Early diagnosis of intracranial atherosclerotic large vascular occlusion: A prediction model based on DIRECT-MT data.

Aims: This study aimed to build a prediction model to early diagnose intracranial atherosclerosis (ICAS)-related large vascular occlusion (LVO) in acute ischemic stroke patients before digital subtractive angiography. Methods: Patients enrolled in the DIRECT-MT trial (NCT03469206) were included in our secondary analysis and distributed into ICAS-LVO and non-ICAS-LVO groups. We also retrieved demographic data, medical histories, clinical characteristics, and pre-operative imaging data. Hypothesis testing was used to compare data of the two groups, and univariate logistic regression was used to identify the predictors of ICAS-LVO primarily. Then, we used multivariate logistic regression to determine the independent predictors and formulate the prediction model. Model efficacy was estimated by the area under the receiver operating characteristic (ROC) curve (AUC) and diagnostic parameters generated from internal and external validations. Results: The subgroup analysis included 45 cases in the ICAS-LVO group and 611 cases in the non-ICAS-LVO group. Variates with p < 0.1 in the comparative analysis were used as inputs in the univariate logistic regression. Next, variates with p < 0.1 in the univariate logistic regression were used as inputs in the multivariate logistic regression. The multivariate logistic regression indicated that the atrial fibrillation history, hypertension and smoking, occlusion located at the proximal M1 and M2, hyperdense artery sign, and clot burden score were related to the diagnosis of ICAS-LVO. Then, we constructed a prediction model based on multivariate logistics regression. The sensitivity and specificity of the model were 84.09 and 74.54% in internal validation and 73.11 and 71.53% in external validation. Conclusion: Our current prediction model based on clinical data of patients from the DIRECT-MT trial might be a promising tool for predicting ICAS-LVO.

Association of Famine Exposure on the Changing Clinical Phenotypes of Primary Hyperparathyroidism in 20 years.

Background & Aims: Primary hyperparathyroidism(PHPT) has been evolving into a milder asymptomatic disease. No study has assessed the association between famine exposure and such a shift. We aim to explore the effects of China's Great Famine exposure on the changing pattern of PHPT phenotypes. Methods: 750 PHPT patients diagnosed from 2000 to 2019 were studied. The clinical presentations were compared between them in recent 10 years (2010-2019) and previous 10 years (2000-2009). Participants were then categorized into fetal, childhood, adolescent, adult exposure, and unexposed groups. Logistic regression was used to estimate the odds ratios (ORs) and confidence intervals (CIs) of famine exposure as factors contributing to the changes in the clinical presentations of PHPT. Results: Serum levels of PTH, albumin-corrected Ca, tumor size, eGFR, BMDs (all P<0.001), and clinical symptoms became milder in recent 10 years. Famine exposure (72.6% vs 58.4%, P<0.001), especially the adult exposure (18.8% vs 4.1%, P<0.001)was significant less in recent 10 years. The ORs (95%CIs) of having upper 3rd tertile PTH were 2.79(1.34,5.8), 2.07(1.04,4.11), 3.10(1.15,8.38) and 8.85(2.56,30.56) for patients with fetal, childhood, adolescent and adult famine exposure, respectively. The ORs (95%CIs) of upper 3rd tertile albumin-corrected Ca and upper 3rd tertile of tumor size was 4.78(1.39, 16.38) and 4.07(1.12,14.84) for participants with adult famine exposure, respectively. All these associations were independent of age, sex, disease duration and other confounders. Conclusions: The clinical manifestations of PHPT in China continue to be milder. Exposure to famine is associated with PHPT. Less famine exposure might be responsible for the mile form of PHPT in recent years.

Multidisciplinary team efforts to improve the pregnancy outcome of pregnancy complicated with primary hyperparathyroidism: case series from a single hospital.

