APOE2 protects against Aß pathology by improving neuronal mitochondrial function through ERRα signaling.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease and apolipoprotein E (APOE) genotypes (APOE2, APOE3, and APOE4) show different AD susceptibility. Previous studies indicated that individuals carrying the APOE2 allele reduce the risk of developing AD, which may be attributed to the potential neuroprotective role of APOE2. However, the mechanisms underlying the protective effects of APOE2 is still unclear. METHODS: We analyzed single-nucleus RNA sequencing and bulk RNA sequencing data of APOE2 and APOE3 carriers from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort. We validated the findings in SH-SY5Y cells and AD model mice by evaluating mitochondrial functions and cognitive behaviors respectively. RESULTS: The pathway analysis of six major cell types revealed a strong association between APOE2 and cellular stress and energy metabolism, particularly in excitatory and inhibitory neurons, which was found to be more pronounced in the presence of beta-amyloid (Aß). Moreover, APOE2 overexpression alleviates Aß1-42-induced mitochondrial dysfunction and reduces the generation of reactive oxygen species in SH-SY5Y cells. These protective effects may be due to ApoE2 interacting with estrogen-related receptor alpha (ERRα). ERRα overexpression by plasmids or activation by agonist was also found to show similar mitochondrial protective effects in Aß1-42-stimulated SH-SY5Y cells. Additionally, ERRα agonist treatment improve the cognitive performance of Aß injected mice in both Y maze and novel object recognition tests. ERRα agonist treatment increased PSD95 expression in the cortex of agonist-treated-AD mice. CONCLUSIONS: APOE2 appears to enhance neural mitochondrial function via the activation of ERRα signaling, which may be the protective effect of APOE2 to treat AD.

Ezetimibe attenuates functional impairment via inhibition of oxidative stress and inflammation in traumatic spinal cord injury.

Sustained inflammation after a traumatic spinal cord injury (TSCI) triggers oxidative stress and neuronal apoptosis, hindering functional recovery. Ezetimibe (EZE) has been reported to have anti-inflammatory and antioxidative properties in hepatology-related diseases, but its potential role in SCI remains unclear. In this study, we evaluated the therapeutic effect of EZE on inflammatory microglia and in an SCI model and elucidated the underlying mechanism. First, we stimulated the BV2 microglia cell line with LPS, and we also induced moderate spinal cord injuries in adult male C57BL/6 mice. Both the cells and mice were treated with EZE, and we investigated inflammation, oxidative stress, neurologic damage, and motor function in vitro and in vivo, respectively. Our findings demonstrated that EZE administration attenuates inflammation in microglia by regulating the AMPK/Nrf2 axis. Furthermore, EZE treatment reduced inflammation and oxidative stress levels in the injured spinal cord. Additionally, treatment with EZE decreased glial scarring and improved motor function recovery, indicating the protective role of EZE in SCI. EZE was found to have anti-inflammatory and antioxidative effects on SCI, and it modulated the AMPK/Nrf2 pathway in microglia. Moreover, EZE prevented histological destruction of the spinal cord tissue. In conclusion, EZE shows promise as a drug to protect neurologic integrity following post-SCI.

GbCYP72A1 Improves Resistance to Verticillium Wilt via Multiple Signaling Pathways.

