Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

LGR5/GPR49 is implicated in motor neuron specification in nervous system.

The biological roles of stem cell marker LGR5, the receptor for the Wnt-agonistic R-spondins, for nervous system are poorly known. Bioinformatics analysis in normal human brain tissues revealed that LGR5 is closely related with neuron development and functions. Interestingly, LGR5 and its ligands R-spondins (RSPO2 and RSPO3) are specifically highly expressed in projection motor neurons in the spinal cord, brain stem and cerebral. Inhibition of Notch activity in neural stem cells (NSCs) increased the percentage of neuronal cells and promoted LGR5 expression, while activation of Notch signal decreased neuronal cells and inhibited the LGR5 expression. Furthermore, knockdown of LGR5 inhibited the expression of neuronal markers MAP2, NeuN, GAP43, SYP and CHRM3, and also reduced the expression of genes that program the identity of motor neurons, including Isl1, Lhx3, PHOX2A, TBX20 and NEUROG2. Our data demonstrated that LGR5 is highly expressed in motor neurons in nervous system and is involved in their development by regulating transcription factors that program motor neuron identity.

LGR5 is a proneural factor and is regulated by OLIG2 in glioma stem-like cells.

The biological functional roles of LGR5 (leucine-rich repeat containing G protein-coupled receptor 5, also known as GPR49), a novel potential marker for stem-like cells in glioblastoma (GSCs), is poorly acknowledged. Here, we demonstrated that LGR5 was detected in glioblastoma tissues and GSCs. Bioinformatics analysis revealed that LGR5 is closely related to neurogenesis and neuronal functions, and preferentially expressed in Proneural subtype of GBMs. Furthermore, LGR5 is regulated by Proneural factor OLIG2, which is important for both neurogenesis and GSC maintenance. Biological experiments in GSC cells validated the bioinformatics analysis results and revealed that LGR5 regulated the tumor sphere formation capacity, an important stem cell property for GSCs. Therefore, LGR5 expression may be functionally correlated with the neurogenic competence, and be regulated by OLIG2 in GSCs.

CDH5 is specifically activated in glioblastoma stemlike cells and contributes to vasculogenic mimicry induced by hypoxia.

BACKGROUND: A proportion of glioblastoma stemlike cells (GSCs) expressing endothelial cell marker CDH5 (vascular-endothelial-cadherin or CD144) can transdifferentiate into endothelial cells and form blood vessels. However, the implications of CDH5 expression in gliomas and how it is regulated in GSCs remain to be clarified. METHODS: The mRNA and protein levels of CDH5 were detected in glioma samples and cultured cell lines, and the prognostic value of the CDH5 expression level for GBM patients was evaluated. Bioinformatics analysis was performed to reveal the potential functional roles of CDH5 in glioblastoma multiforme. Gene knockdown induced by short hairpin RNA, chromatin immunoprecipitation analysis, and a vasculogenic tube formation assay were performed to investigate the relationships among hypoxia, CDH5 expression level, and angiogenesis. RESULTS: CDH5 was overexpressed in gliomas, correlated with tumor grades, and was an independent adverse prognostic predictor for glioblastoma multiforme patients. CDH5 was specifically activated in GSCs but not in non-GSCs or neural stem cells, and CDH5(+) cells could produce xenografts in immunocompromised mice. Bioinformatics analysis demonstrated that CDH5 might interact directly with hypoxia-inducible factor (HIF)2α. CDH5 expression was significantly upregulated in GSCs, but not in non-GSCs or normal neural stem cells, under a 1% O2 condition. Both HIF1α and HIF2α positively regulated CDH5 level in GSCs and could bind to the promoter of CDH5. Furthermore, CDH5 contributed to the vasculogenic mimicry of GSCs, especially under hypoxic conditions. CONCLUSIONS: The specific expression of CDH5 in GSCs may contribute to GSC-derived neovasculogenesis in glioblastoma multiforme, especially under hypoxic conditions, revealing novel tumorigenic mechanisms contributed by GSCs.

Endoscopic endonasal transsphenoidal surgery for invasive pituitary adenoma.

Invasive pituitary adenomas (IPA) involving the skull base extend from the sella region, and invade surrounding structures. In the present study, we reviewed the therapeutic efficacy in a group of patients with IPA treated with endoscopic endonasal transsphenoidal surgery. Data from 78 IPA patients at our hospital were retrospectively reviewed. The diagnostic modalities, surgical techniques, and outcomes were reviewed. Diagnosis was confirmed by endocrinological profile and CT or MRI in all patients. Surgery was performed via an endoscopic endonasal transsphenoidal approach. Thirty-five patients (44.9%) had hormonally active tumors, and 43 (55.1%) had nonfunctioning tumors. Complete removal of the tumor was achieved in 62 patients (79.5%) and subtotal removal in 12 (15.4%); partial removal was achieved in the remaining four patients (5.1%) who had fibrous or dumbbell-shaped adenomas. The mean follow-up was 43.2 months in 65 patients and the clinical symptoms in all patients improved to varying degrees. In 52 patients, the tumors completely disappeared on follow-up imaging. Visual symptoms improved in 96.4% of the patients who had presented with visual impairment. These surgical results show that endoscopic endonasal transsphenoidal surgery for resection of IPA has advantages. We suggest that the endoscopic endonasal transsphenoidal surgery method is a safe, minimally invasive and efficient surgical technique for removal of IPA, providing good visualization of the operative field, generally complete tumor removal, short procedure duration, and minimal postoperative complications.