BACKGROUND: There is no consensus or management algorithm for primary hyperparathyroidism (PHPT) in pregnancy. METHODS: This study comprises a retrospective case series. From August 2014 to December 2020, 9 cases of PHPT in pregnancy were diagnosed by a multidisciplinary team (MDT) consultation center of obstetrics in our hospital. Their clinical manifestations, treatment strategies, and maternal and infant outcomes were analyzed. RESULTS: The median onset age of the patients was 32 (25 ~ 38) years. PHPT was diagnosed in two cases before pregnancy, in six cases during pregnancy and in one case postpartum. The main clinical manifestations were nausea, vomiting, and other nonspecific symptoms, with anemia as the most common maternal complication. Hypercalcemia crisis was developed in one case. The median levels of preoperative serum calcium and parathyroid hormone (PTH) were 3.08 (2.77 ~ 4.21) mmol/L and 300.40 (108.80 ~ 2603.60) pg/ml, respectively. The parathyroid ultrasonography tests were positive in eight cases and negative in one patient who had an ectopic lesion localized by 99mTc-MIBI. Parathyroidectomy was conducted in 7 cases during the 2nd trimester, including 2 patients diagnosed before pregnancy who refused surgery, 1 patient during the 1st trimester, and 1 patient postpartum, with a significant reduction in serum concentrations of calcium and PTH. A management algorithm was developed. CONCLUSION: This case series suggests that pregnant women with PHPT should be managed by MDT according to the algorithm. If PHPT is confirmed in fertile women before pregnancy, parathyroidectomy should be strongly suggested and performed. If PHPT is diagnosed during pregnancy, even in its mild form, surgical treatment, optimally during the 2nd trimester, is effective and safe for pregnancy and neonatal outcome.

Lgr4 promotes aerobic glycolysis and differentiation in osteoblasts via the canonical Wnt/ß-catenin pathway.

Lgr4, a G-protein-coupled receptor, is associated with various physiological and pathological processes including oncogenesis, energy metabolism, and bone remodeling. However, whether Lgr4 is involved in osteoblasts' metabolism is not clear. Here we uncover that in preosteoblast cell line, lacking Lgr4 results in decreased osteogenic function along with reduced glucose consumption, glucose uptake, and lactate production in the presence of abundant oxygen, which is referred to as aerobic glycolysis. Activating canonical Wnt/ß-catenin signaling rescued the glycolytic dysfunction. Lgr4 promotes the expression of pyruvate dehydrogenase kinase 1 (pdk1) and is abolished by interfering canonical Wnt/ß-catenin signaling. Mice lacking Lgr4 specifically in osteoblasts (Lgr4osb-/- ) exhibit decreased bone mass and strength due to reduced bone formation. Additionally, glycolysis of osteoblasts is impaired in Lgr4osb-/- mice. Our study reveals a novel function of Lgr4 in regulating the cellular metabolism of osteoblasts. © 2021 American Society for Bone and Mineral Research (ASBMR).

Network pharmacology study on the mechanism of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel for anxiety disorders.

BACKGROUND: Although anxiety disorders are one of the most common mental illness in population, antianxiety drugs often only have single action targets, require long-term use, and are associated with many adverse reactions and dependencies. Professor Yan Zhaojun from Shandong Provincial Hospital of Traditional Chinese Medicine (TCM) has applied the modified Renshu Powder, a TCM formula, to treat anxiety disorders, with satisfactory outcomes. Here, we investigated the mechanism of action of two core herbs (prepared Rehmannia root and Chinese arborvitae kernel) in the Renshu Powder in the treatment of anxiety disorders by using network pharmacology approaches. METHODS: Candidate compounds of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel were extracted via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. The targets of action of the main compounds were collected using the SwissTargetPrediction database. Targets associated with anxiety disorders were retrieved from DisGeNET, Online Mendelian Inheritance in Man (OMIM), DrugBank, GeneCards, and Comparative Toxicogenomics Database (CTD) databases. The compound-target interaction network was constructed by Cytoscape 3.7.2 software, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses the data by using Metascape. RESULTS: The main active compounds of the herb pair included arachidonic acid, stigmasterol, and beta-sitosterol. The key targets included Nitric Oxide Synthase 3 (NOS3), Epidermal growth factor (EGF), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Caspase 3 (CASP3), Mitogen-Activated Protein Kinase 1 (MAPK1), Peroxisome proliferator-activated receptor gamma (PPARG), RELA Proto-Oncogene, NF-KB Subunit (RELA), Estrogen Receptor 1 (ESR1), Solute Carrier Family 6 Member 4 (SLC6A4), and Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN). Anxiety disorder-related GO analysis mainly involved synaptic signaling, neurotransmitter receptor activity, and G protein-coupled neurotransmitter receptor activity. The KEGG pathways involved neuroactive ligand-receptor interaction, serotonergic synapse, PI3K/AKT/mTOR signaling pathway, and MAPK signaling pathway. CONCLUSIONS: The mechanism of action of the prepared Rehmannia root-Chinese arborvitae kernel in treating anxiety disorders involves multiple ingredients, multiple targets, and pathways.