Verticillium dahliae is a fungal pathogen that causes Verticillium wilt (VW), which seriously reduces the yield of cotton owing to biological stress. The mechanism underlying the resistance of cotton to VW is highly complex, and the resistance breeding of cotton is consequently limited by the lack of in-depth research. Using quantitative trait loci (QTL) mapping, we previously identified a novel cytochrome P450 (CYP) gene on chromosome D4 of Gossypium barbadense that is associated with resistance to the nondefoliated strain of V. dahliae. In this study, the CYP gene on chromosome D4 was cloned together with its homologous gene on chromosome A4 and were denoted as GbCYP72A1d and GbCYP72A1a, respectively, according to their genomic location and protein subfamily classification. The two GbCYP72A1 genes were induced by V. dahliae and phytohormone treatment, and the findings revealed that the VW resistance of the lines with silenced GbCYP72A1 genes decreased significantly. Transcriptome sequencing and pathway enrichment analyses revealed that the GbCYP72A1 genes primarily affected disease resistance via the plant hormone signal transduction, plant-pathogen interaction, and mitogen-activated protein kinase (MAPK) signaling pathways. Interestingly, the findings revealed that although GbCYP72A1d and GbCYP72A1a had high sequence similarity and both genes enhanced the disease resistance of transgenic Arabidopsis, there was a difference between their disease resistance abilities. Protein structure analysis revealed that this difference was potentially attributed to the presence of a synaptic structure in the GbCYP72A1d protein. Altogether, the findings suggested that the GbCYP72A1 genes play an important role in plant response and resistance to VW.

LINC00152 acts as a potential marker in gliomas and promotes tumor proliferation and invasion through the LINC00152/miR-107/RAB10 axis.

PURPOSE: Aberrant expression of long noncoding RNAs plays a pivotal role in tumorigenesis. Recently, several studies have showed that the LINC00152 gene is upregulated in a variety of tumors and plays an oncogene role; however, its underlying molecular mechanisms in glioblastoma remain unclear. In this study, we prepare to investigate the biological role and underlying molecular mechanisms of LINC00152 in glioblastoma cells. METHODS: Bioinformatics analysis to identify LINC00152 expression, Cell Counting kit-8 assay and Colony formation assay were used to evaluate proliferation, Flow cytometric analysis was used to evaluate apoptosis, Cell Matrigel invasion assay and Wound healing assay was used to evaluate invasion, Western blot analysis to check protein expression level, Mouse xenograft models was used to check cell proliferation in vivo. RESULTS: In this study, we found that LINC00152 was upregulated in gliomas and its expression was significantly associated with high tumor aggressiveness and poor outcomes for glioma patients. Functionally, the knockdown of LINC00152 not only inhibited malignant behaviors of glioma, such as proliferation and invasion of glioma cells and induced apoptosis in vitro but also suppressed tumorigenesis in vivo. Mechanistically, results of the bioinformatics analysis and experimental studies confirmed that LINC00152 and RAB10 as the targets of miR-107, and LINC00152 might act as a sponge for miR-107 to regulate the expression of RAB10 in glioblastoma. Additionally, silencing miR-107 reversed the effects induced by LINC00152 knockdown on glioblastoma cells both in vitro and in vivo. CONCLUSION: Our data suggested that LINC00152 is a candidate prognostic marker of glioma, and that the LINC00152/MIR-107/RAB10 axis plays a pivotal role in regulation of the glioma malignancy, and therefore, targeting the axis might be an effective therapeutic strategy to treat glioma.

RUNX3 Polymorphisms Affect the Risk of Ankylosing Spondylitis.

BACKGROUND We aimed to assess the potential association of runt-related transcription factor 3 (RUNX3) gene variants with ankylosing spondylitis (AS) susceptibility among Chinese Han people. MATERIAL AND METHODS Genotyping for RUNX3 variants was accomplished through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 115 AS patients and 102 healthy controls. Genotypes distributions of the polymorphisms in controls was assessed for their deviation from Hardy-Weinberg equilibrium (HWE). Moreover, odds ratio (OR) with 95% confidence interval (95%CI) was achieved using chi-square analysis to evaluate AS risk related to RUNX3 polymorphisms. Additionally, logistic regression analysis produced adjusted OR values. RESULTS Genotypes distribution of rs760805 and rs11249206 polymorphisms conformed to HWE in the control group (P>0.05). TT genotype of rs760805 appeared more frequently among AS cases than in controls (P=0.033), indicating its significant association with increased risk of AS onset (OR=2.309, 95%CI=1.069-4.892). The carriage of T allele in rs760805 also heightened AS incidence, in comparison to A allele (OR=1.578, 95%CI=1.075-2.316, P=0.020). Moreover, the carriage of AT+TT genotype in rs760805 and TT genotype in rs11249206 obviously increased risk of AS onset (OR=2.585, 95%CI=1.062-6.288). CONCLUSIONS RUNX3 rs760805 polymorphism can contribute to AS incidence in Chinese Han people. The interaction of the 2 polymorphisms may be a risk factor for AS.

