orthostatic hypotension and those without dizziness. In terms of correlation analysis, the N23 latency of left neck (r = 0.509, p < 0.001), the N23 latency of right neck (r = 0.495, p < 0.001), and the amplitude of right neck (r = 0.304, p = 0.004) correlated positively with cVEMP score. Conclusions Patients with PD without dizziness, with dizziness attributable to orthostatic hypotension, and with nonspecific dizziness may be all associated with vestibular dysfunction. The VEMP scores were highest in patients with nonspecific dizziness, so vestibular function is more severely affected in patients with nonspecific dizziness. The VEMP especially cVEMP may be useful for early diagnosis of nonspecific dizziness in PD.

Borna disease virus 1 (BoDV-1) is a neurotropic RNA virus that has been linked to fatal BoDV-1 encephalitis (BVE) in humans. Ferroptosis represents a newly recognized kind of programmed cell death that marked by iron overload and lipid peroxidation. Various viral infections are closely related to ferroptosis. However, the link between BoDV-1 infection and ferroptosis, as well as its role in BVE pathogenesis, remains inadequately understood. Herein, we used primary rat cortical neurons, human microglial HMC3 cells, and Sprague‒Dawley rats as models. BoDV-1 infection induced ferroptosis, as ferroptosis characteristics were detected (iron overload, reactive oxygen species buildup, decreased antioxidant capacity, lipid peroxidation, and mitochondrial damage). Analysis via qRT-PCR and Western blot demonstrated that BoDV-1-induced ferroptosis was mediated through Nrf2/HO-1/SLC7a11/GPX4 antioxidant pathway suppression. Nrf2 downregulation was due to BoDV-1 infection promoting Nrf2 ubiquitination and degradation. Following BoDV-1-induced ferroptosis, the PTGS2/PGE2 signaling pathway was activated, and various intracellular lipid peroxidation products and damage-associated molecular patterns were released, contributing to BVE occurrence and progression. More importantly, inhibiting ferroptosis or the ubiquitin‒proteasome system effectively alleviated BVE. Collectively, these findings demonstrate the interaction between BoDV-1 infection and ferroptosis and reveal BoDV-1-induced ferroptosis as an underlying pathogenic mechanism of BVE.

Objective: The aim of this study is to investigate the predictive value of relative surface area of hematoma on poor prognosis of spontaneous intracerebral hemorrhage (sICH). Materials and Methods: We retrospectively analyzed 102 patients with sICH who met the inclusion criteria, attending to Yongchuan Hospital of Chongqing Medical University from January 2019 to September 2020. Cranial CT within 6 h of onset was completed and repeated in 24 h. The volume and surface area of the hematoma are measured by software, and the relative surface area is calculated from the above data. The primary outcome was 90-day modified Rankin Scale (mRS) score, which was classified as good prognosis (<= 2 points) and poor prognosis (>2 points) according to the results. Univariate analysis and binary logistic regression analysis were used to calculate the effect of each variable on poor prognosis. Results: The study is comprised of 52 patients with favorable functional prognosis and 50 patients with unfavorable one. The findings showed that admission National Institutes of Health Stroke Scale(NIHSS), hematoma volume, relative surface area, hematoma expansion(HE) and serum calcium concentration were independent influencing factors for poor prognosis(P=0.004,0.007,0.023,0.001,0.035, respectively). ROC curve analysis revealed that the area under the curve of the relative surface area of the hematoma predicted poor prognosis was 0.894(95% CI 0.830-0.985, P <0.001), which was better than the rest of the variables. Conclusions: The relative surface area of hematoma in sICH is an independent risk factor for poor prognosis with a high predictive value, and large relative surface area suggests poor prognosis.

OBJECTIVE:To evaluate the prognostic value of the buffer coefficient, calculated as the ratio of the buffer volume (volume of intracranial cerebrospinal fluid) at the peak of brain edema to the baseline brain volume, and some other parameters in patients with massive cerebral infarction (MCI).METHODS:The cohort comprised 161 patients with MCI who were divided into good and poor prognosis groups according to modified Rankin Scale score at 90 days after onset. Differences in clinical and imaging parameters between these groups were analyzed by univariate analysis, and multifactorial binary logistic regression analysis was used to further identify influencing factors that were significantly different. Receiver operating characteristic curve was used to evaluate the diagnostic performance between the buffer volume and the buffer coefficient.RESULTS:The findings showed that a history of atrial fibrillation, intravenous tissue-type plasminogen activator administration, successful reperfusion, successful craniectomy, low-density lesion volume, brain volume, buffer volume, and buffer coefficient were significantly different between the poor and good prognosis groups (P < 0.05 for all comparisons). Multifactorial binary logistic regression analyses revealed that patients who had large low-density lesion volume and patients who had not achieved successful reperfusion or received intravenous tissue-type plasminogen activator were likely to have a poor prognosis (P < 0.05). The buffer coefficient was identified as an independent predictive factor for MCI (P < 0.001). The area under the receiver operating characteristic curve for the buffer coefficient was 0.862. When the cutoff value was 9.3%, sensitivity of predicting poor prognosis of patients with MCI was 94.7%.CONCLUSIONS:The buffer coefficient has potential benefits as a prognostic indicator for MCI that can be used to detect even subtle changes in brain edema.

ObjectivesThis study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients.MethodsAll patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer–Lemeshow goodness-of-fit method.ResultsThe SON2A2 score (0 to 8 points) consisted of history of smoking (no = 1, yes = 0, β = 0.81), onset-to-needle time (≥3.5 = 1,<3.5=0, β = 0.74), NIH Stroke Scale on admission (>10 = 2, ≤10 = 0, β = 1.22), neutrophil percentage (≥80.0% = 1, <80% = 0, β = 0.81), ASPECT score (≤11 = 2, >11 = 0, β = 1.30), and age (>65 years = 1, ≤65 years = 0, β = 0.89). The SON2A2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675–2.34) and poor outcomes (OR 1.89; 95%CI 1.68–2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77–0.86). Similar results were obtained in the validation cohort. The Hosmer–Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close.ConclusionThe SON2A2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients.

Previous studies suggest that in people with major depressive disorder (MDD), there exists a perturbation of the normal balance between the excitatory and inhibitory neurotransmitter systems in the visual cortex, indicating the possibility of altered visual cortical excitability. However, investigations into the neural activities of the visual cortex in MDD patients yielded inconsistent findings. The present study aimed to evaluate the visual cortical excitability utilizing a paired-pulse stimulation paradigm in patients with MDD and to access the paired-pulse behavior of recording visual evoked potentials (VEPs) as a marker of MDD. We analyzed the amplitudes of VEPs and paired-pulse suppression (PPS) at four different stimulus onset asynchronies (SOAs) spanning 93 ms to 133 ms. Further, the relationship between PPS and the symptom severity of depression was investigated using Spearman's correlation. We found that, whereas the first VEP amplitude remained unchanged, the second VEP amplitude was significantly higher in the MDD group compared to the healthy controls. As a result, the amplitude ratio (second VEP amplitude/first VEP amplitude) increased, indicating reduced PPS and thus increased excitability in the visual cortex. Moreover, we found the amplitude ratios had a significantly positive correlation with the symptom severity of depression in MDD, indicating a clinically useful biomarker for MDD. Our findings provide new insights into the changes in the excitation-inhibition balance of visual cortex in MDD, which could pave the way for specific clinical interventions.