Centromere protein U enhances the progression of bladder cancer by promoting mitochondrial ribosomal protein s28 expression.

Bladder cancer is one of the most common types of cancer. Most gene mutations related to bladder cancer are dominantly acquired gene mutations and are not inherited. Previous comparative transcriptome analysis of urinary bladder cancer and control samples has revealed a set of genes that may play a role in tumor progression. Here we set out to investigate further the expression of two candidate genes, centromere protein U (CENPU) and mitochondrial ribosomal protein s28 (MRPS28) to better understand their role in bladder cancer pathogenesis. Our results confirmed that CENPU is up-regulated in human bladder cancer tissues at mRNA and protein levels. Gain-of-function and loss-of-function studies in T24 human urinary bladder cancer cell line revealed a hierarchical relationship between CENPU and MRPS28 in the regulation of cell viability, migration and invasion activity. CENPU expression was also up-regulated in in vivo nude mice xenograft model of bladder cancer and mice overexpressing CENPU had significantly higher tumor volume. In summary, our findings identify CENPU and MRPS28 in the molecular pathogenesis of bladder cancer and suggest that CENPU enhances the progression of bladder cancer by promoting MRPS28 expression.

Higher Baseline Cortical Score Predicts Good Outcome in Patients With Low Alberta Stroke Program Early Computed Tomography Score Treated with Endovascular Treatment.

BACKGROUND: Patients with large vessel occlusion and noncontrast computed tomography (CT) Alberta Stroke Program Early CT Score (ASPECTS) <6 may benefit from endovascular treatment (EVT). There is uncertainty about who will benefit from it. OBJECTIVE: To explore the predicting factors for good outcome in patients with ASPECTS <6 treated with EVT. METHODS: We retrospectively reviewed 60 patients with ASPECTS <6 treated with EVT in our center between March 2018 and June 2019. Patients were divided into 2 groups because of the modified Rankin Score (mRS) at 90 d: good outcome group (mRS 0-2) and poor outcome group (mRS ≥3). Baseline and procedural characteristics were collected for unilateral variate and multivariate regression analyses to explore the influent variates for good outcome. RESULTS: Good outcome (mRS 0-2) was achieved in 24 (40%) patients after EVT and mortality was 20% for 90 d. Compared with the poor outcome group, higher baseline cortical ASPECTS (c-ASPECTS), lower intracranial hemorrhage, and malignant brain edema after thrombectomy were noted in the good outcome group (all P < .01). Multivariate logistic regression showed that only baseline c-ASPECTS (≥3) was positive factor for good outcome (odds ratio = 4.29; 95% CI, 1.21-15.20; P = .024). The receiver operating characteristics curve indicated a moderate value of c-ASPECTS for predicting good outcome, with the area under receiver operating characteristics curve 0.70 (95% CI, 0.56-0.83; P = .011). CONCLUSION: Higher baseline c-ASPECTS was a predictor for good clinical outcome in patients with ASPECTS <6 treated with EVT, which could be helpful to treatment decision.

Tim-3 Expression and MGMT Methylation Status Association With Survival in Glioblastoma.

BACKGROUND: A profound understanding of the molecular landscape of glioblastoma multiforme (GBM) will make it possible to develop better and more intelligent therapies directed toward specific molecular targets and may one day yield better prognostic capabilities. Immune checkpoint molecules have inspired the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecule T cell immunoglobulin mucin-3 (Tim-3) on tumor-infiltrating immune cells (TIICs) and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status has not yet been fully elucidated. We aimed to develop an MGMT promoter methylation status-associated immune prognostic signature for GBM. PATIENTS AND METHODS: A total of 84 patients with newly diagnosed GBM were included in this study. MGMT promoter methylation status was retrospectively analyzed, and the expression level of Tim-3 was investigated using immunohistochemistry (IHC). The correlation between Tim-3 expression combined with MGMT promoter methylation status and prognosis was explored. RESULTS: Tim-3 expression varied in GBM patients. Mesenchymal expression of Tim-3 in GBM tissues was present 73.81% (62/84) of patients, and these were subdivided into groups based on low 15.48% (13/84), moderate 7.14% (6/84), or strong expression 51.19% (43/84). Forty-eight patients had tumors that tested positive for MGMT promoter methylation, while the remaining 36 patients tested negative. CONCLUSIONS: We profiled the immune status of MGMT promoter methylation in GBM and established a local immune signature for GBM that could independently identify patients with a favorable prognosis, indicating a relationship between prognosis and GBM immune signature. MGMT promoter methylation with lower Tim-3 expression was significantly associated with better survival.

BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling.

Bone remodeling is dynamic and is tightly regulated through bone resorption dominated by osteoclasts and bone formation dominated by osteoblasts. Imbalances in this process can cause various pathological conditions, such as osteoporosis. Bone morphogenetic protein 9 (BMP9), a biomolecule produced and secreted by the liver, has many pharmacological effects, including anti-liver fibrosis, antitumor, anti-heart failure, and antidiabetic activities. However, the effects of BMP9 on the regulation of osteoblast and osteoclast functions and the underlying molecular mechanism(s) have not yet been investigated. In this study, BMP9 increased the expression of osteoblastogenic gene markers, such as ALP, Cola1, OCN, RUNX2, and OSX, and ALP activity in MC3T3-E1 cells by upregulating LGR6 and activating the Wnt/ß-catenin pathway. BMP9 also suppressed receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation of bone marrow macrophages (BMMs) by inhibiting the Akt-NF-κB-NFATc1 pathway. More importantly, in an ovariectomy (OVX) mouse model, BMP9 attenuated bone loss and improved bone biomechanical properties in vivo by increasing bone-forming activity and suppressing bone resorption activity. Accordingly, our current work highlights the dual regulatory effects that BMP9 exerts on bone remodeling by promoting bone anabolic activity and inhibiting osteoclast differentiation in OVX mice. © 2020 American Society for Bone and Mineral Research.

Tim-3 expression in glioma cells is associated with drug resistance.

OBJECTIVE: T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) has been widely recognized as a negative regulator of antitumor immunity. However, the mechanism by which Tim-3 suppresses antitumor treatment in gliomas remains unclear. This study aims to explore whether Tim-3 is expressed and to evaluate its effect in drug-fasted glioma cells. SUBJECTS AND METHODS: U87 and U251 glioma cell lines were tested. Cell proliferation activity, cell viability, and the protein and mRNA levels of Tim-3 were detected using CCK-8, flow cytometry, Western blotting, and reverse transcription-quantitative polymerase chain reaction, respectively. Enhancement of the sensitivity of glioma cells to chemotherapeutic agents was tested after inhibiting Tim-3 expression using Tim-3 small interfering RNAs (siRNA). RESULTS: As temozolomide (TMZ) concentration increased, the ratio of apoptotic cells also increased accordingly. However, the level of Tim-3 expression in living cells from the high-dose group was higher than in the low- and middle-dose groups. After interfering with the expression of Tim-3 using siRNA against Tim-3, the killing effect of TMZ rose through an increase in apoptosis. CONCLUSIONS: The presence of Tim-3 mRNA and protein in glioma cells was detected. Significantly, knocking down Tim-3 expression improved the potential of TMZ treatment.

Stent Angioplasty for Acute Intracranial Atherosclerotic Occlusion After Failed Thrombectomy: A Single-Institution Series of 55 Patients.

INTRODUCTION: Analysis of safety and effectiveness of stent angioplasty for failure of thrombectomy in patients with acute intracranial atherosclerotic occlusion. METHODS: Retrospective continuous analysis of the clinical data of 458 patients with acute stroke undergoing endovascular artery thrombectomy in Changhai Hospital of Second Military Medical University from May 2013 to February 2018. Patients with acute intracranial atherosclerotic occlusion treating with stent implantation were included and the safety and effectiveness of stent angioplasty was evaluated. RESULTS: There was successful stent release in 55 patients. There were 36 cases (65.5%) with occlusion located in the anterior circulation and 19 cases (34.5%) in the posterior circulation. Twenty patients underwent intravenous thrombolysis before surgery, and the time of admission to intravenous thrombolysis was (39.9 ± 13.2) minutes. Fifty-four patients (98.2%) achieved modified thrombolysis in cerebral infarction 2b-3 recanalization. The National Institutes of Health Stroke Scale score 2.0 (0.0,6.0) 7 days after surgery was significantly improved compared with the preoperative National Institutes of Health Stroke Scale score 12.5 (6.0-20.0) (Z = -4.073, P < 0.05). Intracranial hemorrhage occurred in 7 patients (12.7%) after surgery, among them, symptomatic intracranial hemorrhage occurred in 2 cases (3.6%). CTP examination of the skull 3-5 days after operation showed: Among 39 cases (70.9%): 33 cases (84.6%) were patency, 4 cases (10.3%) were occlusion, 2 cases (5.1%) were moderate stenosis, and 16 cases (29.1%) were not examined by computed tomography perfusion. Ninety-day follow-up showed that a total of 43 cases were followed up, and 12 cases were lost to follow-up. Thirty-four patients (79.1%) had a good prognosis 90 days after surgery (modified Rankin scale score 0-2) and 9 patients died (20.9%). CONCLUSION: When thrombectomy in patients with acute intracranial atherosclerotic occlusion fails, stent angioplasty is safe and effective; however, short-term stent reocclusion after surgery cannot be ignored. Because of the small sample size, larger multicenter clinical studies are needed to confirm this result.

