Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.

BACKGROUND: Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), although the specific underlying mechanisms remain largely unknown. This study aimed to clarify the role and possible mechanism of acid sphingomyelinase (ASM)-mediated osteoblast ferroptosis in T2DOP. METHODS: We treated hFob1.19 cells with normal glucose (NG) and different concentrations of high glucose (HG, 26.25 mM, 35 mM, or 43.75 mM) for 48 h. We then measured cell viability and osteogenic function, quantified ferroptosis and autophagy levels, and measured the levels of ASM and ceramide in the cells. To further investigate the specific mechanism, we examined these indicators by knocking down ASM expression, hydroxychloroquine (HCQ) treatment, or N-acetylcysteine (NAC) treatment. Moreover, a T2DOP rat model was induced and microcomputed tomography was used to observe the bone microstructure. We also evaluated the serum levels of iron metabolism-associated factors, ceramide and lipid peroxidation (LPO) and measured the expression of ASM, LC3 and GPX4 in bone tissues. RESULTS: HG inhibited the viability and osteogenic function of osteoblasts by inducing ferroptosis in a concentration-dependent manner. Furthermore, the expression of ASM and ceramide and autophagy levels were increased by HG treatment, and these factors were required for the HG-induced reactive oxygen species (ROS) generation and LPO. Similarly, inhibiting intracellular ROS also reduced HG-induced ASM activation and autophagy. ASM-mediated activation of autophagy was crucial for HG-induced degradation of GPX4, and inhibiting ASM improved osteogenic function by decreasing HG-induced autophagy, GPX4 degradation, LPO and subsequent ferroptosis. We also found that inhibiting ASM could alleviated ferroptosis and autophagy and improved osteogenic function in a T2DOP rat model. CONCLUSION: ASM-mediated autophagy activation induces osteoblast ferroptosis under HG conditions through the degradation of GPX4, providing a novel mechanistic insight into the treatment and prevention of T2DOP.

Effect of glucocorticoid for patients with type A aortic dissection undergoing surgical repair with deep hypothermic circulatory arrest: A single-center, retrospective study.

BACKGROUND: Postoperative patients with Type A aortic dissection (TAAD) often experience severe inflammatory responses caused by multiple factors perioperatively. However, the effect of postoperative glucocorticoid (GC) use, which is a potent anti-inflammatory agent, on complications or all-cause mortality is unclear. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest between January 2020 and December 2021 were included in the study. Characteristics of patients treated with and without GCs were compared. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Propensity score matching was used to balance baseline differences between groups. Kaplan-Meier curves were used to compare survival probability. RESULTS: A total of 393 postoperative patients with TAAD were included in the study. Forty of them (10.2%) received GC treatment at a median daily methylprednisolone-equivalent dose of 0.6 mg/kg (0.4-0.7) for a median period of 2 (1-3) days. Patients on GCs had more intraoperative blood transfusions, higher postoperative APACHE II (12 vs 9, p = .004) and SOFA (9 vs 6, p < .001) scores, worse perioperative hepatic, renal and cardiac function. The in-hospital mortality in the matched cohort did not differ between groups [GC n = 11/40 (27.5%) versus Non-GC n = 19/80 (23.8%); p = .661]. CONCLUSIONS: The propensity to use GCs correlated with the critical status of the patient. However, low dose and short-term postoperative GC treatment did not reduce in-hospital mortality rates among patients with TAAD. A more appropriate regimen should be further investigated.

Poly(ADP-ribose) polymerase family member 14 promotes functional recovery after spinal cord injury through regulating microglia M1/M2 polarization via STAT1/6 pathway.

