Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

Surgical management and outcomes of non-missile open head injury: Report of 44 cases from a single trauma centre.

OBJECTIVE: To retrospectively analyse the surgical management and outcomes of non-missile open head injuries (NMOHI). METHODS: Forty-four patients who suffered from NMOHI were included. The Glasgow outcome score (GOS), computed tomography (CT), aetiology and outcomes and complications at discharge and during a 6-month follow-up were analysed. All patients underwent debridement. Intracranial haematoma evacuation, decompressive craniectomy (DC) or replacement were performed. RESULTS: Motor vehicle accident and struck by/against were the most common causes (43.2% each). At admission, 33 patients had Glasgow coma scores (GCS) > 8 and 27 of them had a GCS score of > 13. Mean follow-up was 8.7 ± 4.3 months. All patients underwent debridement, 20 underwent bone fracture replacement and 27 underwent haematoma evacuation; 11 patients underwent haematoma evacuation and DC and one had bilateral DC. Twenty-seven patients showed good recovery; 11 patients had moderate disability; three patients had severe disability; and three patients died. After 6 months, 32 patients had good recovery and the morbidity of severe disability had decreased to 13.6%. Thirteen patients developed intracranial infection. Post-traumatic epilepsy and hydrocephalus was detected in three patients. Cerebrospinal fluid fistula was found in five patients. Only one patient developed a brain abscess after 6 months. CONCLUSIONS: NMOHI yielded satisfactory recovery and achieved good outcomes.

Extended Suboccipital Retrosigmoid Surgical Approach Is Effective for Resection of Petrous Apex Meningioma.

OBJECTIVE: The aim of this study was to evaluate the clinical features, treatment strategies, and outcomes of patients presented with petrous apex meningiomas. METHODS: In this retrospective clinical study, 17 patients with petrous apex meningiomas were treated microsurgically via an extended suboccipital retrosigmoid approach. Data regarding the general characteristics of the patients, surgical management, and surgery-related outcomes were obtained by reviewing patients' medical records. RESULTS: In the authors' study, the authors report that the use of an extended suboccipital retrosigmoid approach and careful microneurosurgical technique can be used to achieve improved surgical and functional outcomes. This was evidenced by gross tumor resection, which was confirmed in 12 (70.6%) patients, and by partial tumor resection, achieved in the remaining 5 patients. Using this surgical approach, the petrosal vein was preserved in 15 (88.2%) patients. In the remaining 2 (11.8%) patients, this vein was sacrificed. Postsurgical improvement of neurological deficits was consequently observed in 12 (70.6%) patients. Though 3 patients (17.6%) demonstrated a postoperative decline in neurological function, 1 patient significantly recovered facial function at follow-up. One patient with sacrificed petrosal vein experienced loss of functional hearing surgery with no recovery during the follow-up period. No operative mortality was observed. Total resection of petrous apex meningiomas is achievable using an extended suboccipital retrosigmoid approach without permanent surgery-associated neurological deficits in a majority of patients. CONCLUSION: Our primary surgical goal was to achieve maximal tumor resection while maintaining or improving neurological function. Intraoperative protection of the petrosal vein should also be a surgical focus to avoid postoperative complications. Finally, stereotactic radiosurgery can also be useful as a supplemental treatment for postoperative tumor residuals.

Improved neurite outgrowth on central nervous system myelin substrate by siRNA-mediated knockdown of Nogo receptor.

PURPOSE: To investigate the in vitro effect of short interfering RNAs (siRNAs) against Nogo receptor (NgR) on neurite outgrowth under an inhibitory substrate of central nervous system (CNS) myelin. METHODS: Three siRNA sequences against NgR were designed and transfected into cerebellar granule cells (CGCs) to screen for the most effcient sequence of NgR siRNA by using reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. NgR siRNA sequence 1 was found the most efficient which was then transfected into the CGCs grown on CNS myelin substrate to observe its disinhibition for neurite outgrowth. RESULTS: Compared with the scrambled control sequence of siRNA, the NgR siRNA sequence 1 significantly decreased NgR mRNA level at 24 h and 48 h (p <0.05), which was recovered by 96 h after transfection. NgR immunoreactivity was also markedly reduced at 24 and 48 h after the transfection of siRNA sequence 1 compared with that before transfection (p<0.05). The NgR immunoreactivity was recovered after 72 h post-transfection. Moreover, the neurite outgrowth on the myelin substrate was greatly improved within 72 h after the transfection with siRNA sequence 1 compared with the scrambled sequence-transfected group or non-transfected group (p<0.05). CONCLUSION: siRNA-mediated knockdown of NgR expression contributes to neurite outgrowth in vitro.