Emergency transsphenoidal surgery for hemorrhagic pituitary adenomas.

Hemorrhagic pituitary adenoma (HPA) is an acute clinical event in neurosurgery. Emergency surgical decompression is the most effective treatment. We retrospectively reviewed 65 cases collected from the Xijing Institute of Clinical Neuroscience from 1995 to 2005 with HPA. The majority of the patients (81.5%) experienced the acute symptoms of pituitary apoplexy including headache, ocular paresis, visual field deficits and hypopituitarism. On imaging features, 34 adenomas (52.3%) showed marked suprasellar extension, 17 (26.2%) showed moderate extension, and 6 (9.2%) had slight extension, another eight (12.3%) were intrasellar. All patients were treated promptly by emergency surgical decompression usually within 24h after the hospitalization. Twenty four patients operated on by the traditional transsphenoidal microsurgery; whereas 41 patients operated on by the endoscopic endonasal transsphenoidal surgery. Total removal of tumors was achieved in 59 cases (90.8%) and subtotal removal in 6 cases (9.2%). Postoperative radiotherapy, suppressive drug therapy and endocrine replacement therapy were required in seven patients with either remaining tumor or tumor recurrence. In a median follow-up period of 49 months for 54 cases, most patients' clinical symptoms had markedly improved. Visual acuity and visual fields improved in 88.4% and 92.7% of the patients who had preoperative visual symptoms, respectively. The majority of the HPA often occurred in patients with macroadenomas. With emergency surgical treatment, most patients with HPA could have quick improvement of symptoms, especially for altered consciousness and visual acuity or visual fields impairments.

[Endoscopic endonasal transsphenoidal approach for pituitary adenomas].

OBJECTIVE: To assess the clinical curative effect of the endonasal transsphenoidal approach for removing pituitary adenoma (PA) under neuroendoscope-assisted. METHODS: There were 215 patients who had undergone neuroendoscopic transsphenoidal surgery. Each patient received CT or MRI examination which showed the size and surrounding structural of tumor. RESULTS: Among the 215 patients, 190 cases (88.4%) had total removal, 17 cases (7.9%) achieved subtotal removal and the remaining 8 cases (3.7%) with fibrous tumor was carried out partial removal. Two patients (0.9%) died after operation. Postoperative follow-up period was 1 to 10 months (the average was 3.5 months). In 182 patients, 150 cases (90.9%) got vision recovered rapidly compared with their preoperative symptoms, such as diminished acuities and visual field defects, and 15 cases (9.1%) had gotten improvements to some extend among 165 who diagnosed as pituitary macroadenoma (PMaA); There were 17 patients who diagnosed as microadenoma (PMiA) showed that the pituitary dyshormonism recovered gradually. CONCLUSIONS: The endonasal transsphenoidal surgery under the neuroendoscope-assisted appears to be a safe, effective and micro-invasive method for PA.

cDNA microarray reveals signaling pathways involved in hormones expression of human pituitary.

Pituitary, a master gland of neuroendocrine system, secretes hormones that orchestrate many physiological processes, under the regulation of multiple signaling pathways. To investigate the genes involved in hormones expression of human pituitary, homemade cDNA microarray containing 14,800 human genes/ESTs were used to profile the gene expression in both fetal and adult pituitaries. Seven hundred and twelve known genes changed over 2-fold between the both tissues. Of which, 23 genes were changed with hormones expression in aging were confirmed by RT-PCR, not only the known regulators such as Pit1, GATA4, ESRRA, GABA-A, and EMK, but also LOC55884, DUSP3, PNN, and RCL, which had not been reported to be involved in the hormones expression. Correspondingly, the mRNAs of GH, PRL, POMC, TSH-beta, FSH-beta, and LH-beta, was increased as much as 6- to 20-fold in adult pituitary than those in fetal pituitary, by real-time quantitative RT-PCR assay. In addition, the mRNAs of signaling pathways, such as cAMP-PKA-CREB, PI3K-Akt, and PKA-ERK were further investigated. Of them, it was only cAMP-PKA-CREB pathway, but not PI3K-Akt and PKA-ERK have the same expressing pattern as hormones. It suggested that cDNA microarray is highly advantages to profile the differential expressed genes that were involved in hormones expression of human pituitary, but it might ignore some responding proteins regulated posttranscriptionally.