Poly(ADP-ribose)polymerase family member 14 (PARP14), which is an intracellular mono(ADP-ribosyl) transferase, has been reported to promote post-stroke functional recovery, but its role in spinal cord injury (SCI) remains unclear. To investigate this, a T10 spinal cord contusion model was established in C57BL/6 mice, and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression. We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury, accompanied by obvious neuronal apoptosis, severe neuroinflammation, and slight bone loss. Furthermore, PARP14 levels were elevated in microglia after SCI, PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia (anti-inflammatory phenotype) to M1-polarized microglia (pro-inflammatory phenotype) that may have been mediated by the signal transducers and activators of transcription (STAT) 1/6 pathway. Next, microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γ and interleukin-4, respectively. The results showed that PARP14 knockdown promoted microglia M1 polarization, accompanied by activation of the STAT1 pathway. In addition, PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway. In conclusion, these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.

The role of mechanosensor Piezo1 in bone homeostasis and mechanobiology.

Bones and articular cartilage are important load-bearing tissues. The fluid flow inside the bone cells and cell interaction with the extracellular matrix serve as the mechanical cues for bones and joints. Piezo1 is an ion channel found on the cell surface of many cell types, including osteocytes and chondrocytes. It is activated in response to mechanical stimulation, which subsequently mediates a variety of signaling pathways in osteoblasts, osteocytes, and chondrocytes. Piezo1 activation in osteoblastic cells positively regulates osteogenesis, while its activation in joints mediates cartilage degradation. This review focuses on the most recent research on Piezo1 in bone development and regeneration.

Early postoperative organ dysfunction is highly associated with the mortality risk of patients with type A aortic dissection.

OBJECTIVES: This study assessed the impact of early postoperative organ dysfunction (EPOD) on in-hospital mortality of patients with type A aortic dissection (TAAD) after surgery. METHODS: Patients with TAAD who underwent surgical repair requiring deep hypothermic circulatory arrest from January 2020 to December 2021 were included. The Sequential Organ Failure Assessment (SOFA) score was calculated for 3 days postoperatively to stratify the severity of organ dysfunction. Patients with the SOFA of 0-4, 5-8 or >8 were defined as mild, moderate or severe EPOD. The primary outcome was in-hospital mortality, and a composite secondary outcome was defined as in-hospital death or any major complications. Kaplan-Meier curves were used to compare survival probability. The area under the receiver operating characteristic curve and calibration plots were used to evaluate the predictive power and overall performance of SOFA. RESULTS: Of the 368 patients, 5 patients (3%) with moderate EPOD and 33 patients (23%) with severe EPOD died. No patient died with mild EPOD. The areas under the receiver operating characteristic curve of SOFA for predicting mortality and the composite outcome were 0.85 (0.81-0.88) and 0.81 (0.77-0.85) on postoperative day 1. Each point of postoperative day 1 SOFA score corresponded to an odds ratio of 1.65 (1.42-1.92) for mortality. Of the 6 components of the SOFA system, only coagulation (2.34 [1.32-4.13]), cardiovascular (1.47 [1.04-2.08]), central nervous system (1.96 [1.36-2.82]) and renal (1.67 [1.04-2.70]) functions were associated with the higher risk of mortality. CONCLUSIONS: EPOD stratified by the SOFA score was associated with a higher risk of death and predicted the clinical outcomes of patients with TAAD with good accuracy.

Different frequencies of repetitive transcranial magnetic stimulation combined with local injection of botulinum toxin type A for post-stroke lower limb spasticity: study protocol for a prospective, single-center, non-randomized, controlled clinical trial.