Effects of Dietary L-carnosine and Alpha-lipoic Acid on Growth Performance, Blood Thyroid Hormones and Lipid Profiles in Finishing Pigs.

The present study was conducted to determine the effects of L-carnosine (LC) and/or alpha-lipoic acid (ALA) supplementation on growth performance, blood thyroid hormones and lipid profiles in finishing pigs. A total of 40 (Landrace×Yorkshire) pigs with an initial body weight of 57.93±3.14 kg were randomly allocated to 4 experimental diets using a 2×2 factorial arrangement with 2 LC supplemental levels (0 or 0.1%) and 2 ALA supplemental levels (0 or 0.03%) in basal diets. The results showed that pigs fed LC-supplemented diets increased final live weight, average daily gain, and average daily feed intake compared to those of pigs fed without LC-supplemented diets (p<0.05). Dietary supplementation with ALA did not affect the growth performance and carcass traits of pigs (p>0.05). Additionally, LC supplementation increased serum triiodothyronine, thyroxine levels, and ALA supplementation increased serum triiodothyronine levels (p<0.05). Serum total cholesterol and triglycerides levels were significantly decreased in LC and ALA supplemented groups, respectively (p<0.05). Moreover, serum low density lipoprotein cholesterol levels were lower in the ALA-supplemented groups than those of pigs fed without ALA-supplemented diets (p<0.05). However, no significant LC×ALA interaction effect on growth performance, blood thyroid hormones and lipid profiles was found. This study suggested that dietary supplementation of LC resulted in better growth performance compared to that of ALA supplementation. L-carnosine and/or ALA supplementation positively modified blood lipid profiles, which may have the potential to prevent cardiovascular diseases.

Prediction Value of Initial Serum Levels of SERPINA3 in Intracranial Pressure and Long-Term Neurological Outcomes in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a severe neurological condition characterized by inflammation in the central nervous system. SERPINA3 has garnered attention as a potential biomarker for assessing this inflammation. Our study aimed to explore the predictive value of postoperative serum SERPINA3 levels in identifying the risk of cerebral edema and its prognostic implications in TBI. This study is a prospective observational study, including 37 patients with TBI who finally met our criteria. The Glasgow Outcome Scale (GOS), Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), and Early Rehabilitation Barthel Index (ERBI) scores at six months after trauma were defined as the main study endpoint. We further calculated the ventricle-to-intracranial-volume ratio (VBR) at 6 months from CT scans. The study included patients with Glasgow Coma Scale (GCS) scores ranging from 3 to 8, who were subsequently categorized into two groups: the critical TBI group (GCS 3-5 points) and the severe TBI group (GCS 6-8 points). Within the critical TBI group, SERPINA3 levels were notably lower. However, among patients with elevated SERPINA3 levels, both the peak intracranial pressure (ICP) and average mannitol consumption were significantly reduced compared with those of patients with lower SERPINA3 levels. In terms of the 6-month outcomes measured via the GOS, LCF, DRS, and ERBI, lower levels of SERPINA3 were indicative of poorer prognosis. Furthermore, we found a negative correlation between serum SERPINA3 levels and the VBR. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) demonstrated the predictive performance of SERPINA3. In conclusion, incorporating the novel biomarker SERPINA3 alongside traditional assessment tools offers neurosurgeons an effective and easily accessible means, which is readily accessible early on, to predict the risk of intracranial pressure elevation and long-term prognosis in TBI patients.

Systematic analysis of levels of evidence supporting Chinese clinical practice guidelines for gastrointestinal disease.

BACKGROUND: Clinical practice guidelines (CPGs) inform healthcare decisions and improve patient care. However, an evaluation of guidelines on gastrointestinal diseases (GIDs) is lacking. This study aimed to systematically analyze the level of evidence (LOE) supporting Chinese CPGs for GIDs. METHODS: CPGs for GIDs were identified by systematically searching major databases. Data on LOEs and classes of recommendations (CORs) were extracted. According to the Grades of Recommendation, Assessment, Development, and Evaluation system, LOEs were categorized as high, moderate, low, or very low, whereas CORs were classified as strong or weak. Statistical analyses were conducted to determine the distribution of LOEs and CORs across different subtopics and assess changes in evidence quality over time. FINDINGS: Only 27.9% of these recommendations were supported by a high LOE, whereas approximately 70% were strong recommendations. There was a significant disparity among different subtopics in the proportion of strong recommendations supported by a high LOE. The number of guidelines has increased in the past 5 years, but there has been a concomitant decline in the proportion of recommendations supported by a high LOE. CONCLUSIONS: There is a general lack of high-quality evidence supporting Chinese CPGs for GIDs, and there are inconsistencies in strong recommendations that have not improved. This study identified areas requiring further research, emphasizing the need to bridge these gaps and promote the conduct of high-quality clinical trials. FUNDING: This study was supported by the National Key R&D Program of China (2022YFC2503604 and 2022YFC2503605) and Special Topics in Military Health Care (22BJZ25).

