Effects of Bone Marrow Mesenchymal Stem Cells on Myelin Repair and Emotional Changes of a Cuprizone-Induced Demyelination Model.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease for which bone marrow mesenchymal stem cells (BM-MSCs) have become one of the most promising tools for treatment. Cuprizone(CPZ) induces demyelination in the central nervous system and its use has established a demyelination sheath animal model which is particularly suitable for studying the effects of BM-MSCs on the remyelination and mood improvement of a demyelinating model mice. METHODS: 70 C57BL/6 male mice were selected and divided into 4 groups: the normal control (n = 20), chronic demyelination (n = 20), myelin repair (n = 15) and cell-treated groups (n = 15). Mice in the normal control group were given a normal diet; the chronic demyelination group mice were given a 0.2% CPZ mixed diet for 14 weeks, mice in the myelin repair and cell-treated groups mice were given a 0.2% CPZ diet for 12 weeks and normal diet for 2 weeks, while the cell-treated group mice were injected with BM-MSCs from the 13th week. The cuprizone-induced demyelination model was successfully established and BM-MSCs extracted, behavioural changes of the mice were detected by open field test, elevated plus maze test and tail suspension test, demyelination and repair of the corpus callosum and astrocyte changes were observed by immunofluorescence and electron microscopy and the concentrations of monoamine neurotransmitters and their metabolites detected by enzyme-linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemistry (HPLC-ECD). RESULTS: Results suggest BM-MSCs were successfully extracted and cultured, and migrated to the demyelinating area of brain tissue after cell transplantation. Compared with the normal control group, the mice in the chronic demyelination group showed obvious anxiety and depression behaviours (p < 0.05); compared with the chronic demyelination group, the anxiety and depression behaviours of the cell-treated group mice were improved (p < 0.05); compared with the normal control group, the demyelination of the corpus callosum region of the chronic demyelination group mice was significant (p < 0.01), while the myelin sheath of the cell-treated and myelin repair groups was repaired when compared with the chronic demyelination group (p < 0.05), and the cell-treated group had a more significant effect than the myelin repair group (p < 0.05). Compared with the normal control group, the number of astrocytes in the corpus callosum of the chronic demyelination group mice was significantly increased (p < 0.01), and the expression of glial fibrillary acidic protein (GFAP) in the cell-treated group was lower than that in the chronic demyelination and myelin repair groups (p < 0.05); the serum concentrations of norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-Hydroxyindole-3-acetic acid (5-HIAA) between the normal control and the chronic demyelination groups were significantly different (p < 0.05). CONCLUSIONS: The CPZ-induced model can be used as an experimental carrier for MS combined with anxiety and depression, and BM-MSC transplantation promotes the repair of myelin sheath and the recovery of emotional disorders in the model.

Atg4b Overexpression Extends Lifespan and Healthspan in Drosophila melanogaster.

Autophagy plays important but complex roles in aging, affecting health and longevity. We found that, in the general population, the levels of ATG4B and ATG4D decreased during aging, yet they are upregulated in centenarians, suggesting that overexpression of ATG4 members could be positive for healthspan and lifespan. We therefore analyzed the effect of overexpressing Atg4b (a homolog of human ATG4D) in Drosophila, and found that, indeed, Atg4b overexpression increased resistance to oxidative stress, desiccation stress and fitness as measured by climbing ability. The overexpression induced since mid-life increased lifespan. Transcriptome analysis of Drosophila subjected to desiccation stress revealed that Atg4b overexpression increased stress response pathways. In addition, overexpression of ATG4B delayed cellular senescence, and improved cell proliferation. These results suggest that ATG4B have contributed to a slowdown in cellular senescence, and in Drosophila, Atg4b overexpression may have led to improved healthspan and lifespan by promoting a stronger stress response. Overall, our study suggests that ATG4D and ATG4B have the potential to become targets for health and lifespan interventions.

Iron overload-induced ferroptosis of osteoblasts inhibits osteogenesis and promotes osteoporosis: An in vitro and in vivo study.