No definite consensus has currently been reached regarding the safety and efficacy of low- or high-frequency repetitive transcranial magnetic stimulation in the treatment of post-stroke muscle spasticity. The latest research indicates that when combined with local injections of botulinum toxin type A, it is more effective on post-stroke muscle spasticity than local injections of botulinum toxin type A alone. We designed a prospective, single-center, non-randomized, controlled clinical trial to investigate the safety and efficacy of different frequencies of repetitive transcranial magnetic stimulation combined with local injections of botulinum toxin type A in treating post-stroke lower limb muscle spasticity to determine an optimal therapeutic regimen. This trial will enroll 150 patients with post-stroke muscle spasticity admitted to the Department of Rehabilitation Medicine at the First Affiliated Hospital of China Medical University. All enrolled patients will undergo routine rehabilitation training and will be divided into five groups (n = 30 per group) according to the particular area of cerebral infarction and treatment methods. Group A: Patients with massive cerebral infarction will be given local injections of botulinum toxin type A and low-frequency (1 Hz) repetitive transcranial magnetic stimulation on the contralateral side; Group B: Patients with non-massive cerebral infarction will be given local injections of botulinum toxin type A and high-frequency (10-20 Hz) repetitive transcranial magnetic stimulation on the affected side; Group C: Patients with massive/non-massive cerebral infarction will be given local injections of botulinum toxin type A; Group D: Patients with massive cerebral infarction will be given low-frequency (1 Hz) repetitive transcranial magnetic stimulation on the contralateral side; and Group E: Patients with non-massive cerebral infarction will be given high-frequency (10-20 Hz) repetitive transcranial magnetic stimulation on the affected side. The primary outcome measure of this trial is a modified Ashworth scale score from 1 day before treatment to 12 months after treatment. Secondary outcome measures include Fugl-Meyer Assessment of Lower Extremity, Visual Analogue Scale, modified Barthel index, and Berg Balance Scale scores for the same time as specified for primary outcome measures. The safety indicator is the incidence of adverse events at 3-12 months after treatment. We hope to draw a definite conclusion on whether there are differences in the safety and efficacy of low- or high-frequency repetitive transcranial magnetic stimulation combined with botulinum toxin type A injections in the treatment of patients with post-stroke lower limb spasticity under strict grouping and standardized operation, thereby screening out the optimal therapeutic regimen. The study protocol was approved by the Medical Ethics Committee of the First Affiliated Hospital of China Medical University (approval No. [2021] 2021-333-3) on August 19, 2021. The trial was registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR2100052180) on October 21, 2021. The protocol version is 1.1.

Veno-Arterial Extracorporeal Membrane Oxygenation for Patients Undergoing Acute Type A Aortic Dissection Surgery: A Six-Year Experience.

Objectives: Acute type A aortic dissection (aTAAD) is usually lethal without emergency surgery. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in patients with cardiogenic shock following cardiac surgery, VA-ECMO support following aTAAD surgery has not been well-described. Based on our 6-year experience, we aimed to retrospectively analyze risk factors, application and timing of VA-ECMO, and outcomes in aTAAD patients. Methods: In this retrospective, single-center study, we enrolled adult patients who underwent aTAAD surgery from January 2014 to December 2019 and were supported with VA-ECMO. Patients were divided into two groups according to whether or not they were successfully weaned from VA-ECMO. Preoperative, intraoperative and postoperative variables were assessed and analyzed. Outcomes of the patients were followed up until discharge. Results: Twenty-seven patients who received aTAAD surgery with VA-ECMO support were included in the study. Nine patients (33.3%) were successfully weaned from VA-ECMO. The median VA-ECMO support time and length of hospital stay in the successfully weaned group were significantly longer than in the group could not be successfully weaned (192 [111-327] vs. 55 [23-95] h, p < 0.01; 29 [18-40] vs. 4 [3-8] days, p < 0.01). Overall in-hospital mortality was 81.5%. The main causes of death were bleeding (37%), neurological complications (15%), and multiple organ dysfunction syndrome (15%). Preoperative levels of creatine kinase-MB (CK-MB) were lower in patients who were successfully weaned from VA-ECMO than in the failed group (14 [6-30] vs. 55 [28-138] U/L, p < 0.01). Postoperative peak levels of CK-MB, cardiac troponin T, lactate dehydrogenase, and lactate were significantly lower in the successful group than in the failed group. Conclusion: Postoperative VA-ECMO support was rarely used in aTAAD patients. Our study showed that VA-ECMO can be considered as a salvage treatment in aTAAD patients, despite the high rate of complications and mortality.

Early risk stratification of acute type A aortic dissection: development and validation of a predictive score.

