Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial.

BACKGROUND: Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. METHODS: This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b-3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 µg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. DISCUSSION: This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Pulmonary artery sarcoma: an unexpected settler in the right ventricular outflow tract.

Pulmonary artery sarcoma (PAS) is a sporadic malignant tumor that mainly originates from the pulmonary arteries. However, PAS may also involve the right ventricular outflow tract (RVOT) and lead to obstruction, syncope, or sudden death. Early diagnosis and complete surgical resection are essential to prolong survival and improve the quality of life of patients with PAS. Herein, we report a case of a young female patient admitted for pulmonary malignancy and acute pulmonary embolism. The patient had a mass in the RVOT, which was detected by transthoracic echocardiography. Computed tomography and magnetic resonance imaging revealed the invasion depth and extent of the lesions. Surgical resection improved hemodynamics, while pathological and immunohistochemical tests confirmed the diagnosis of a pulmonary artery sarcoma. Local recurrence was detected in the adjacent tissues about two months after the surgery. Given the potential risk of reoperation, the patient was suggested to undergo conservative treatment.

The Association of Insomnia with Depression and Anxiety Symptoms in Patients Undergoing Noncardiac Surgery.

OBJECTIVE: Insomnia is common in patients undergoing surgery. It can increase the rate of postoperative complications, interfere with patient recovery, and decrease hospital satisfaction. However, there are few studies on perioperative insomnia. This study was conducted to investigate the differences in the demographic, health status, and clinical characteristics of patients with and without insomnia postoperatively, and to identify the potential risk factors of insomnia. METHODS: There were 299 non-cardiac surgery patients, 165 females, and 134 males, with a mean age of 55 years, enrolled in the study. The Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), and Montreal Cognitive Assessment (MoCA) were administered to all the patients preoperatively. The Visual Analogue Scale (VAS) was used preoperatively, and at the end of the surgery, and then one day, two days, and three days after surgery. The PHQ-9, the GAD-7, and the ISI were repeated three days after surgery. Insomnia was diagnosed by the ISI as being a score of 8-28 (mild: 8-14; moderate-severe: 15-21; severe: 22-28). The patients were divided into group A (with insomnia, N=78) and group B (without insomnia, N=221) according to their ISI score three days after surgery. The general clinical data of the two groups were analyzed first, and then binary logistic regression analysis was conducted to assess the risk factors of insomnia. RESULTS: A total of 299 non-cardiac surgery patients with a mean age of 55 years were enrolled in the study. Of the included patients, the number of females was 165 and the number of the male was 134. The incidence of insomnia at 3 days postoperatively was 26.1% (78/299). The average points that group A patients scored in the ISI, PHQ-9, and the GAD-7 were significantly higher than those in group B. The VAS score three days after surgery was significantly higher in group A. The PHQ-9 and the GAD-7 three days after surgery showed significantly higher depression and anxiety scores in group A. Logistic regression showed that the ISI (p<0.001, 95% CI=1.218-1.500) and the GAD-7 (p=0.003, 95% CI=1.041-1.218) preoperatively, and the PHQ-9 postoperatively (p<0.001, 95% CI=1.226-1.555), were risk factors of insomnia. CONCLUSION: Insomnia is common and can worsen after surgery. The present study suggests that depression and anxiety are risk factors for insomnia after surgery. There is a need for further research and the development of strategies for depression and anxiety management to ensure better sleep quality for patients, which will be of significant benefit to their health. CLINICAL TRIAL REGISTRATION: The study was registered at clinical trial (NCT04027751); Trial registration: clinical trial, NCT04027751. Registered 22 July 2019; https://clinicaltrials.gov/ct2/show/NCT04027751?cond=NCT04027751&cntry=CN&draw=2&rank=1.

Cognitive Deficits and Clinical Symptoms with Hippocampal Subfields in First-Episode and Never-Treated Patients with Schizophrenia.