Cardiometabolic diseases and early cognitive decline: Mitigated by integrated active lifestyle for brain health.

BACKGROUND: Cardiometabolic diseases (CMDs) increases the risk of cognitive decline, but the extent to which this can be offset by adherence to an active integrated lifestyle is unknown. METHODS: This prospective study used the baseline and 2-year follow-up data of 2537 dementia-free elderly ≥60 from PINDEC Project. Lifestyle factors (including physical exercise, social interaction, leisure activities, sleep quality, smoking, and alcohol consumption) were collected and the integrated score was calculated. Participants were divided into three groups based on integrated score tertiles (inactive, ≤3 score; intermediate, 4 score; and active, ≥5). Logistic regression was used in data analysis. RESULTS: 35.2 % participants had 5-6 healthy components, while only 5.4 % had all 6 healthy lifestyles. The multiadjusted odds ratios (ORs, 95 % confidence interval) of early cognitive decline was 1.223 (0.799-1.871) and 1.832 (1.140-2.943) for participants with only one CMD and any two or more CMDs, respectively. An inverse dose-response relationship was found between lifestyle scores and early cognitive decline (Ptrend = 0.017). In participants with active lifestyle, the OR for early cognitive decline comparing the CMDs status of any two or more CMDs vs. CMDs-free was 0.778 (95%CI: 0.302-2.007). Participants with inactive lifestyle and any two or more CMDs had a near 3.4-fold increased risk of early cognitive decline than those without CMDs who had intermediate to active lifestyle (OR = 3.422, 95%CI: 1.764-6.638). LIMITATIONS: Our research lacks information about nutrition. CONCLUSIONS: A dose-response relationship exists between CMDs status and risk of early cognitive decline. However, adherence to an active integrated lifestyle may mitigate this risk.

Dietary supplementation of osthole and icariin improves the production performance of laying hens by promoting follicular development.

Osthole (Ost) and icariin (Ica) are extracted from traditional Chinese medicine Cnidium monnieri and Epimedii Folium, respectively, and both exhibit estrogen-like biological activity. This study aimed to determine the efficacy and safety of combining Ost with Ica on the production performance of laying hens and to explore their possible mechanisms. The production performance, egg quality, residues of Ost and Ica in eggs, serum reproductive hormone levels, expression of ovarian reproductive hormone receptor, proliferation of granulosa cells in small yellow follicles (SYF), and progesterone secretion in large yellow follicles (LYF) related genes and proteins expression were detected. The results showed that adding 2 mg/kg Ost + 2 mg/kg Ica to the feed increased the laying rate, average egg weight, Haugh unit, and protein height of laying hens. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (P4) levels increased, and the expression of ovarian estrogen receptor (ER), follicle-stimulating hormone receptor (FSHR), and progesterone receptor (PGR) mRNA was up-regulated. Additionally, the mRNA and protein levels of steroidogenesis acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450scc), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) increased in LYF. Furthermore, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin E1, and cyclin A2 were up-regulated in SYF. The residues of Ost and Ica in egg samples were not detected by high-performance liquid chromatography (HPLC). In conclusion, dietary supplementation of Ost and Ica increased granulosa cells proliferation in SYF and increased P4 secretion in granulosa cells of LYF, ultimately improving the production performance of laying hens.

Role of METTL3 in Aerobic Glycolysis of Glioma by Regulating m6A/miR-27b-3p/PDK1.