BACKGROUND: The performance of published preoperative risk scores for acute type A aortic dissection (aTAAD) is suboptimal. So, the predictive power of these scores were externally validated in order to develop and validate a more reliable preoperative score for identification of patients at high risk of mortality. METHODS: Potential preoperative risk variables of consecutively admitted patients with aTAAD were prospectively collected. Seven published risk scores were validated with our dataset. For derivation and internal validation, the original population was divided at a ratio of 7:3. Logistic regression was used to identify variables for the new score. A 50-patient retrospective dataset was used for external validation. The predictive accuracy for post-operative mortality was evaluated using the area under the receiver operating characteristic (AUROC) curve. RESULTS: During the study period, 225 patients with aTAAD were admitted preoperatively. Of these, 209 underwent surgical repair and 29 died postoperatively. The AUROCs of the seven published pre-operative risk scores for post-operative mortality ranged from 0.57 to 0.77. Four variables were derived for the new score system, i.e., Acute myocardial ischemia, Lactate, Iliac arteries involved, and CreatininE (the ALICE score). The AUROCs for post-operative mortality in the derivation, internal and external validation populations were 0.85, 0.88 and 0.83, respectively. At a cutoff value of 3, the ALICE score for post-operative mortality had a sensitivity of 71% to 88% and specificity of 78% to 86%. CONCLUSIONS: The ALICE score comprising four components might help bedside clinicians in early detection of the most severe aTAAD patients.

Effect of Sequential Noninvasive Ventilation on Early Extubation After Acute Type A Aortic Dissection.

BACKGROUND: Acute type A aortic dissection (aTAAD) is associated with a high incidence of prolonged postoperative invasive mechanical ventilation. We aimed to assess whether sequential noninvasive ventilation (NIV) could facilitate early extubation postoperatively after a spontaneous breathing trial (SBT) failure among aTAAD patients. METHODS: Beginning in December 2016, we transitioned our weaning strategy from repeated SBT until success (phase 1) to extubation concomitant with sequential NIV (phase 2) for subjects who failed their first SBT. The primary outcomes were re-intubation rate, duration of invasive ventilation, and total duration of ventilation. RESULTS: During the study period, 78 subjects with aTAAD failed their first postoperative SBT (38 subjects in phase 1 and 40 subjects in phase 2). Subjects extubated with sequential NIV had shorter median (interquartile range [IQR]) duration of invasive ventilation of 39.5 (30.8-57.8) h vs 89.5 (64-112) h (P < .001) and median (IQR) length of ICU stay of 6 (4.0-7.8) d vs 7.5 (5.8-9.0) d (P = .030). There were no significant differences between the 2 phases with regard to rates of re-intubation (7.5% vs 7.89%, P = .95), tracheostomy (2.5% vs 5.26%, P = .53), and in-hospital mortality (2.5% vs 2.63%, P = .97). CONCLUSIONS: Early extubation followed by sequential NIV significantly reduced duration of invasive ventilation and length of ICU stay without increasing re-intubation rate in postoperative subjects with aTAAD who failed their first SBT.

Research hotspots and effectiveness of repetitive transcranial magnetic stimulation in stroke rehabilitation.

Repetitive transcranial magnetic stimulation, as a relatively new type of rehabilitation treatment, is a painless and non-invasive method for altering brain excitability. Repetitive transcranial magnetic stimulation has been widely used in the neurorehabilitation of stroke patients. Here, we used CiteSpace software to visually analyze 315 studies concerning repetitive transcranial magnetic stimulation for stroke rehabilitation from 1999 to 2019, indexed by Web of Science, to clarify the research hotspots in different periods and characterize the gradual process of discovery in this field. We found that four main points were generally accepted: (1) repetitive transcranial magnetic stimulation has a positive effect on motor function recovery in patients with subcortical stroke; (2) it may be more advantageous for stroke patients to receive low-frequency repetitive transcranial magnetic stimulation in the unaffected hemispheres than to receive high-frequency repetitive transcranial magnetic stimulation in affected hemisphere; (3) low-frequency repetitive transcranial magnetic stimulation has become a potential therapeutic tool for patients with non-fluent aphasia after chronic stroke for neurological rehabilitation and language recovery; and (4) there are some limitations to these classic clinical studies, such as small sample size and low test efficiency. Our assessment indicates that prospective, multi-center, large-sample, randomized controlled clinical trials are still needed to further verify the effectiveness of various repetitive transcranial magnetic stimulation programs for the rehabilitation of stroke patients.