PITUITARY STALK THICKENING IN A LARGE COHORT: TOWARD MORE ACCURATE PREDICTORS OF PITUITARY DYSFUNCTION AND ETIOLOGY.

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins. Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed. Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio [OR], 3.57; P<.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes. Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated. Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width.

The browning of white adipose tissue and body weight loss in primary hyperparathyroidism.

BACKGROUND: Parathyroid hormone related protein (PTHrP) triggers white adipose tissue (WAT) browning and cachexia in lung cancer mouse models. It remains unknown whether excessive PTH secretion affects WAT browning and to what extent it contributes to body weight change in primary hyperparathyroidism (PHPT). METHODS: Using the adeno-associated virus injection, Pth gene over-expressed mice mimicking PHPT were firstly established to observe their WAT browning and body weight alteration. The association between PTH and body weight was investigated in 496 PHPT patients. The adipose browning activities of 20 PHPT and 60 control subjects were measured with PET/CT scanning. FINDINGS: Elevated plasma PTH triggered adipose tissue browning, leading to increased energy expenditure, reduced fat content, and finally decreased body weight in PHPT mice. Higher circulating PTH levels were associated with lower body weight (ß = -0.048, P = .0003) independent of renal function, serum calcium, phosphorus,and albumin levels in PHPT patients. PHPT patients exhibited both higher prevalence of detectable brown/beige adipose tissue (20% vs 3.3%, P = .03) and increased browning activities (SUV in cervical adipose was 0.77 vs 0.49,P = .02) compared with control subjects. INTERPRETATION: Elevated serum PTH drove WAT browning program, which contributed in part to body weight loss in both PHPT mice and patients. These results give insights into the novel pathological effect of PTH and are of importance in understanding the metabolic changes of PHPT. FUND: This research is supported by the National Key Research and Development Program of China and National Natural Science Foundation of China.

Adenovirus-Mediated CRM197 Sensitizes Human Glioma Cells to Gemcitabine by the Mitochondrial Pathway.

PURPOSE: The cross-reacting material 197 (CRM197) is a mutation of the diphtheria toxin. The protein of CRM197 was used successfully for the therapy of various tumors in the recent studies. In this study, the recombinant adenoviruses containing the CRM197gene(AdCRM197) were used to enhance the cellar toxicity of gemcitabine in human glioma U87, U251, and H4 cells. PROCEDURES: MTT assay and flow cytometric analysis were performed to test the apoptosis of the U87, U251 and H4 cells with the combined treatment of AdCRM197 plus gemcitabine. Western blotting analyses were carried out to detect the cell apoptosis of the mitochondrial pathway. And the xenograft nude mice were used to observe the enhanced antitumor effect of AdCRM197 in vivo. RESULTS: AdCRM197 sensitizes human glioma cells to gemcitabine in vitro by the mitochondrial pathway. Tumor volume was inhibited and survival time was prolonged in the U251 or U87 xenografted nude mice with gemcitabine plus AdCRM197. The enhanced antitumor effect of AdCRM197 was also detected by the immunohistochemical analyses and TUNEL staining. CONCLUSION: The authors found that AdCRM197 sensitized the human glioma to gemcitabine not only in vitro but also in vivo. They provide the first evidence that adenovirus-mediated CRM197 may be a potential chemosensitizing agent for the treatment of cancer. The diphtheria toxin is of great toxicity that even one molecule of diphtheria toxin is enough to kill one cell. However, because of the high toxicity, the diphtheria toxin would kill the packing cells when it is being packaged into the recombinant viruses. Therefore, the diphtheria toxin is hard to be used in the gene therapy for virus vectors. The cross-reacting material 197 (CRM197) is a mutation of the diphtheria toxin. Unlike DTA, CRM197 exhibit a weak toxicity. The week toxicity of CRM197 is a good feature for the virus packaging. In the present study, we used a recombinant adenovirus which carried a CRM197 gene (AdCRM197) to enhance the cellar toxicity of gemcitabine in human glioma cells.