Methyltransferase like 3 (METTL3) has been reported to be dysregulated in glioma. However, its role in aerobic glycolysis of glioma remains unknown. This study was conducted to explore the molecular mechanism by which METTL3 regulates aerobic glycolysis of glioma and provide novel targets for the treatment of glioma. The expression levels of METTL3, microRNA (miR)-27b-3p, and pyruvate dehydrogenase kinase 1 (PDK1) were determined in glioma cell lines and normal human astrocytes. Cell proliferation and aerobic glycolysis were evaluated by cell counting kit-8 and colony formation assays and measurements of glucose uptake, lactate production, adenosine triphosphate, Hexokinase activity, oxygen consumption rate, and extracellular acidification rate. After m6A quantification analysis, methylated RNA immunoprecipitation, and the dual-luciferase assay, the rescue experiments were performed using miR-27b-3p inhibitor or pcDNA3.1-PDK1 with pcDNA3.1-METTL3. METTL3 was lower in glioma cells and METTL3 overexpression reduced aerobic glycolysis. METTL3 increased m6A modification to promote the processing of pri-miR-27b by DGCR8 and the expression of mature miR-27b-3p, and miR-27b-3p targeted and inhibited PDK1 expression. miR-27b-3p inhibition or PDK1 overexpression both neutralized the inhibitory role of METTL3 overexpression in aerobic glycolysis. Overall, METTL3 overexpression increased the expression of mature miR-27b-3p via m6A modification and inhibited PDK1 expression, thus suppressing aerobic glycolysis of glioma.

Netrin-1 upregulates GPX4 and prevents ferroptosis after traumatic brain injury via the UNC5B/Nrf2 signaling pathway.

AIM: We aimed to investigate the regulatory role of Netrin-1 (NTN1) in ferroptosis after traumatic brain injury (TBI) in mice. METHODS: We assessed the expression pattern of NTN1 by RT-PCR, western blot, and immunofluorescence after establishing the TBI model in mice. After treatment with NTN1 shRNA or recombinant NTN1, we determined the biochemical and morphological changes associated with ferroptosis and netrin-1-related pathways. We used Nissl staining to assess lesion volume and Morris water maze and beam-walking test to evaluate ethological manifestation. RESULTS: The mRNA and protein levels of NTN1 were upregulated after TBI. The application of NTN1 shRNA increased the number of FJB positive cells, malondialdehyde (MDA), and reactive oxygen species (ROSs) levels. However, the application of NTN1 recombinant had the opposite effect. Furthermore, knockdown or inhibition of GPX4, Nrf2, and UNC5B counteracted the effects of NTN1 recombinant. Intravenous injection of NTN1 recombinant reduced neuronal loss after CCI and improved motor and cognitive function. CONCLUSION: NTN1 had a neuroprotective effect after TBI and inhibited ferroptosis via activating the UNC5B/Nrf2 pathway. These findings may provide potential therapeutic strategies for TBI.

Hypothermia impairs glymphatic drainage in traumatic brain injury as assessed by dynamic contrast-enhanced MRI with intrathecal contrast.

Introduction: The impact of hypothermia on the impaired drainage function of the glymphatic system in traumatic brain injury (TBI) is not understood. Methods: Male Sprague-Dawley rats undergoing controlled cortical impact injury (CCI) were subjected to hypothermia or normothermia treatment. The rats undergoing sham surgery without CCI were used as the control. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with intrathecal administration of low- and high-molecular-weight contrast agents (Gd-DTPA and hyaluronic acid conjugated Gd-DTPA) was performed after TBI and head temperature management. The semiquantitative kinetic parameters characterizing the contrast infusion and cleanout in the brain, including influx rate, efflux rate, and clearance duration, were calculated from the average time-intensity curves. Results and discussion: The qualitative and semiquantitative results of DCE-MRI obtained from all examined perivascular spaces and most brain tissue regions showed a significantly increased influx rate and efflux rate and decreased clearance duration among all TBI animals, demonstrating a significant impairment of glymphatic drainage function. This glymphatic drainage dysfunction was exacerbated when additional hypothermia was applied. The early glymphatic drainage reduction induced by TBI and aggravated by hypothermia was linearly related to the late increased deposition of p-tau and beta-amyloid revealed by histopathologic and biochemical analysis and cognitive impairment assessed by the Barnes maze and novel object recognition test. The glymphatic system dysfunction induced by hypothermia may be an indirect alternative pathophysiological factor indicating injury to the brain after TBI. Longitudinal studies and targeted glymphatic dysfunction management are recommended to explore the potential effect of hypothermia in TBI.

Effect of the Online Mindfulness-Based Stress Reduction on Anxiety and Depression Status of COVID-19 Patients Treated in Fangcang Hospitals: A Randomized Controlled Trial.