Exogenous brain-derived neurotrophic factor attenuates cognitive impairment induced by okadaic acid in a rat model of Alzheimer's disease.

Decreased expression of brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of Alzheimer's disease, and a typical pathological change in Alzheimer's disease is neurofibrillary tangles caused by hyperphosphorylation of tau. An in vivo model of Alzheimer's disease was developed by injecting okadaic acid (2 µL) and exogenous BDNF (2 µL) into the hippocampi of adult male Wister rats. Spatial learning and memory abilities were assessed using the Morris water maze. The expression levels of protein phosphatase 2A (PP2A), PP2Ac-Yp307, p-tau (Thr231), and p-tau (Ser396/404) were detected by western blot assay. The expression levels of BDNF, TrkB, and synaptophysin mRNA were measured by quantitative real-time polymerase chain reaction. Our results indicated that BDNF expression was suppressed in the hippocampus of OA-treated rats, which resulted in learning and memory deficits. Intra-hippocampal injection of BDNF attenuated this OA-induced cognitive impairment. Finally, our findings indicated an involvement of the PI3K/GSK-3ß/AKT pathway in the mechanism of BDNF in regulating cognitive function. These results indicate that BDNF has beneficial effect on Alzheimer's disease, and highlight the potential of BDNF as a drug target for treatment of Alzheimer's disease.

Role of Nrf2 in bone metabolism.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor expressed in many cell types, including osteoblasts, osteocytes, and osteoclasts. Nrf2 has been considered a master regulator of cytoprotective genes against oxidative and chemical insults. The lack of Nrf2 can induce pathologies in multiple organs. Nrf2 deficiency promotes osteoclast differentiation and osteoclast activity, which leads to an increase in bone resorption. The role of Nrf2 in osteoblast differentiation and osteoblast activity is more complex. Nrf2 mediates anabolic effects within an ideal range. Nrf2 deletion suppresses load induced bone formation and delays fracture healing. Overall, Nrf2 plays an important role in the regulation of bone homeostasis in bone cells.

Activation of cannabinoid receptor 2 enhances osteogenic differentiation of bone marrow derived mesenchymal stem cells.

Bone marrow derived mesenchymal stem cells (BM-MSCs) are considered as the most promising cells source for bone engineering. Cannabinoid (CB) receptors play important roles in bone mass turnover. The aim of this study is to test if activation of CB2 receptor by chemical agonist could enhance the osteogenic differentiation and mineralization in bone BM-MSCs. Alkaline phosphatase (ALP) activity staining and real time PCR were performed to test the osteogenic differentiation. Alizarin red staining was carried out to examine the mineralization. Small interference RNA (siRNA) was used to study the role of CB2 receptor in osteogenic differentiation. Results showed activation of CB2 receptor increased ALP activity, promoted expression of osteogenic genes, and enhanced deposition of calcium in extracellular matrix. Knockdown of CB2 receptor by siRNA inhibited ALP activity and mineralization. Results of immunofluorescent staining showed that phosphorylation of p38 MAP kinase is reduced by knocking down of CB2 receptor. Finally, bone marrow samples demonstrated that expression of CB2 receptor is much lower in osteoporotic patients than in healthy donors. Taken together, data from this study suggested that activation of CB2 receptor plays important role in osteogenic differentiation of BM-MSCs. Lack of CB2 receptor may be related to osteoporosis.