The rs6427384 and rs6692977 Single Nucleotide Polymorphisms of the Fc Receptor-Like 5 (FCRL5) Gene and the Risk of Ankylosing Spondylitis: A Case Control Study in a Single Center in China.

BACKGROUND The study aimed to explore the genetic association of Fc receptor-like 5 (FCRL5) gene variants (rs6427384 and rs6692977) with ankylosing spondylitis risk in Chinese Han population. MATERIAL AND METHODS Genotyping for FCRL5 gene variations rs6427384 and rs6692977 was implemented among 130 ankylosing spondylitis cases and 135 healthy persons, through polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Frequency dissimilarity for 2 polymorphisms was compared between 2 groups using chi-square test. The association strength of FCRL5 gene polymorphism with ankylosing spondylitis risk was estimated by odds ratios with 95% confidence intervals. RESULTS The frequencies of rs6427384 CC genotype and C allele were significantly lower in the case group than that in the control group (P<0.05), which suggested that C allele of rs6427384 polymorphism might offer protection against ankylosing spondylitis onset. Whereas only 2 genotypes of rs6692977 were detected in the control group, and no significant association was found with ankylosing spondylitis susceptibility. CONCLUSIONS FCRL5 gene polymorphism rs6427384 was correlated to ankylosing spondylitis occurrence among Chinese Han population, while rs6692977 was not.

Dissection of complicate genetic architecture and breeding perspective of cottonseed traits by genome-wide association study.

BACKGROUND: Cottonseed is one of the most important raw materials for plant protein, oil and alternative biofuel for diesel engines. Understanding the complex genetic basis of cottonseed traits is requisite for achieving efficient genetic improvement of the traits. However, it is not yet clear about their genetic architecture in genomic level. GWAS has been an effective way to explore genetic basis of quantitative traits in human and many crops. This study aims to dissect genetic mechanism seven cottonseed traits by a GWAS for genetic improvement. RESULTS: A genome-wide association study (GWAS) based on a full gene model with gene effects as fixed and gene-environment interaction as random, was conducted for protein, oil and 5 fatty acids using 316 accessions and ~ 390 K SNPs. Totally, 124 significant quantitative trait SNPs (QTSs), consisting of 16, 21, 87 for protein, oil and fatty acids (palmitic, linoleic, oleic, myristic, stearic), respectively, were identified and the broad-sense heritability was estimated from 71.62 to 93.43%; no QTS-environment interaction was detected for the protein, the palmitic and the oleic contents; the protein content was predominantly controlled by epistatic effects accounting for 65.18% of the total variation, but the oil content and the fatty acids except the palmitic were mainly determined by gene main effects and no epistasis was detected for the myristic and the stearic. Prediction of superior pure line and hybrid revealed the potential of the QTSs in the improvement of cottonseed traits, and the hybrid could achieve higher or lower genetic values compared with pure lines. CONCLUSIONS: This study revealed complex genetic architecture of seven cottonseed traits at whole genome-wide by mixed linear model approach; the identified genetic variants and estimated genetic component effects of gene, gene-gene and gene-environment interaction provide cotton geneticist or breeders new knowledge on the genetic mechanism of the traits and the potential molecular breeding design strategy.

Neurotropin inhibits neuroinflammation via suppressing NF-κB and MAPKs signaling pathways in lipopolysaccharide-stimulated BV2 cells.

