[Implement of multimodal navigation-based virtual reality in the needle biopsy of intracranial eloquent lesions].

Objective: To investigate the clinical value of multimodal navigation-based virtual reality (MNVR) in the needle biopsy of intracranial eloquent lesions. Methods: From January 2016 to January 2017, 20 patients with intracranial deep-seated lesions involving eloquent brain areas underwent MNVR-aided needle biopsy at Department of Neurosurgery, People's Liberation Army General Hospital. Preoperatively, MNVR was used to propose and revise the biopsy planning. Intraoperatively, navigation helped trajectory avoid the eloquent structures. Intraoperative MRI (iMRI) was performed to prove the biopsy accuracy and detect the intraoperative complications. Perioperative neurological status, iMRI findings, intraoprative complications, surgical outcome and pathological diagnosis were recorded. Wilcoxon rank-sum test was conducted to compare the preoperative and postoperative neurological scores. Results: MNVR helped revised 45%(9/20) initial biopsy trajectories, which would probably injury the nearby eloquent structures. Navigation helped biopsy trajectories spare the eloquent structures during the operation. No statistical difference was found between postoperative and preoperative neurological status, despite all the lesions were adjacent to eloquent areas. Additionally, 20 patients totally received 21 iMRI scanning. iMRI helped revise incorrect biopsy site in one case and detected intraoperative hemorrhage in another case, both of cases were treated immediately and effectively. No MNVR related adverse events and complications occurred. Conclusions: MNVR-aided needle biopsy of intracranial eloquent lesions is a safe, novel and efficient biopsy modality. This technique is helpful to reduce the incidence of surgery related neurological deficits.

[Implementation of multimodal navigation combined with intraoperative magnetic resonance imaging in the frameless stereotactic biopsy of intracranial lesions].

Objective: To investigate the impact and value of multimodal navigation and intraoperative magnetic resonance imaging (iMRI) on the biopsy of intracranial lesions. Methods: From February, 2009 to December, 2016, this study enrolled 156 patients, who underwent multimodal navigation and iMRI-guided brain biopsy in the Neurosurgery Department of PLA General Hospital. Metabolic information was used for biopsy target selection. Intraoperative guidance helped biopsy trajectory avoid the eloquent structures. iMRI was performed to prove the biopsy accuracy and to revise the incorrect biopsy. Diagnostic rate, perioperative neurological status, surgical parameter, and surgical outcome were recorded. Results: The first iMRI helped to revise 7 (4.5%) incorrect biopsy sites, and final iMRI confirmed biopsy accuracy in all cases. Postoperative diagnostic rate was 96.8% (151/156). No statistical difference was found between postoperative and preoperative neurological statuses, despite 86 (55.1%) lesions were adjacent to eloquent areas. Additionally, iMRI detected 6 (3.8%) intraoperative hematomas that were treated immediately. Conclusions: Brian biopsy with iMRI and multimodal navigation is a safe, accurate and efficient biopsy modality. This technique may help increase the biopsy accuracy with low morbidity and mortality.

[Treatment of single one-stage posterior atlantoaxial fixation in Chiari malformation].

Objective: To explore the effects of surgical technique of single one-stage posterior C(1-2) screw rod fixation of Chiari malformation (CM) associated with occipitalization and without atlantoaxial dislocation. Methods: A total of 23 patients with CM treated between January 2014 and October 2015 in Department of Neurosurgery of Chinese People's Liberation Army General Hospital were retrospective reviewed. All of them were diagnosis with CM associated with occipitalization and without atlantoaxial dislocation, including 8 males and 15 females, aging from 11 to 57 years (mean (35.5±10.52) years). Single one-stage posterior C(1-2) screw rod fixation with bone grafting fusion was performed. Operation time and intraoperative blood loss were recorded. Japanese Orthopaedic Association (JOA) scores and Odom rating were used to evaluate the clinical effects at pre- and post-operative. Regression of the cerebellar tonsillar was measured by MRI. The results were analyzed by paired samples t test. Results: Twenty-three patients were implanted screws successfully, the vertebral artery injury and cerebrospinal fluid leakage were not found. The mean operation time was (172.7±19.9) minutes, the intraoperative blood loss was (153.9±49.3) ml. Compared to preoperative, the JOA score increased (13.7±1.6 vs. 11.5±1.4) and the tonsillar herniation decreased ((0.8±0.6)cm vs. (1.9±0.6) cm) in the last follow-up, there were statistical difference (t=13.386, P<0.01; t=17.995, P<0.01). The results of the postoperative Odom grading were as follows: 6 cases were perfect (26.1%), 13 cases were good (56.5%), 4 cases were moderate (17.4%) and no case was poor.No signs of instrument loosen or screw broken was noticed. 100% bony fusion rate was achieved. The follow-up time was 6 to 23 months (mean (10.5±3.2) months). One case developed internal fixator related discomfort, the symptom was relieved by internal fixator removal surgery performed 4 months after the operation when osseous fusion had already been achieved. No new neurologic symptoms were observed in other 22 patients. Conclusions: The results of the study substantiates the effectiveness of single one-stage posterior fixation strategy for CM, which is associated with occipitalization and without atlantoaxial dislocation. This technique could be an alternative choice for this type of CM.