Deletion of Nrf2 reduces skeletal mechanical properties and decreases load-driven bone formation.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor expressed in many cell types, including osteoblasts, osteocytes, and osteoclasts. Nrf2 has been considered a master regulator of cytoprotective genes against oxidative and chemical insults. The lack of Nrf2 can induce pathologies in multiple organs. The aim of this study was to investigate the role of Nrf2 in load-driven bone metabolism using Nrf2 knockout (KO) mice. Compared to age-matched littermate wild-type controls, Nrf2 KO mice have significantly lowered femoral bone mineral density (-7%, p<0.05), bone formation rate (-40%, p<0.05), as well as ultimate force (-11%, p<0.01). The ulna loading experiment showed that Nrf2 KO mice were less responsive than littermate controls, as indicated by reduction in relative mineralizing surface (rMS/BS, -69%, p<0.01) and relative bone formation rate (rBFR/BS, -84%, p<0.01). Furthermore, deletion of Nrf2 suppressed the load-driven gene expression of antioxidant enzymes and Wnt5a in cultured primary osteoblasts. Taken together, the results suggest that the loss-of-function mutation of Nrf2 in bone impairs bone metabolism and diminishes load-driven bone formation.

Functional polymorphisms of the MAO gene with Parkinson disease susceptibility: a meta-analysis.

OBJECTIVE: We carried out a meta-analysis focusing on the relationships between rs1137070 C>T and rs1799836 A>G polymorphisms in the MAO gene as a modifier of Parkinson disease (PD) susceptibility. METHOD: A literature search of the Cochrane Library Database, Web of Science, PubMed, CINAHL, EMBASE, and the Chinese Biomedical Database (CBM) was performed without any language restrictions on articles published before April 10st, 2014. We choose the STATA 12.0 statistical software to deal with statistical data. Crude odds ratios (ORs) estimates with 95% confidence interval (95% CI) were also provided. RESULTS: Fourteen independent case-control studies met our predetermined inclusion criteria and were included in the meta-analysis. Two major polymorphisms rs1137070 C>T and rs1799836 A>G in the MAO gene were performed in this meta-analysis. When all the eligible studies were pooled into the meta-analysis, our results indicated that rs1137070 C>T polymorphism and rs1799836 A>G polymorphism have statistically significant correlation with the increased risk of PD in the majority groups. Ethnicity-stratified analysis revealed a relation between the rs1137070 C>T polymorphism and PD risk among Asians and Caucasians in the majority groups. Additionally, there was an apparent association between the rs1799836 A>G variant and PD risk among the Asian populations under 4 genetic models (G allele vs. A allele: OR=0.84, 95% CI=0.72-0.97, P=0.021; GG vs. AA+AG: OR=1.73, 95% CI=1.25-2.39, P=0.001; GG vs. AA: OR=1.56, 95% CI=1.18-2.04, P=0.002; GG vs. AG: OR=3.42, 95% CI=1.86-6.30, P<0.001; respectively). CONCLUSION: The relationships in the polymorphisms of rs1137070 C>T and rs1799836 A>G in the MAO gene with PD susceptibility observed in our meta-analyses support the view that the MAO gene may play an important role in the development of PD.

A Randomized Trial of Chinese Diaoshi Jifa on Treatment of Dizziness in Meniere's Disease.

Background. Meniere's disease is characterized by refractory dizziness and hearing disturbance. We aimed to investigate the efficacy and tolerance of Diaoshi Jifa, a Chinese hand skill for treating dizziness in Meniere's disease. Methods. An open-labeled, randomized, controlled intervention trial was conducted. Twenty-seven patients diagnosed with Meniere's disease were randomly allocated to control group or experimental group. Both groups were assessed by DHI (dizziness handicap inventory (DHI)) questionnaire score before and within 24 hours of receiving treatment, respectively. Results. Twenty-six participants completed the study, and no adverse event was reported due to Diaoshi Jifa treatment. The difference in the DHI scores between baseline and posttreatment reached significant difference in both groups (63.88 ± 19.94 versus 10.25 ± 9.77 and 54.36 ± 17.97 versus 49.6 ± 20.50). Significant difference in DHI scores was observed between the two groups after treatment (10.25 ± 9.77 versus 49.6 ± 20.50). Further investigation of DHI subscales in the experimental group revealed significant improvement posttreatment in the physical domain, functional domain, and emotional domain. Although higher rate of improvement in the emotional domain compared to physical or functional domains was found, the difference was not statistically significant. Conclusions. Diaoshi Jifa might be a fast, effective, and well-tolerated method for alleviating dizziness in Meniere's disease.