Neurotropin (NTP) is a widely used drug in China and Japan mainly for the treatment of chronic pain and peripheral inflammation. Nevertheless, the effects of NTP on neuroinflammation have not been explored. In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively. Western blotting was conducted to measure the protein levels of major genes in MAPKs and NF-κB signaling pathways. Results demonstrated that NTP could attenuate the production of pro-inflammatory cytokines. Furthermore, NTP inhibited the activation of NF-κB signaling by decreasing the translocation of NF-κB p65 to the nucleus and suppressed the MAPKs signaling pathway via inhibition of the phosphorylation of p38, ERK and JNK. Taken together, these findings suggest that neurotropin exerts anti-inflammatory effects by suppressing the production of pro-inflammatory mediators via inhibition of NF-κB and MAPKs signaling pathways in LPS-stimulated BV-2 cells.

Tooth loss as a risk factor for dementia: systematic review and meta-analysis of 21 observational studies.

BACKGROUND: Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk. METHODS: An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model. RESULTS: The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90-3.61, P < 0.001, I2 = 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41-1.70, P = 0.13, I2 = 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16. CONCLUSIONS: Findings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.

Late-onset cystic brain necrosis after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Cystic brain radionecrosis (CBRN) is a late-onset devastating complication after radiotherapy for head and neck neoplasms, especially for nasopharyngeal carcinoma (NPC). To our knowledge, it has scarcely been reported. METHODS: We retrospectively reviewed all available medical records of NPC patients with CBRN who were treated with surgical intervention. RESULTS: Sixteen patients were identified in this study and the mean latency of CBRN was 9.2 ± 0.9 years. The total irradiation dose of the nasopharynx ranged from 60 to 78 Gy. Cyst-like lesions were observed and there were slightly enhancements on the cyst wall in five patients on patients' brain MRI. All the included patients underwent surgical resection of the cystic necrotic lesion thought temporal approach. Specimens from surgery revealed reactive gliosis and immunopositive cytokines including TNF-α, IL-6 and HIF-2α. Only one patient experienced recurrence and received reoperation after surgery. All the other patients made a good recovery and no operation-related mortality was observed. CONCLUSIONS: CBRN is a delayed but irreversible neurological sequel in irradiated NPC patients. Post-radiotherapy follow-up is quite necessary for those with high risk of CBRN. Proper treatment is needed for early CBRN patients to suppress inflammation in the brain. Timely neurosurgery may benefit patients with late-stage CBRN by alleviating increased intracranial pressure and inflammatory responses.

Hearing impairment and risk of Alzheimer's disease: a meta-analysis of prospective cohort studies.

Observational studies suggested an association between hearing impairment and cognitive disorders. However, whether hearing impairment is an independent risk factor or a harbinger of Alzheimer's disease remains controversial. Our goal was to assess the association between hearing impairment (HI) and the risk of Alzheimer's disease (AD) by conducting a meta-analysis of prospective cohort studies. We comprehensively searched the PubMed, Embase, Web of Science and Cochrane Library databases on January 19, 2016 to incorporate all the prospective cohort studies meeting the inclusion criteria to perform a systematic review and meta-analysis. Four prospective cohort studies with comparison between hearing impairment and normal hearing were incorporated, with 7461 participants. The outcomes of three studies were the incidence of Alzheimer's disease and the outcome of the fourth study was the incidence of mild cognitive impairment. The overall combined relative risk of people with hearing impairment to develop Alzheimer's disease was 4.87 (95% CI 0.90-26.35; p = 0.066), compared with the control group. Since both Alzheimer's disease and mild cognitive impairment are cognitive disorders, we incorporated all the four studies and the overall combined relative risk was 2.82 (95% CI 1.47-5.42; p = 0.002), indicating that the difference was significant. This meta-analysis suggests that hearing impairment significantly increases the risk of cognitive disorders and future well-designed prospective cohort studies are awaited to confirm the association between hearing impairment and risk of Alzheimer's disease.

Bilateral ptosis as first presentation of cytophagic histiocytic panniculitis: a case report.