Background: As the focal point of epidemic prevention and control, the mental health of COVID-19 patients cannot be ignored. Online Mindfulness-Based Stress Reduction (MBSR) allows for the provision of conveniently accessible, effective and low-cost interventions on a large scale. We aim to evaluate the effectiveness of an online MBSR intervention in alleviating anxiety and depression among asymptomatic/mild patients limited by COVID-19-related restrictions. Methods: Fifty-eight patients treated in Sanya Fangcang hospital were randomly allocated to either to the experimental group (n = 29) following daily, for 5 days, an online-based mindfulness intervention or to the control group (n = 29). Patients from both groups underwent online questionnaires including assessment of anxiety and depression status at pre- and post-tests using Self-rating Anxiety Scale and Self-Rating Depression Scale. Results: After the online-based MBSR program, the anxiety and depression scores of the patients in the MBSR group decreased significantly in comparison to the scores of those in the control group (respectively η2 = 0.175, η2 = 0.215, p < 0.001). And the proportion of severe anxiety and depression patients in the MBSR group decreased to 0% which lower than the control group, and the proportion of light anxiety and depression patients was significantly more than that in the control group after the MBSR intervention. Conclusion: The online-based MBSR intervention appears to be an effective way of alleviating anxiety and depression symptoms among COVID-19 patients with associated quarantine in Fangcang hospital. Given the seriousness of mental health threat that could be posed by this ongoing pandemic, our study provides a new idea and method for cost-effective and time-efficient interventions in the future of epidemic prevention and control.

Cholesterol paradox in the community-living old adults: is higher better?

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS: In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

The Prognostic Value of Deleted in Colorectal Cancer (DCC) Receptor and Serum Netrin-1 in Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is a common neurological disease. Netrin-1 and deleted in colorectal cancer (DCC) receptor are potential biomarkers associated with nerve regeneration and immune regulation. We aimed to investigate the ability of the DCC receptor and Netrin-1 to predict a high ICP level after operation in severe traumatic brain injury and their prognostic significance. This study is a prospective observational study. We selected 23 patients with traumatic brain injury who had undergone surgical operations as subjects. Immunohistochemical staining was performed on the contusion tissue that was removed by the operation to determine the expression of DCC receptor. At the same time, enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum Netrin-1 content. Determination of intracranial pressure (ICP) value was measured by intraventricular catheter. The Glasgow Outcome Scale (GOS) score at six months after trauma was defined as the main study endpoint. The results showed that serum Netrin-1 concentrations of patients in the critical TBI group (GCS 3-5 points) was significantly lower than that in the severe TBI group (GCS 6-8 points). The ICP peak and average mannitol consumption in the high Netrin-1 group were significantly lower than those in the low Netrin-1 group. DCC receptor-positive patients had a significantly lower ICP peak. There was no significant difference in six month-GOS scores between patients in the high and low Netrin-1 groups, while DCC receptor concentrations below 3.82 ng/mL predicted poor prognosis (GOS 1-3 points). In conclusion, the expression level of the DCC receptor can better evaluate the postoperative high ICP level and prognosis than the level of serum Netrin-1 in severe traumatic brain injury.

Hypothermia reduces glymphatic transportation in traumatic edematous brain assessed by intrathecal dynamic contrast-enhanced MRI.

The glymphatic system has recently been shown to clear brain extracellular solutes and can be extensively impaired after traumatic brain injury (TBI). Despite hypothermia being identified as a protective method for the injured brain via minimizing the formation of edema in the animal study, little is known about how hypothermia affects the glymphatic system following TBI. We use dynamic contrast-enhanced MRI (DCE-MRI) following cisterna magna infusion with a low molecular weight contrast agent to track glymphatic transport in male Sprague-Dawley rats following TBI with hypothermia treatment and use diffusion-weighted imaging (DWI) sequence to identify edema after TBI, and further distinguish between vasogenic and cytotoxic edema. We found that hypothermia could attenuate brain edema, as demonstrated by smaller injured lesions and less vasogenic edema in most brain subregions. However, in contrast to reducing cerebral edema, hypothermia exacerbated the reduction of efficiency of glymphatic transportation after TBI. This deterioration of glymphatic drainage was present brain-wide and showed hemispherical asymmetry and regional heterogeneity across the brain, associated with vasogenic edema. Moreover, our data show that glymphatic transport reduction and vasogenic edema are closely related to reducing perivascular aquaporin-4 (AQP4) expression. The suppression of glymphatic transportation might eliminate the benefits of brain edema reduction induced by hypothermia and provide an alternative pathophysiological factor indicating injury to the brain after TBI. Thus, this study poses a novel emphasis on the potential role of hypothermia in managing severe TBI.