Growing evidence indicates that iron overload is an independent risk factor for osteoporosis. However, the mechanisms are not fully understood. The purpose of our study was to determine whether iron overload could lead to ferroptosis in osteoblasts and to explore whether ferroptosis of osteoblasts is involved in iron overload-induced osteoporosis in vitro and in vivo. Ferric ammonium citrate was used to mimic iron overload conditions, while deferoxamine and ferrostatin-1 were used to inhibit ferroptosis of MC3T3-E1 cells in vitro. The ferroptosis, osteogenic differentiation and mineralization of MC3T3-E1 cells were assessed in vitro. A mouse iron overload model was established using iron dextran. Immunohistochemical analysis was performed to determine ferroptosis of osteoblasts in vivo. Enzyme-linked immunosorbent assays and calcein-alizarin red S labelling were used to assess new bone formation. Dual x-ray absorptiometry, micro-computed tomography and histopathological analysis were conducted to evaluate osteoporosis. The results showed that iron overload reduced cell viability, superoxide dismutase and glutathione levels, increased reactive oxygen species generation, lipid peroxidation, malondialdehyde levels and ferroptosis-related protein expression, and induced ultrastructural changes in mitochondria. Iron overload could also inhibit osteogenic differentiation and mineralization in vitro. Inhibiting ferroptosis reversed the changes described above. Iron overload inhibited osteogenesis, promoted the ferroptosis of osteoblasts and induced osteoporosis in vivo, which could also be improved by deferoxamine and ferrostatin-1. These results demonstrate that ferroptosis of osteoblasts plays a crucial role in iron overload-induced osteoporosis. Maintaining iron homeostasis and targeting ferroptosis of osteoblasts might be potential measures of treating or preventing iron overload-induced osteoporosis.

dNAGLU Extends Life Span and Promotes Fitness and Stress Resistance in Drosophila.

To identify new factors that promote longevity and healthy aging, we studied Drosophila CG13397, an ortholog of the human NAGLU gene, a lysosomal enzyme overexpressed in centenarians. We found that the overexpression of CG13397 (dNAGLU) ubiquitously, or tissue specifically, in the nervous system or fat body could extend fly life span. It also extended the life span of flies overexpressing human Aß42, in a Drosophila Alzheimer's disease (AD) model. To investigate whether dNAGLU could influence health span, we analyzed the effect of its overexpression on AD flies and found that it improved the climbing ability and stress resistance, including desiccation and hunger, suggesting that dNAGLU improved fly health span. We found that the deposition of Aß42 in the mushroom body, which is the fly central nervous system, was reduced, and the lysosomal activity in the intestine was increased in dNAGLU over-expressing flies. When NAGLU was overexpressed in human U251-APP cells, which expresses a mutant form of the Aß-precursor protein (APP), APP-p.M671L, these cells exhibited stronger lysosomal activity and and enhanced expression of lysosomal pathway genes. The concentration of Aß42 in the cell supernatant was reduced, and the growth arrest caused by APP expression was reversed, suggesting that NAGLU could play a wider role beyond its catalytic activity to enhance lysosomal activity. These results also suggest that NAGLU overexpression could be explored to promote healthy aging and to prevent the onset of neurodegenerative diseases, including AD.

Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. METHODS: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. RESULTS: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. CONCLUSIONS: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

Intravesical gemcitabine versus mitomycin for non-muscle invasive bladder cancer: a systematic review and meta-analysis of randomized controlled trial.