Bone: Another potential target to treat, prevent and predict diabetes.

Type 2 diabetes mellitus is now a worldwide health problem with increasing prevalence. Mounting efforts have been made to treat, prevent and predict this chronic disease. In recent years, increasing evidence from mice and clinical studies suggests that bone-derived molecules modulate glucose metabolism. This review aims to summarize our current understanding of the interplay between bone and glucose metabolism and to highlight potential new means of therapeutic intervention. The first molecule recognized as a link between bone and glucose metabolism is osteocalcin (OCN), which functions in its active form, that is, undercarboxylated OCN (ucOC). ucOC acts in promoting insulin expression and secretion, facilitating insulin sensitivity, and favouring glucose and fatty acid uptake and utilization. A second bone-derived molecule, lipocalin2, functions in suppressing appetite in mice through its action on the hypothalamus. Osteocytes, the most abundant cells in bone matrix, are suggested to act on the browning of white adipose tissue and energy expenditure through secretion of bone morphogenetic protein 7 and sclerostin. The involvement of bone resorption in glucose homeostasis has also been examined. However, there is evidence indicating the implication of the receptor activator of nuclear factor κ-B ligand, neuropeptide Y, and other known and unidentified bone-derived factors that function in glucose homeostasis. We summarize recent advances and the rationale for treating, preventing and predicting diabetes by skeleton intervention.

The relationship among serum lipocalin 2, bone turnover markers, and bone mineral density in outpatient women.

PURPOSE: We aimed to investigate associations among serum levels of LCN2, bone resorption marker carboxy-terminal cross-linking telopeptide of type-1 collagen (CTx), bone formation marker osteocalcin (OCN), and bone mineral densities (BMDs) in ambulatory healthy women. METHODS: This cross-sectional study analyzed 1012 previously enrolled outpatient Han Chinese women. BMDs of the lumbar spine and femoral neck were measured using dual energy X-ray absorptiometry. Serum levels of LCN2, CTx, OCN, and creatinine (Scr) were measured. RESULTS: Circulating LCN2 was inversely correlated with BMDs at the lumbar spine and femoral neck (Spearman's r = -0.08, P = 0.010 and r = -0.14, P < 0.001; respectively). A significant positive correlation between LCN2 and CTx (r = 0.11, P < 0.001), OCN (r = 0.06, P = 0.047), age (r = 0.21, P < 0.001), and Scr (r = 0.24, P < 0.001) was also observed. After adjusting for age and Scr, the correlation among LCN2, BMDs and OCN disappeared, but LCN2 was still positively associated with CTx (r = 0.08, P = 0.010). The circulating concentration of LCN2 showed no significant difference between subjects with and without osteoporotic fractures (43.63 (35.29, 53.66) vs. 42.25 (34.43, 51.46) ng/ml, respectively, P = 0.111). Serum CTx concentrations rose with serum LCN2 increasing from the lowest to the highest quartile (P for trend = 0.005), even after adjusting for age and Scr (P for trend = 0.040). In multivariate regression analysis, LCN2 was one of the main determinants for changes in serum CTx (standard ß = 0.061, P = 0.005). CONCLUSIONS: In ambulatory healthy women, the relationships among serum LCN2 level, BMDs, and OCN were confounded by age and Scr. Although LCN2 was positively related with CTx, the correlation was very weak and may not be physiologically relevant.

Postoperative functional status in patients with supratentorial superficial low-grade glioma.