[Clinical useness of multimodal techniques in microsurgical resection of cerebral arteriovenous malformation].

Objective: To explore the clinical useness of intraoperative functional neuronavigation and fluorescent indocyanine green(ICG) angiography as well as electrophysiological evaluation during microsurgical resection of cerebral arteriovenous malformations (AVM). Methods: A series of 42 consecutive cases with AVM underwent microsurgery by intraoperative functional neuronavigation at Department of Neurosurgery of People's Liberation Army General Hospital from January 2009 to February 2015 were retrospectively analyzed. Of the 42 patients, 29 were males and 13 were females aging from 4 to 62 years (mean age 32.6 years). Preoperative assessment included functional magnetic resonance imaging and diffusion tensor imaging to identify the relationship between lesions and eloquent areas. The results of images were integrated into three-dimensional datasets to achieve intraoperative microscopic-based functional neuronavigation during AVM resection. Operations involved in motor areas and corticospinal tract were performed under continuous electrophysiological monitoring. ICG angiography was performed at pre-dissection, post-clipping of the feeders, and post-resection of the nidus. FLOW 800 software presented a color map and ICG intensity-time curve to demostrate the vascular architecture. Postoperative digital subtraction angiography was re-examined routinely to evaluate the extent of resection. Clinical outcomes were evaluated with the modified Rankin Scale. Results: All patients underwent surgery under intraoperative navigation. Of the 42 patients, total resection was achieved in 36 cases (85.7%, 36/42) including 14 cases of AVM in eloquent areas. A total of 40 ICG angiographies were successfully performed among 11 patients. Average number of ICG injections per operation was 3.6 (ranging from 3 to 6). Feeders were visualized in 10 patients and drainers were visualized in 9 cases. The post-surgical follow-up period varied from 3 months to 70 months (mean 22.5 months). 83.8% of the patients returned to normal work and life during the followed-up period. Conclusion: Combining intraoperative neuronavigation and electrophysiological monitoring, as well as fluorescent ICG angiography contribute to microsurgical resection of cerebral AVM effectively in selecting suitable patients, further avoiding neurologic compromise as well.

[Copy number variants analysis in whole-genome of patients with lipoma tethered cord syndrome].

Objective: To explore the abnormality of chromosomes of patients with lipoma tethered cord syndrome and the probable association between Copy Number Variations (CNV) and lipoma tethered cord syndrome. Methods: By using the Agilent SurePrint G3 Human CGH 8×60K Microarray Kit, we performed genome-wide screening for CNV on 11 patients with lipoma tethered cord syndrome adopted by the Neurosurgery Department of Chinese PLA General Hospital and their healthy parents from March 2015 to May 2015. We analyze CNVs got by the kit against the gene databases. Unrelated confirmed polymorphisms contained in Database of Genomic Variants (DGV) were discarded. Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER) helps us with similarity inquiry, and UCSC Genome Browser helps in identification of non-polymorphic CNV. Biological process, cellular component and molecular function enrichment of these genes were conducted to confirm the association between the CNV and lipoma tethered cord syndrome. Results: 17 CNV were discovered by aCGH in 11 patients. Chr8: 39258894-39386158 and Chr15: 20481702-22509254 showed a high frequency of 5/11. Angelman syndrome and Prader-Wolli syndrome were found to be associated with the CNV of Chr15. Gene function enrichment analysis revealed that ADAM5P and ADAM3A contained in CNV obtained from patients with lipoma tethered cord syndrome was also associated with orofacial clefts. Conclusions: CNV in Chr8 and Chr15 of patients with lipoma tethered cord syndrome had a higher frequency than that of common human. It revealed that there is probable association between these two pieces of CNV and lipoma tethered cord syndrome. To explorer related genes or CNV, focusing on certain type of NTDs may increase the research efficiency and get more accurate results.

Pharmacokinetic of four probe drugs in adriamycin-induced nephropathy rat.