BACKGROUND: Mitomycin (MMC) has been frequently used as the compound for intravesical treatment. The relatively new pyrimidine analog gemcitabine (GEM) has exhibited anticancer effect on various solid cancers, such as the advanced bladder cancer. In this study, the GEM and MMC in treating non-muscle invasive bladder cancer (NMIBC) cases was compared through systemic review. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the electronic databases, including Embase, PubMed, Chinese biomedicine literature database, the Cochrane Library, the National Institute for Health and Clinical Excellence, NHS Evidence, Chinese technological periodical full-text database, and Chinese periodical full-text database, were systemically reviewed from inception to October 2018. Then, the RevMan 5.0 software was applied for data analysis. Five randomized controlled trials (RCTs) involving a total of 335 patients were included. RESULTS: For MMC group, the recurrence rate in the mitomycin arm increased compared with that in GEM group (OR = 0.44 95% CI [0.24, 0.78]), and the difference was statistically significant between the two groups. GEM was associated with reduced incidence of chemical cystitis compared with that of MMC (OR = 0.23 95% CI [0.12, 0.44]). Differences in hematuria (OR = 0.46 95% CI [0.16, 1.31]), skin reaction (OR = 0.49 95% CI [0.14, 1.70]) and liver and kidney function damage (OR = 0.51 95% CI [0.09, 2.85]) displayed no statistical significance between the two groups. CONCLUSION: Findings in our study demonstrate the superior efficacy of GEM over MMC in reducing the relapse rate among NMIBC patients following transurethral resection (TUR). In addition, GEM is associated with reduced local toxic effects on the bladder compared with those of MMC. However, more future studies are needed to examine GEM safety when used as the monotherapy or polytherapy for bladder patients. More RCTs with high quality are also required to validate our findings due to the limitations of the current meta-analysis.

Thirty-Day Outcome of a Multicenter Registry Study of Stenting for Symptomatic Intracranial Artery Stenosis in China.

BACKGROUND AND PURPOSE: Although recent trials have suggested that stenting is worse than medical therapy for patients with severe symptomatic intracranial atherosclerotic stenosis, it is not clear whether this conclusion applies to a subset of patients with hypoperfusion symptoms. To justify for a new trial in China, we performed a multicenter prospective registry study to evaluate the safety and efficacy of endovascular stenting within 30 days for patients with severe symptomatic intracranial atherosclerotic stenosis. METHODS: Patients with symptomatic intracranial atherosclerotic stenosis caused by 70% to 99% stenosis combined with poor collaterals were enrolled. The patients were treated either with balloon-mounted stent or with balloon predilation plus self-expanding stent as determined by the operators following a guideline. The primary outcome within 30 days is stroke, transient ischemic attack, and death after stenting. The secondary outcome is successful revascularization. The baseline characteristics and outcomes of the 2 treatment groups were compared. RESULTS: From September 2013 to January 2015, among 354 consecutive patients, 300 patients (aged 58.3±9.78 years) were recruited, including 159 patients treated with balloon-mounted stent and 141 patients with balloon plus self-expanding stent. The 30-day rate of stroke, transient ischemic attack, and death was 4.3%. Successful revascularization was 97.3%. Patients treated with balloon-mounted stent were older, less likely to have middle cerebral artery lesions, more likely to have vertebral artery lesions, more likely to have Mori A lesions, less likely to have Mori C lesions, and likely to have lower degree of residual stenosis than patients treated with balloon plus self-expanding stent. CONCLUSIONS: The short-term safety and efficacy of endovascular stenting for patients with severe symptomatic intracranial atherosclerotic stenosis in China is acceptable. Balloon-mounted stent may have lower degree of residual stenosis than self-expanding stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01968122.

Successful Treatment of Dental Infection-Induced Chronic Cavernous Sinus Thrombophlebitis With Antibiotics and Low-Molecular-Weight Heparin: Two Case Reports.

Two patients developed cavernous sinus thrombophlebitis from a tooth infection. A 36-year-old man experienced a severe headache with bilateral third and sixth cranial nerve palsies after extraction of his left upper third molar. Another 53-year-old diabetic man developed fever, headache, and bilateral complete ophthalmoplegia after a tooth infection. The brain magnetic resonance imaging scans of both patients showed bilateral cavernous sinus partial thrombosis. Broad-spectrum antibiotics plus low-molecular-weight heparin successfully resolved all symptoms. Both patients recovered fully without any recurrence at the 3-month follow-up visit.

The relationship between the frequency of headaches associated with the personal protective equipment and its influencing factors is mediated by depression: A cross-sectional study.