BACKGROUND: Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis that may progress to panniculitis-like T-cell lymphoma. We report a case of CHP that first manifested as bilateral ptosis, which is the first reported case of this presentation. CASE PRESENTATION: A 25-year-old woman without medical history was referred to the neurology department of our hospital for evaluation of bilateral ptosis. Three months previously, she suddenly complained of bilateral ptosis without apparent cause. Simultaneously, non-painful tender subcutaneous nodules and eschar-like skin lesions were observed on her extremities and trunk. A diagnosis of CHP was made based on skin biopsy from the left thigh showing lobular panniculitis, vasculitis, and adiponecrosis, with infiltration of inflammatory cells, including lymphocytes, histiocytes, and phagocytic histiocytes. Her condition continued to worsen with corticosteroid and immunosuppressive agent (thalidomide) treatment. Significant improvement was noticed after three cycles of chemotherapy of THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone). CONCLUSIONS: CHP is a rare condition whose clinical presentation may include bilateral ptosis and biopsy is required for diagnosis of CHP.

Effects of root exudates of bivalent transgenic cotton (Bt+CpTI) plants on antioxidant proteins and growth of conventional cotton (Xinluhan 33).

A greenhouse experiment was conducted to assess the adverse impact of transgenic cotton on ecosystem and environment via effect of transgenic Bt+CpTI cotton root exudates on growth and antioxidant activity of conventional parental cotton. Results showed elevated reductive and oxidative species activities in the leaves of conventional parental cotton seedlings treated with varying concentrations of transgenic cotton root exudates. Compared to control, 14.9% to 39.9% increase in catalase, 8.8% to 114% increase in for peroxidase, 21.3% to 59.7% increase in phenylalanine ammonia-lyase and 5.8 to 19.5 fold in ascorbate specific peroxidase was observed. However, biomass and height of conventional cotton seedlings were not affected by any concentration of transgenic cotton root exudates. These results suggested that cultivation of transgenic Bt+CpTI cotton plants poses little risk to conventional parental cotton based on their root interactions.

Ionic liquid-assisted fabrication of copper hydroxyphosphate nanocrystals with exposed {100} facets for enhanced photocatalytic activity.

Libethenite Cu2PO4OH nanocrystals with different morphologies were prepared by an ionic liquid-assisted hydrothermal route, and were further investigated as photocatalysts under visible-light irradiation. The Cu2PO4OH elongated truncated bipyramids exposing {100} facets exhibit superior photocatalytic activity compared to other particles, which can be attributed to the presence of 100% Cu5c atoms on {100} facets. It is highly expect this research can provide a useful fundamental understanding of shape-dependent photocatalytic performance of copper hydroxyphosphate.

Sertraline plus deanxit to treat patients with depression and anxiety in chronic somatic diseases: a randomized controlled trial.

BACKGROUND: Patients in chronic somatic diseases are often accompanied with depression and anxiety, remission of which may be observed in the third or fourth week after applying common antidepressant medications. We investigate the efficacy and safety of sertraline plus deanxit on patients with depression and anxiety in chronic somatic diseases. METHODS: 75 Patients who met the criteria were randomly assigned to deanxit group or placebo group: sertraline (75 mg/day) plus deanxit (one piece/day) (N = 38), or sertraline (75 mg/day) plus placebo (one piece/day) (N = 37) for 2 weeks, both groups received sertraline (75 mg/day) in the following 2 weeks. Changes from baseline to day 4, day 8, day 15, and day 29 in Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) total scores were the efficacy measures. Adverse events were monitored and registered systematically during the trial. RESULTS: Response rates for HAM-D scores in deanxit group and placebo group were significantly different on day 8(55.26% ± 2.56% VS 24.32% ± 2.19%, p = 0.006) and day 15(78.95% ± 3.89% VS 40.54% ± 4.18%, p = 0.001), while no statistical differences were observed on day 4 and day 29. Respectively, response rates for HAM-A scores on day 4 (34.21% ± 2.21% VS 8.11% ± 1.37%, p = 0.006), day 8 (57.89% ± 3.56% VS 18.92% ± 2.68%, p = 0.001) and day 15 (78.95% ± 4.37% VS 43.24% ± 4.68%, p = 0.002), favoring the deanxit group. However, HAM-A scores were not remarkably different at the end point. The overall safety profile of both groups was favorable with no distinct differences. CONCLUSIONS: The efficacy was exhibited in the deanxit group, with evidence for similar safety. The rapid onset of sertraline plus short-term deanxit indicated that it might be an inspiring strategy to manage depression and anxiety within the first two weeks in chronic somatic diseases.