BACKGROUND: We investigated the functional status of adult supratentorial superficial low-grade glioma (ASS-LGG) after surgery and analyzed its relevant factors to guide the therapeutic strategy and improve the life quality of these patients. METHODS: Clinical materials from January 2008 to December 2010 in 104 adults with ASS-LGG were analyzed retrospectively. The follow-up period ranged from 6 months to 1.5 years. The logistic regression was used to evaluate the preoperative and postoperative variation of functional status in patients to disclose the relevant factors affecting postoperative functional status, such as age, gender, the duration of symptom, size and location of the tumor, hemisphere, resection degree, and tumor pathologic grade and preoperative Karnofsky performance status (Pre-KPS). RESULTS: Four out of nine candidate factors are related to the postoperative functional status. They are age less than 40 years, the size of tumor less than 5 cm in diameter, tumor located in the right hemisphere, and limited resection of tumor in the eloquent area. CONCLUSIONS: It seems more meaningful to evaluate the functional status of the patients with ASS-LGG on the basis of these clinical features, involving age, tumor size, location, and extent of resection.

Reconstructive endovascular treatment of vertebral artery dissecting aneurysms with the Low-profile Visualized Intraluminal Support (LVIS) device.

INTRODUCTION: The Low-profile Visualized Intraluminal Support (LVIS) device is a new generation of self-expanding braided stent recently introduced in China for stent assisted coiling of intracranial aneurysms. The aim of our study is to evaluate the feasibility, safety, and efficacy of the LVIS device in reconstructive treatment of vertebral artery dissecting aneurysms (VADAs). METHODS: We retrospectively reviewed the neurointerventional database of our institution from June 2014 to May 2016. Patients who underwent endovascular treatment of VADAs with LVIS stents were included in this study. Clinical presentation, aneurysmal characteristics, technical feasibility, procedural complications, and angiographic and clinical follow-up results were evaluated. RESULTS: 38 patients with VADAs who underwent treatment with LVIS stent were identified, including 3 ruptured VADAs. All VADAs were successfully treated with reconstructive techniques including the stent-assisted coiling (n = 34) and stenting only (n = 4). Post-procedural complications developed in 3 patients (7.9%) including two small brainstem infarctions and one delayed thromboembolic event. Complications resulted in one case of minor permanent morbidity (2.6%). There was no procedure-related mortality. The follow-up angiogram was available in 30 patients at an average of 8.3 months (range, 2 to 30 months), which revealed complete occlusion in 23 patients (76.7%), residual neck in five patients (16.7%), and residual sac in two patients (6.7%). The follow-up of 25 aneurysms with incomplete immediate occlusion revealed 22 aneurysms (88%) with improvement in the Raymond class. One aneurysm (3.3%) showed recanalization and required retreatment. Clinical followed-up at 5-28 months (mean 14.1 months) was achieved in 36 patients because two patients died of pancreatic cancer and basal ganglia hemorrhage, respectively. No new neurologic deterioration or aneurysm (re)bleeding was observed. CONCLUSIONS: Our preliminary experience with reconstruction of VADAs with the LVIS device demonstrates that this treatment approach is feasible with good short-term angiographic and clinical outcomes. Long-term and larger cohort studies are necessary to determine long-term outcomes of this therapy.

Spinal Arteriovenous Malformation Associated with Parkes Weber Syndrome: Report of Two Cases and Literature Review.

OBJECTIVE: To present 2 cases of Parkes Weber syndrome (PWS) with spinal arteriovenous malformation (AVM) and discuss the radiologic features and clinical treatment with literature review. METHODS: Clinical data on 2 patients with PWS with spinal AVM was acquired in a prospective follow-up investigation. Clinical manifestations, radiographic features, procedural results, and follow-up outcome were collected and reviewed together with a literature review. RESULTS: The first patient presented with limb weakness and urinary dysfunction and the second with repetitive subarachnoid hemorrhage followed by paraplegia. Limb hypertrophy, skin ulceration, and extensive microfistulas in the affected limb were observed in both patients. Spinal AVM was confirmed by digital subtraction angiography and endovascular embolization was performed. The first patient experienced limb amputation at 6-year follow-up as a result of chronic ulceration and the second did not have neurologic improvement. After literature review, 15 cases (male/female ratio, 5:10; mean age, 22±10.4 years) were included. The presentations comprised subarachnoid hemorrhage in 6, radicular pain in 5, myelopathy in 4, and asymptomatic in 1. Embolization was performed in 9 cases, solitary surgery in 2, and combined therapy in 4. Among 10 cases with known follow-up results, 6 achieved neurologic recovery after surgery and 1 died after solitary surgery. CONCLUSIONS: Awareness of the association between spinal AVM and PWS is essential for radiographic screening of spinal lesions with myelopathy or intracranial subarachnoid hemorrhage. Clinical therapeutic strategy should be multidisciplinary and individualized on the basis of vasculature and lesion behavior.