Background: To evaluate the factors affecting personal protective equipment (PPE) associated with headaches in healthcare workers during the first hit of coronavirus disease 2019 (COVID-19) outbreak in China in order to provide evidence for improving the prevention and treatment of PPE-associated headaches in frontline medical personnel. Methods: In this cross-sectional study, the baseline characteristics and the prevalence of the PPE-associated headaches among frontline healthcare workers at Wuhan Taikang Hospital were objectively evaluated by means of a questionnaire survey. We obtained predictors of PPE-associated headaches frequency by multiple regression analyses. The path analysis model was applied to determine the interrelationships between the variables related to PPE-associated headaches frequency. Results: Among the 520 participants, 436 (83.85 %) reported PPE-associated headaches during the anti-epidemic period. Compare with non-PPE-associated headache, age, PHQ-9 score >10, nurses, and PSQI>5were statistically significant found in participants with PPE-associated headaches. Multivariable linear regression showed that the occupation(nurse), pre-existing primary headache diagnosis, headache intensity and depression were risk factors for the frequency of PPE-associated headaches. The path analysis model observed that direct effects from occupation (nurse), pre-existing primary headache diagnosis, headache intensity and depression on the frequency of PPE-associated headaches. Depression indirectly mediated the effects of headache intensity and sleep quality on headache frequency. (All P < 0.05). Conclusion: This study provided a path analysis model that illustrates the relationships between PPE-associated headaches frequency and its related factors among healthcare workers during the COVID-19 pandemic. It is crucial to the management of PPE-associated headaches to reduce its consequences for frontline healthcare workers.

A Long-term outcome of symptomatic middle cerebral artery undergoing intracranial angioplasty or stenting.

PURPOSE: For symptomatic stenosis in the middle cerebral artery (MCA), intracranial angioplasty and stenting are frequently employed. However, limited data exist regarding their long-term impact. Our study demonstrates the long-term advantages in preventing ischemic events through a 5-year follow-up period. METHODS: A set of 41 individuals with symptomatic stenosis in the central cerebral artery (MCA) who underwent angioplasty or stenting procedures between October 2004 and April 2018 at various hospitals in Southwest China were prospectively enrolled in the study. The rates of successful revascularization, complications, imaging observations, and clinical outcomes were systematically assessed. RESULTS: A total of 41 individuals successfully underwent stenting , respectively. After stenting, the extent of stenosis was decreased from 71.8 percent (56 -87.8%) to 24.9 percent (0-45 percent). The mean of follow period is 36.9 ± 13.68 months (range , 11-67 months). There was no deterioration of neurological function or a new ischemic event. A DSA or CTA was conducted after the procedure and demonstrated no in-stent restenosis. No patient experienced restenosis below 50% during the mean follow-up period. The morbidity and mortality rates of the case series were 7.3% and 2.4%, respectively. CONCLUSION: In the treatment of symptomatic MCA atherosclerotic stenoses, intracranial angioplasty & stenting are demonstrated to be technically feasible and safe. Its early & long-term efficacy on ischemic event prevention is acceptable, with a reduced level of restenosis, although the representative sample is tiny.

Protein Restriction Effects on Healthspan and Lifespan in Drosophila melanogaster Are Additive With a Longevity-Promoting Diet.

Aging of the organism is associated diminished response to external stimuli including weakened immune function, resulting in diseases that impair health and lifespan. Several dietary restriction modalities have been reported to improve health and lifespan in different animal models, but it is unknown whether any of the lifespan-extending dietary treatments could be combined to achieve an additive effect. Here, we investigated the effects of halving amino acids components in the HUNTaa diet, a synthetic medium known to extend lifespan in Drosophila. We found that dietary restriction by halving the entire amino acid components (DR group) could further extend lifespan and improve resistance to oxidative stress, desiccation stress, and starvation than flies on HUNTaa diet alone (wt group). Transcriptome analysis of Drosophila at 40, 60, and 80 days of age revealed that genes related to cell proliferation and metabolism decreased with age in the wt group, whereas background stimulus response and amino acid metabolism increased with age. However, these trends differed in the DR group, that is, the DR flies had downregulated stress response genes, including reduced background immune activation. Infection experiments demonstrated that these flies survived longer after feeding infection with Serratia marcescens and Enterococcus faecalis, suggesting that these flies had stronger immune function, and therefore reduced immune senescence. These results demonstrated that halving the entire amino acid components in the HUNTaa diet further extended health and lifespan and suggested that lifespan-extending diet and dietary restriction treatment could be combined to achieve additive beneficial results.