BACKGROUND AND AIM: Probe drugs have been widely used to assess the activities of various CYP450 (cytochromes P450) isoenzymes in many fields of drug metabolism and pharmacogenetics. The nephrotic syndrome characterized by massive proteinuria and hypoproteinemia, whether that would influence the pharmacokinetics of probe drugs or not is still unclear. The purpose of the study was to investigate the pharmacokinetic of four probe drugs in adriamycin (ADR)-induced nephropathy rat. MATERIALS AND METHODS: The rats were randomly divided into Control-group (n = 10) and ADR-group (n = 10). Nephrotic syndrome was established by weekly injections of ADR for 2 weeks. After dynamic monitoring of 24-h total urinary protein for 4 weeks, we confirmed that nephrotic syndrome had developed. The rats were administered intragastrically with phenacetin, tolbutamide, omeprazole and bupropion (15, 5, 15, and 15 mg/kg, respectively). The blood samples were determined by LC-MS (Liquid Chromatography-Mass Spectrometry) method. RESULTS: The pharmacokinetics parameter of tolbutamide in ADR-group and Control-group were AUC(0-t) 15.371 ± 4.107, 6.901 ± 5.738 (mg/L*h), MRT(0-t) 8.751 ± 0.754, 6.032 ± 0.63 (h), t1/2 3.88 ± 0.423, 3.602 ± 0.693 (h), Tmax 6.2 ± 3.768, 1.95 ± 0.798 (h), CL/F 0.038 ± 0.005, 0.107 ± 0.037 (L/h/kg), V/F 0.212 ± 0.043, 0.567 ± 0.258 (L/kg), Cmax 1.853 ± 0.384, 1.422 ± 1.312 (mg/L). There was statistical difference in AUC, MRT, CL, V and Tmax of tolbutamide between two groups (p < 0.05), but no pharmacokinetics difference for phenacetin, bupropion and omeprazole. CONCLUSIONS: The pharmacokinetics of tolbutamide was changed in ADR-induced nephropathy rat. It is not suitable for tolbutamide to evaluate the activity of CYP450 in nephrotic syndrome.

Increasing hepatitis B viral load is associated with risk of significant liver fibrosis in HBeAg-negative but not HBeAg-positive chronic hepatitis B.

BACKGROUND/AIMS: To evaluate the association between demographical features, serum ALT and HBV DNA and the prevalence of significant fibrosis and inflammation on liver biopsy in patients with chronic hepatitis B. METHODS: In this cross-sectional study of patients on St Vincent's Hospital HBV database, patients were classified into three groups on the basis of HBeAg status and HBV DNA level and the prevalence of significant (F2/3/4) fibrosis and (A2/3) inflammation in each group was established. Patients were also divided into HBeAg-positive and -negative groups and examined for the prevalence of significant fibrosis/inflammation in the strata of HBV DNA and ALT. Predictors of significant fibrosis and inflammation in HBeAg-positive and -negative patients were examined by logistic regression. RESULTS: Three hundred and ninety four patients (HBeAg positive=198; HBeAg negative=196) with liver biopsy were identified. Fifty-eight percent of HBeAg-negative patients with HBV DNA >25,000 IU/ml had F2/3/4 fibrosis. HBV DNA and F2/3/4 were positively correlated in HBeAg-negative patients [odds ratio (OR) 1.42, P=0.001] but inversely correlated in HBeAg-positive patients (OR 0.71, P=0.03). HBV DNA was an independent predictor of significant fibrosis in HBeAg negative (P=0.03) but not HBeAg-positive patients. In HBeAg-positive patients, age was the only predictor of significant fibrosis (P=0.001) and ALT the only predictor of significant inflammation (P=0.003). In the whole cohort there was a close positive association between inflammation and fibrosis. CONCLUSION: Increasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis only in patients with HBeAg-negative CHB.

Low molecular mass polypeptide-2 in human trophoblast: over-expression in hydatidiform moles and possible role in trophoblast cell invasion.

Embryo implantation involves invasion of placental extravillous trophoblast cell (EVTs) into the uterus. Hyperactive EVT invasion occurs in hydatidiform moles and choriocarcinomas. We have previously demonstrated that the 20S proteasome is involved in mouse embryo implantation and its action is mediated via regulating the expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 in the EVTs. Our objective was to investigate whether low molecular mass polypeptide-2 (LMP2), a beta subunit of the 20S proteasome, is involved in the regulation of human trophoblast invasion. Normal human placentas or placentas from hydatidiform mole patients were collected and the expression of LMP2 in different cell types including trophoblastic column (TC), cytotrophoblast cells (CTB) and syncytiotrophoblast (STB) under different pathological states were studied by immunohistochemical analysis. Furthermore, the effect of LMP2 or proteasome on cell invasion was measured by using RNAi and inhibitors in a Matrigel invasion assay system in HTR-8/SVneo cells, a human invasive extravillous trophoblast cell line. Changes in the invasion-related molecules including MMP-2 and MMP-9 were also examined by using real time PCR and gelatin zymography. We demonstrated that the expression of LMP2 in TC of partial hydatidiform mole and complete hydatidiform mole, is higher than that in TC of normal human placentas. Besides, LMP2 knockdown significantly attenuated IL-1beta-induced cell invasion in vitro, a response readily induced by proteasome inhibitors. In summary, over-expression of the 20S proteasome beta-subunit LMP2 in trophoblast cells of hydatidiform moles may contribute to its highly invasive phenotype.