[Comparison of the intracranial pressure value in patients with hypertensive intracerebral hemorrhage treated with traditional craniotomy and puncture drainage].

OBJECTIVE: To compare the difference of intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage (HICH) treated with two surgical procedures, traditional craniotomy and puncture drainage. METHODS: One hundred and twelve cases with HICH were randomly divided into two groups. In one group, 60 patients were operated by traditional craniotomy and in another group, 52 cases by puncture drainage and urokinase treatment. In the meantime, ICP was monitored by placing catheter in lateral ventricle on the contralateral side of the hemorrhage. ICP values were recorded after operation at once, at 24 hours, 72 hours and 1 week. RESULTS: Although all the patients showed increased ICP, the increasing degree in patients treated with traditional craniotomy had lower ICP values (P<0.05 or P<0.01). CONCLUSION: Traditional craniotomy has advantages over puncture drainage for patients with HICH at least with respect to decreasing ICP.

[Analysis of the results of 143 cases of pituitary micro-adenoma treated by Linac X-Knife stereotactic radioneurosurgery].

BACKGROUND & OBJECTIVE: The trans-sphenoid surgery was one of the main methods for the treatment of functional pituitary micro-adenoma for many years, while the development of radiosurgical techniques in recent years has given neurosurgeons new ways to treat functional pituitary micro-adenoma. This report aimed to ascertain the effectiveness of X-Knife stereotactic radioneurosurgery on pituitary micro-adenoma. METHODS: From June 1996 to June 2001, 143 cases of functional pituitary micro-adenoma were treated by X-Knife radiosurgery, in which 73 cases of secreting prolactin (PRL),54 cases of secreting growth hormone(GH), 13 cases of secreting adrenal corticotrophin hormone (ACTH), and 3 cases of secreting both PRL and GH. The radiosurgical procedure included local anesthesia administration, head-ring mounting, serial thin slice CT scanning with contrast enhancement, CT image transfer, treatment planning on the computer workstation, stereotactic localization of the target onto the Linac isocenter, and then the Linac was used to perform multiple non-coplannar arc radiation. All cases received single fraction radiosurgery. RESULTS: After X-Knife radiosurgery, follow-up ranged 3-60 months (median 38.4 month). Among those 112 cases that acquired follow-up, 78(69.7%) cases showed good clinical improvements, 10(8.9%) cases showed relatively good clinical improvements, 19(16.8%) cases showed no clinical improvement, and 5(4.6%) cases had progression of disease and enlargement of the adenoma. CONCLUSION: X-Knife radiosurgery is a safe and effective technique for the treatment of functional pituitary micro-adenoma. While for young patients, the diagnosis of pituitary micro-adenoma and use of X-Knife radiosurgery should be very cautious, otherwise hypopituitarism might be resulted.

Brain metastasis: experience of the Xi-Jing hospital.

BACKGROUND: The management of metastatic brain tumors is an important issue in patients with malignant tumors or cancer. The authors summarize the results of patients with brain metastases treated at the Xi-Jing Hospital during a 10-year period, in order to assess the best modality of treatment for patients with brain metastases. METHODS: Between 1990 and 2000, 463 patients with brain-metastatic tumors were treated at the Xi-Jing Hospital of the Fourth Military Medical University, Xian, China. In most patients, the pathologic diagnosis of primary cancer was obtained before they were referred for their brain metastasis. There were 34 (8.42%) cases with an unknown primary cancer site at the time of initial presentation. Patients were grouped according to treatment methods, which included neurosurgical craniotomy (NS; 130 patients), whole-brain radiotherapy (WBRT; 120 patients). Linac XKnife radiosurgery (RS; 130 patients) and Linac XKnife radiosurgery plus WBRT (RT; 83 cases). Survival was measured from the time of treatment and was analyzed by the Kaplan-Meier product-limit method and then plotted. Differences between curves were evaluated using the log-rank test. Multivariate factors associated with survival were analyzed using the Cox proportional hazards model. RESULTS: The survival time was 68.4 +/- 7.20 weeks after NS, 51.3 +/- 5.04 weeks after WBRT, 67.9 +/- 3.68 weeks after RS and 89.7 +/- 4.50 weeks after RT. The presence of active systemic cancer in a larger number of metastatic tumors was associated with a poor survival (p = 0.0003 and 0.0000). The female patients showed better survival rates over the male ones (p = 0.0000). Patients treated with RT had a better survival than those treated with NS, WBRT and RS (p = 0.0048, 0.0000 and 0.1222, respectively), although the latter did not show statistical significance. CONCLUSIONS: RS was an effective modality for patients with brain metastases, and if combined with WBRT, survival was better. Progression of systemic cancer and the number of metastatic tumors were the most significant factors for a poor survival after treatment of the brain metastases.