A novel SOD1 mutation in amyotrophic lateral sclerosis with a distinct clinical phenotype.

Familial amyotrophic lateral sclerosis (FALS) accounts for about 5% of cases of the neurodegenerative disorder ALS. At least 100 Cu/Zn superoxide dismutase (SOD1) genetic mutations have been associated with FALS. We identified a FALS family in China with an atypical clinical phenotype. To investigate the SOD1 gene mutations in this family, five exons of the SOD1 gene from each living patient were amplified by PCR and screened by SSCP and direct DNA sequencing. SSCP analysis demonstrated a mutation in exon 2 of SOD1, and DNA sequencing demonstrated the presence of an insertion mutation in exon 2 that has not been reported previously. The mutant SOD1 gene encodes a truncated protein of 35 amino acid residues compared to the normal SOD1 protein of 153 amino acids. In conclusion, The SOD1 exon 2 mutation is likely to be the etiological factor of ALS in this family.

Stent placement for treatment of long segment (≥80 mm) carotid artery stenosis in patients with Takayasu disease.

PURPOSE: To evaluate the effectiveness and safety of carotid artery stent (CAS) placement for treatment of long segment stenosis in patients with Takayasu arteritis. MATERIALS AND METHODS: Between January 2002 and February 2012, all patients with Takayasu arteritis found to have long segment (≥80 mm) carotid artery stenoses at a single institution were retrospectively analyzed. Five patients treated by CAS placement with either long or multiple self-expandable stents were included. All patients had focal neurologic symptoms, including three strokes and two transient ischemic attacks (TIAs). Six self-expanding stents were used in five patients. The mean follow-up period was 19.2 months (range, 6-30 mo); all patients had clinical evaluation, laboratory examination, and vascular imaging follow-up. RESULTS: Improvement in clinical symptoms was shown after successful angioplasty. There were no perioperative or in-hospital deaths. Four patients exhibited persistent relief, and repeated angiography or computed tomography (CT) angiography showed normal flow. One patient stopped taking her medications after CAS placement and became symptomatic 8 months later as a result of a severe in-stent stenosis. CONCLUSIONS: CAS placement was shown to be a feasible option for treating long segment (≥80 mm) stenosis of carotid arteries in patients with Takayasu arteritis with encouraging results.

Incomplete oculomotor nerve palsy in the subarachnoid space caused by traumatic brain injury.

A patient with traumatic brain injury showed incomplete oculomotor nerve palsy in the subarachnoid space. A 12-year-old girl was hospitalized after a head injury. Neuro-ophthalmic examination showed that the left eye had a ptosis and pupillary involvement. An MRI indicated an intracranial hematoma at the basilar portion of the left temple. The ptosis and pupillary involvement improved after elimination of the hematoma. The presentation patterns are best explained by topographic organization of the third nerve fiber within the subarachnoid space. This case suggests that the topographic organization of the third nerve should be considered in diagnosis of oculomotor nerve palsy.

Treatment with carotid angioplasty stent placement for post-stroke depression compared to antidepressants.

OBJECTIVE: To elucidate the differences between carotid angioplasty stent placement (CAS) and antidepressants on post-stroke depression (PSD) in high-grade carotid artery stenosis patients. METHODS: In this prospective, controlled study, 182 cerebral ischemia stroke patients with high-grade carotid artery stenosis who were admitted to the Southwest Hospital of the Third Military Medical University, Chongqing, China, between April 2004 and March 2009 were enrolled. Based on different treatments, the patients were assigned to 2 groups: the CAS group (n=104), and the selective serotonin reuptake inhibitors (SSRIs) group (n=78). All patients were tested using the Hamilton Depression Rating Scale (HDRS) and the National Institutes of Health Stroke Scale (NIHSS) before treatment, one, and 3 months after treatment. RESULTS: The NIHSS score of the CAS group was significantly decreased at one (p=0.007) and 3 months (p=0.006). At one month, the HDRS score of the CAS group was significantly lower than the SSRIs group (p=0.005), and there was no significant difference between these 2 groups at 3 months. CONCLUSION: The CAS relieved PSD and improved neurologic rehabilitation in high-grade carotid artery stenosis patients, and the therapeutic effect was superior to that of SSRIs after one month.