Memory dysfunction and associated hippocampal disturbances play crucial roles in cognitive impairment of schizophrenia. To examine the relationships between cognitive function and the hippocampal subfields (HSs) in first-episode never-treated (FENT) schizophrenia patients, the HSs were segmented in 39 FENT patients and 30 healthy controls using a state-of the-art automated algorithm. We found no significant differences in any HSs between the patients and controls. However, multivariate regression analysis showed that the left cornu ammonis 1 (CA1), left hippocampal tail, left presubiculum, and right molecular layer contributed 40% to the variance of the PANSS negative symptom score. After adjusting for sex, age, education, and intracranial volume, the partial correlation analysis showed that the volumes of left CA1, CA3, CA4, molecular layer, granule cell layer and both left and right subiculum were negatively correlated with the MATRICS consensus cognitive battery (MCCB) Hopkins Verbal Learning Test (HVLT). Multiple regression analysis showed that the left CA1 and CA3 hippocampal abnormalities contributed 66% to the variance of the HVLT. Our results suggest no detectable HS deficits were found in FENT schizophrenia patients. However, the HSs may be involved in the symptoms and cognitive deficits of schizophrenia patients in the early phase of their illness.

Interactive effect of MTHFR C677T polymorphism and sex on symptoms and cognitive functions in Chinese patients with chronic schizophrenia.

The etiology of schizophrenia is still unknown, and the MTHFR gene has been shown to be associated with SCZ. Previous studies have shown that patients with schizophrenia exhibit sex differences in symptoms and cognitive function. However, no study has been conducted to investigate the sex difference in the association between C677T polymorphism and symptoms and cognitive impairment in Chinese patients with schizophrenia. The C677T polymorphism was genotyped in 957 patients with schizophrenia and 576 controls. Patients were also rated on the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The results showed that there were significant differences in MTHFR C677T genotype and allele distributions between male patients and male controls (both p<0.05), while there was no significant difference between female patients and female controls (both p>0.05). Further analysis showed that there were significant sex differences in the association between C677T genotype and negative symptoms, immediate memory or attention index score in schizophrenia (p<0.05). This study suggests that the complex interactive effect between MTHFR C677T polymorphism and sex plays an important role in some clinical characteristics of patients with schizophrenia.

Sex differences in the association of body mass index with symptoms and cognitive deficits in Chinese patients with chronic schizophrenia.

Accumulating studies have revealed gender differences in many aspects of schizophrenia (SZ), including obesity and cognitive function. The relationship between obesity and cognitive impairment in SZ has been studied before; however, the results are inconsistent. This study was designed to examine the sex differences in the relationship between body mass index (BMI) and cognitive deficits in Chinese patients with chronic SZ, which have not been investigated yet. 176 chronic patients with SZ (male/female = 108/68) and 200 controls (male/female = 120/80) were enrolled to compare the sex differences in cognitive functions measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), BMI, and their associations. The clinical symptoms were evaluated using the positive and negative syndrome scales (PANSS). Our results showed that male patients had lower BMI and more negative symptoms but fewer positive symptoms than female patients (all p < 0.05). However, there was no significant sex difference in RBANS scores. In male patients, BMI was correlated with age of onset, PANSS general psychopathology, total score, negative symptom, together with RBANS language, visuospatial/construction, and attention. Further regression analysis showed that in male patients, BMI was significantly associated with RBANS language, PANSS general psychopathology, PANSS total score, and age of onset, with adjusted R2 = 0.22. These findings revealed significant sex differences in BMI, cognitive dysfunctions and their association in SZ. Nonetheless, these results should only be considered as preliminary because of the cross-sectional design, which will deserve further replication in first-episode patients using a prospective longitudinal design.

Obesity in Chinese patients with chronic schizophrenia: Prevalence, clinical correlates and relationship with cognitive deficits.

The prevalence of obesity in schizophrenia patients is high, especially in chronic and medicated patients. Few studies have explored the relationships between obesity, cognition and clinical correlates in patients with schizophrenia. This study was designed to assess the prevalence and clinical correlates of obesity and its relationship to cognitive impairment in Chinese patients with schizophrenia. We recruited 633 inpatients and collected clinical, demographic data and lipid parameters. The Positive and Negative Syndrome Scale (PANSS) and its five-factor model were adopted for psychopathological symptoms. The prevalence of comorbid obesity in schizophrenia patients was 16.4%. The plasma levels of glucose, triglyceride, low density lipoprotein (LDL), apolipoprotein B, and cholesterol were higher, but high density lipoprotein (HDL) levels were lower in obese patients than those in non-obese patients (all p < 0.05). Furthermore, obese patients had lower PANSS negative symptom, cognitive factor and total scores than non-obese patients (all p < 0.05). Correlation analysis showed a significant correlation between BMI and the following variables: age, marriage, gender, negative symptoms, general psychopathological symptoms, cognitive factor, PANSS total score, glucose, triglycerides, HDL, LDL, cholesterol and apolipoprotein B (all p < 0.05). Further multiple regression showed that PANSS cognitive factor, PANSS total score, and triglyceride were important independent predictors of obesity. Our results indicate a high prevalence of obesity in Chinese patients with chronic schizophrenia. Multiple demographics, clinical variables, and lipid parameters are associated with obesity in schizophrenia. Moreover, obesity appears to be a protective factor for psychological symptoms. However, not having objective assessments for cognition in this study is a limitation.