Stepwise Therapy for Treating Tuberculosis of the Upper Cervical Spine: A Retrospective Study of 11 Patients.

AIMS: Tuberculosis of the upper cervical spine is a rare occurrence with serious consequence, and its optimal treatment protocol remains inconclusive. This study aims at investigating the clinical characteristics and management outcomes of the stepwise therapy for different stages of tuberculosis of the upper cervical spine. METHODS: We conducted a retrospective analysis of 11 patients with tuberculosis of the upper cervical spine who received anti-tuberculosis chemotherapy for 15 months. Two infants were treated by individualized chemotherapy, while 9 patients with retropharyngeal abscess were first treated with CT-guided percutaneous puncture, and the catheter was used to administer local chemotherapy. Two of these 9 patients continued to receive posterior instrumentation due to atlantoaxial subluxation. Patients were followed up clinically and radiologically for an average period of 60 months. RESULTS: Two patients underwent catheter change due to catheter falling off and blockage, 2 patients had gastrointestinal side effects, and 2 patients had drug-induced hepatitis derived from the chemotherapy. Mean erythrocyte sedimentation rate was 10.27 mm/h (range 4-16 mm/h) and average visual analogue scale score was 2.55. A total of 11 cases underwent routine anti-tuberculosis chemotherapy for 15 months. 9 of 11 cases received supplementary surgical therapy, and all patients were cured at the final follow-up. CONCLUSION: Standard anti-tuberculosis chemotherapy is the cornerstone of stepwise therapy for tuberculosis of the upper cervical spine. Local chemotherapy is effective and minimally invasive for patients with severe local symptoms without spinal cord compression. Just as in patients with atlantoaxial instability, open fixation and bone grafting are necessary.

Radiation-induced brachial plexus injury after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: Radiation-induced brachial plexus injury is a devastating complication that occurs after radiotherapy in the vicinity of the brachial plexus. Nasopharyngeal carcinoma, the most common type of cancer in Guangdong Province, is primarily treated with radiotherapy with subsequent side effects. However, radiation-induced brachial plexus injury is rarely reported in nasopharyngeal carcinoma. To draw attention to this correlation, we analyzed the clinical characteristics including the imaging findings of 10 patients suffering from radiation-induced brachial plexus injury for nasopharyngeal carcinoma. METHODS: We considered the patients' medical histories, analyzed their clinical characteristics, and monitored the long-term efficacy of treatment. RESULTS: The total irradiation dose of the nasopharynx ranged from 66.6 to 74 Gy, and that of the supraclavicular fossa ranged from 60 to 70 Gy. The mean latency was 8.2 ± 5.5 years. Seven patients initially complained of bilateral weakness, and three patients complained of isolated pain. The injuries of eight patients reached Grade 3 or worse. Magnetic resonance imaging showed a low signal on T1-weighted images and a high signal on short tau inversion recovery sequences in all cases. Swollen nerve fibers were clearly displayed in magnetic resonance diffusion tensor imaging. Electromyography showed myokymia in three patients. With conservative therapy, only one patient was temporarily relieved of pain, while the conditions of others were not ameliorated. CONCLUSIONS: Radiation-induced brachial plexus injury is a late but catastrophic complication in patients with nasopharyngeal carcinoma. Clinicians should be aware of radiation-induced brachial plexus injury when deciding on treatment and should give them regular follow-up post radiotherapy.