Grand total EEG as a predictive biomarker for cognitive impairment severity in cerebral infarcts of Chinese.

Cerebral infarct (CI) is a common disease of older adults, which increases the risk for cognitive impairment or dementia. CI-associated mild cognitive impairment is a potential prodromal stage of serious cognitive impairment. The grand total EEG (GTE) score is a rating scale for clinical electroencephalography (EEG) analyses, which is useful in the evaluation of different types of cognitive impairment. Sixty-five patients with CI underwent neuropsychological testing and resting state EEG. Spearman rank correlation analysis was used to investigate the relationship between a short version of the GTE score and severity of cognitive impairment in CI. Significant correlations with deteriorating cognition (combined Montreal Cognitive Assessment/clock drawing test) were found for the overall short GTE score (Spearman rank correlation, p = -0.61, r = -0.88491, P = 0.009) and for the subscore "Frequency of Rhythmic Background Activity" (p = -0.63, r = -0.92559, P = 0.007). In conclusion, the GTE short score and Frequency of Rhythmic Background Activity were increased with the deteriorating cognitive impairment in patients with CI.

Differential activation of mTOR complex 1 signaling in human brain with mild to severe Alzheimer's disease.

Mammalian target of rapamycin (mTOR) signaling has been suggested to be effective in modifying cognitive status in animal models of Alzheimer's disease (AD), but little is known about its role in AD patients. We hereby tested whether mTOR signaling was activated and whether activated mTOR signaling was related to the degree of cognitive deficits in patients with AD. Autopsy brain hippocampal tissues were obtained from controls and patients with AD and Western blots were performed using antibodies against mTOR signaling molecules and RagC, an upstream component of mTOR complex 1 (mTORC1) signaling. We found that expression of mTOR/p-mTOR and its downstream targets S6/p-S6 and Raptor/p-Raptor were expressed in the control and AD hippocampus. The expression levels of these signaling molecules were significantly increased in the hippocampus at the severe stages of AD, compared to controls and other stages of AD. Interestingly, Rictor expression level was unaltered. In addition, RagC was increased in the hippocampus at the early, moderate, and severe stages of AD. Our data indicate that mTORC1, but not mTORC2, was activated in the AD brains and that the level of mTOR signaling activation was correlated with cognitive severity of AD patients.

Bickerstaff's brainstem encephalitis, Miller Fisher syndrome and Guillain-Barré syndrome overlap in an asthma patient with negative anti-ganglioside antibodies.

BACKGROUND: Bickerstaff's brainstem encephalitis (BBE), together with Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) were considered to form a continuous clinical spectrum. An anti-GQ1b antibody syndrome has been proposed to underlie the common pathophysiology for the three disorders; however, other studies have found a positive anti-GM1 instead of anti-GQ1b antibody. CASE PRESENTATION: Here we report a 20-year-old male patient with overlapping BBE, MFS and GBS. The patient had a positive family history of bronchial asthma and had suffered from the condition for over 15 years. He developed BBE symptoms nine days after an asthma exacerbation. During the course of illness, he had significantly elevated IgE levels in both serum and cerebrospinal fluid. Serologic analysis of antibodies against ganglioside complexes (anti-GDIa, anti-GDIb, anti-GM1, anti-GM2, anti-GM3, anti-GQIb and anti-GTIb antibodies) showed negative results. CONCLUSIONS: Since asthma has recently been related to autoimmune disease, our case supports an autoimmune mechanism underlying the clinical spectrum composed of BBE, MFS and GBS. However, contrary to a proposed anti-GQ1b antibody syndrome, we would suggest that pathogenesis of this clinical spectrum is not limited to anti-ganglioside antibodies.