Clinical, Radiological and Pathological Characteristics Between Cerebral Small Vessel Disease and Multiple Sclerosis: A Review.

Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) are a group of diseases associated with small vessel lesions, the former often resulting from the vascular lesion itself, while the latter originating from demyelinating which can damage the cerebral small veins. Clinically, CSVD and MS do not have specific signs and symptoms, and it is often difficult to distinguish between the two from the aspects of the pathology and imaging. Therefore, failure to correctly identify and diagnose the two diseases will delay early intervention, which in turn will affect the long-term functional activity for patients and even increase their burden of life. This review has summarized recent studies regarding their similarities and difference of the clinical manifestations, pathological features and imaging changes in CSVD and MS, which could provide a reliable basis for the diagnosis and differentiation of the two diseases in the future.

Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. Design, Settings, and Participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). Conclusions and Relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02578069.

Enhanced angiogenesis and astrocyte activation by ecdysterone treatment in a focal cerebral ischemia rat model.

BACKGROUND AND PURPOSE: We reported previously that ecdysterone (EDS) improves neurologic function after experimental stroke. However, the underlying mechanism remained unclear. The present study was conducted to test whether ecdysterone improves neurologic function by enhancing astrocyte activation and angiogenesis after focal cerebral ischemia in rats. METHODS: Focal cerebral ischemia model was conducted by middle cerebral artery occlusion (MCAO). EDS was intraperitoneally injected at 20 mg kg1 daily for 7 days after MCAO. Neurologic recovery was assessed using the neurologic severity scores. Microvessel density and GFAP expression were detected with immunostaining and analyzed quantitatively with image system. RESULTS: Treatment with EDS significantly improved functional recovery, along with increases in density of cerebral microvessels and astrocyte activation. Microvessel density was significantly higher in EDS treated group than in ischemia control group at all time points, and reached a peak on day 14. EDS treated group had substantial increment in GFAP immunoreactive cells, darker staining color, more and longer nerve processes, higher GFAP expression and area of immunoreactive cells at each time point. CONCLUSION: Our data suggest that EDS treatment enhanced angiogenesis and astrocyte activation which could contribute to functional recovery.

Five-year follow-up of stenting for a symptomatic posterior cerebral artery stenosis.

Angioplasty and stenting in symptomatic intracranial stenosis is technically possible and may reduce the risk of stroke in patients with symptomatic arterial stenosis. We report a patient with P1 segment stenosis of posterior cerebral artery treated successfully with angioplasty and stenting with a favorable outcome. He had 5 years of clinical and imaging follow-up and no in-stent stenosis or new ischemic event was observed.

[Expression of estrogen receptor alpha in the testis of infertile men with spermatogenic arrest].

OBJECTIVE: To explore the association of spermatogenic arrest with the expression of estrogen receptor alpha (ERalpha) in human testes. METHODS: We examined the testicular biopsy specimens of 120 infertile men by HE staining, detected the expression of ERalpha in the specimens of those with spermatogenic arrest by the two-step immunohistochemical method, and compared the results with those of 10 healthy men. RESULTS: Of the 120 specimens from the infertile men, 31 (25.8%) met the diagnostic criteria of spermatogenic arrest. In the testis tissue of normal men, ERalpha expressed in Sertoli, myoid and Leydig cells, but not in spermatogenic cells, while in the testis tissues of those with spermatogenic arrest, ERalpha expressed lowly in Sertoli, myoid and Leydig cells, with statistically significant differences in immunostaining intensity between the two groups (P < 0.05). CONCLUSION: Androgen receptor (AR) and ERalpha may play a coordinating role in facilitating spermatogenesis. Spermatogenic arrest may be related to a complex series of disorders in cell signal transduction involving AR, ERalpha and HSP90.