Tailored Lipoprotein-Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor-Stimulated Macropinocytosis.

Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein-like nanostructure is developed to amplify their internalization into GICs through receptor-stimulated macropinocytosis. As CXCR4 is highly expressed on GICs and glioma tumor sites, meanwhile, the activation of CXCR4 induces the receptor-stimulated macropinocytosis pathway in GICs, this CXCR4 receptor-stimulated lipoprotein-like nanoparticle (SLNP) achieves efficient accumulation in GICs in vitro and in vivo. By carrying microRNA-34a in the core, this tailored SLNP reduces sex-determining region Y-box 2 and Notch1 expression, powerfully inhibits GICs stemness and chemoresistance, and significantly prolongs the survival of GICs-bearing mice. Taken together, a tailored lipoprotein-based nanostructure realizes efficient GICs accumulation and therapeutic effect through receptor-stimulated macropinocytosis, providing a powerful nanoplatform for RNA interference drugs to combat glioma.

TROY interacts with RKIP to promote glioma development.

TROY is a component of the Nogo receptor complex and plays the key role in neuronal survival, migration, and differentiation. Here, we show the up-regulation of TROY in human glioma tissues and cells. Inhibition of TROY expression slowed glioma development in vivo and in vitro. Raf kinase inhibitor (RKIP) was found to interact with TROY. The physical interaction of TROY/RKIP was confirmed via co-immunoprecipitation (co-IP) assays. Furthermore, we found that the TROY/RKIP interaction was enhanced by fetal bovine serum (FBS) exposure, and TROY knockdown also led to down-regulation of NF-κB. Finally, disruption of the TROY/RKIP interaction using the TAT-TROY (234-371 aa) protein reduced the glioma development in xenografted mice. This suggests the TROY/RKIP interaction is a potential target for therapy of gliomas.

Traumatic subdural effusion evolves into chronic subdural hematoma: two stages of the same inflammatory reaction?

Traumatic subdural effusion (TSE) is one of the main associated complications of brain trauma. About half of the asymptomatic TSEs ultimately evolve into chronic subdural hematomas (CSDHs), most of which will be inevitably treated by surgical evacuation. With the emergence of subdural hydroma (SDH), rupture of bridge-veins, bleeding of the hydroma wall, hyperfunction of fibrinolysis and increasing protein content in the hydroma are some of the traditionally cited explanations of the pathogenesis of TSE evolving into CSHD. Despite intensive research and subsequent advances in surgical techniques of CSDH, a single treatment with measurable clinical impact on the evolution interruption has yet to be investigated. Compared with peripheral venous blood, inflammatory cytokines were elevated in TSE and CSDH demonstrated by a number of investigators. Neoformation of capillaries, vascular hyper-permeability, serum protein exudation and other characteristics of aseptic inflammatory reaction were observed. Meanwhile, steroid was applied to treat CSDH in several groups, which was generally used as an effective anti-inflammatory agent. Based on systemic thinking, we hypothesize that TSE and CSDH are different stages, with different appearances, of the same inflammatory reaction. The evolution from TSE into CSDH and propagation of CSDH seem to be the results of local aseptic inflammation. Our hypothesis holds potential as a target for therapeutic intervention.

Meningioma in the elderly: Characteristics, prognostic factors, and surgical strategy.

Meningioma is one of the most common intracranial tumors. It has the features of benign and slow growing. We focused on the meningioma in the elderly, retrospectively analyzed 528 valid meningioma patients, including 115 (21.8%) patients older than 65 years old. The elderly patients were shown to have significantly larger tumor diameter (mean [±SD] 43.4 ±â€¯18.0 mm) comparing with the young group (mean [±SD] 37.6 ±â€¯16.5 mm, p < 0.01). Post-operative KPS was significantly lower in the elderly group (mean [±SD] 79.64 ±â€¯26.37) than the young group (mean [±SD] 88.81 ±â€¯17.36, p < 0.01). Multivariate regression of post-operative KPS scales at discharge and 6 months follow-up showed operative complications, pre-operative comorbidities, tumor diameter, and challenging location had a significant impact on the outcome. However, tumor blood supply, Simpson grades, pathology, and pre-operative symptoms were shown to have less impact on the post-operative KPS scale. The outcome for meningioma in elderly patients was affected by factors related more to the safety of the operation than characteristics of the tumor. Therefore, rather than achieving total resection, conservative and safety preferential treatment strategies should be regarded as a higher priority for better quality of life.