The Role of Long Noncoding RNAs in Central Nervous System and Neurodegenerative Diseases.

Long noncoding RNAs (lncRNAs) refer to a group of noncoding RNAs (ncRNAs) that has a transcript of more than 200 nucleotides in length in eukaryotic cells. The lncRNAs regulate gene expression at epigenetic, transcriptional, and post-transcriptional levels by multiple action modes. In this review, we describe the diverse roles reported for lncRNAs, and discuss how they could mechanistically be involved in the development of central nervous system (CNS) and neurodegenerative diseases. Further studies on the function of lncRNAs and their mechanism will help deepen our understanding of the development, function, and diseases of the CNS, and provide new ideas for the design and development of some therapeutic drugs.

Neuroprotective effect of ischemic postconditioning on sciatic nerve transection.

Ischemic preconditioning or postconditioning has been shown to have neuroprotective effect on cerebral ischemia, but it has not been studied in peripheral nerve injury. In this study, a rat model of sciatic nerve transection was established, and subjected to three cycles of ischemia for 10 minutes + reperfusion for 10 minutes, once a day. After ischemic postconditioning, serum insulin-like growth factor 1 expression increased; sciatic nerve Schwann cell myelination increased; sensory function and motor function were restored. These findings indicate that ischemic postconditioning can effectively protect injured sciatic nerve. The protective effect is possibly associated with upregulation of insulin-like growth factor 1.

Research progress on the roles of microRNAs in governing synaptic plasticity, learning and memory.

The importance of non-coding RNA involved in biological processes has become apparent in recent years and the mechanism of transcriptional regulation has also been identified. MicroRNAs (miRNAs) represent a class of small regulatory non-coding RNAs of 22bp in length that mediate gene silencing by identifying specific sequences in the target messenger RNAs (mRNAs). Many miRNAs are highly expressed in the central nervous system in a spatially and temporally controlled manner in normal physiology, as well as in certain pathological conditions. There is growing evidence that a considerable number of specific miRNAs play important roles in synaptic plasticity, learning and memory function. In addition, the dysfunction of these molecules may also contribute to the etiology of several neurodegenerative diseases. Here we provide an overview of the current literatures, which support non-coding RNA-mediated gene function regulation represents an important but underappreciated, layer of epigenetic control that facilitates learning and memory functions.

MiR-7684-5p leads to surgery-induced cognitive decline in mice probably through the downregulation of SorLA.

BACKGROUND: Postoperative cognitive dysfunction is a postoperative severe complication caused by many factors. However, its specific pathogenesis remains unclear. MicroRNAs (miRNAs), which are involved in the pathogenesis of neurodegenerative diseases, may also affect POCD. METHODS: In this research, microarray technology was used to screen 26 miRNAs that had a differential expression in the hippocampus of mouse between the surgery group and control group. The qRT-PCR verification on the hippocampuses of 10 pairs of mouse testifies the high expression of miR-7684-5p in the surgery group (identical with the result of chip). RESULTS: Surgical trauma was found to induce the expression of miR-7684-5p with the accumulation of Aß in the hippocampus. Furthermore, miR-7684-5p knockdown effectively reduced the levels of Aß triggered by surgery, and attenuated hippocampal-dependent memory impairment. Moreover, we testify that sorLA is a target gene of miR-7684-5p through bioinformatics prediction and dual-luciferase report gene experiment. CONCLUSIONS: Our data indicate that decreased postoperative cognitive function may be caused by the increased generation of Aß by reducing sorLA expression. Our work implicates miR-7684-5p as a potential biomarker and a novel therapeutic target.