A case study using total en bloc sacrectomy and neuroanastomosis for sacral tumor.

PURPOSE: To study the oncological and functional outcomes of patients undergoing en bloc tumor excisions and neuroanastomosis for sacral tumors. METHODS: Five patients who underwent en bloc total sacrectomy and neuroanastomosis from January 2006 to August 2010 were observed. A procedure combining the anterior and posterior approach was used on these patients. Neuroanastomosis was performed after sacrectomy. Perioperative complications and postoperative functions in these patients were analyzed. RESULTS: All patients had partial or complete loss of bladder and bowel functions, foot plantar flexion weakness and increased residual urine volume after surgery. Three patients were ambulatory. After 6 months, four patients were disease-free, two patients reported slightly improved bladder and bowel functions, four patients could ambulate with a walking stick and the one patient with sarcoma had other metastases and died after 8 months. After 1 year, two patients reported improved bladder and bowel functions, one patient slightly improved bladder and bowel functions and there was no change in one patient. CONCLUSION: Successful neuroanastomosis of sacral nerve roots does not occur in all patients, but lower limb, bladder and bowel functions can improve with time after the surgery.

Progression of cognitive dysfunction in NPC survivors with radiation-induced brain necrosis: A prospective cohort.

BACKGROUND AND PURPOSE: The evidence of longitudinal changes in cognition in nasopharyngeal carcinoma (NPC) survivors with radiation-induced brain necrosis (RIBN) after radiotherapy (RT) remained insufficient. We aimed to estimate the clinical progression rate of cognitive decline and identify patients with differential decline rates. MATERIALS AND METHODS: Based on an ongoing prospective cohort study, NPC patients aged ≥18 years old and diagnosed with RIBN were included in this current analysis if they finished the time frame of 3-year follow-up and had at least twice cognition assessments. The Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess the cognitive state. Linear mixed-effect models were used to analyze the annual progression rates of MoCA total and seven sub-items scores. RESULTS: Among 134 patients in this study, the transition probability from normal to mild/moderate cognitive dysfunction were 14.2 % (19/134) and 1.49 % (2/134) respectively during the median follow-up time of 2.35 years. The total MoCA score declined by -0.569 (SE 0.208) points annually (p = 0.008). Patients with ≤6 years of duration from RT to RIBN have higher annual progression rate of total scores [-0.851 (SE 0.321), p = 0.013; p for interaction = 0.041]. CONCLUSION: Our findings of the annual decline rate of cognition in NPC patients with RIBN from a 3-year longitudinal data, particularly for those who developed RIBN rapidly after RT, have important implications for the upcoming clinical trials designed to prevent or decrease cognitive decline in NPC patients with RIBN, regarding the selection of study patients and the calculation of sample size.

Amyloid ß oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction.

BACKGROUND: Although abnormal accumulation of amyloid beta (Aß) protein is thought to be the main cause of Alzheimer's disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid ß induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aß deposition and vascular injuries. Recent studies have revealed that pericytes play a substantial role in the vasculopathy of AD. Additional research is imperative to attain a more comprehensive understanding. METHODS: Two-photon microscopy and laser speckle imaging were used to examine cerebrovascular dysfunction. Aß oligomer stereotactic injection model was established to explain the relationship between Aß and vasculopathy. Immunofluorescence staining, western blot, and real-time PCR were applied to detect the morphological and molecular alternations of pericytes. Primary cultured pericytes and bEnd.3 cells were employed to explore the underlying mechanisms. RESULTS: Vasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Aß-injected model, suggesting a direct relationship between Aß and vascular dysfunction. Pericytes showed impaired features including low PDGFRß expression and increased pro-inflammatory chemokines secretion under the administration of Aß in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency. CONCLUSIONS: Our results provide new insights into the pathogenic mechanism underlying Aß-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.