The value of contrast-enhanced three-dimensional isotropic T2-weighted turbo spin-echo SPACE sequence in the diagnosis of patients with lumbosacral nerve root compression.

PURPOSE: To investigate the diagnostic value of contrast-enhanced three-dimensional (3D) T2-weighted turbo spin-echo SPACE (T2-SPACE) sequence in LNRC. METHODS: A total of 90 surgically confirmed LNRC patients with 165 explored nerve roots were enrolled in this study. Diagnostic values were quantified using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. The consistency between 2D MRI and 3D T2-SPACE MRI was quantified using kappa test. The compression of specific branch in nerve root was evaluated on 2D MRI, 3D T2-SPACE MRI, and surgical findings. The pedicle height, vertebral body height (VH), proximal tilting angle of nerve root (PTA) were measured on MR images. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy by 2D MRI were 78.3%, 72.7%, 94.9%, 34.0%, and 77.6%, respectively. For 3D T2-SPACE MRI imaging, the sensitivity, specificity, PPV, NPV, and accuracy were 91.6%, 86.4%, 97.8%, 61.3%, and 90.9%, respectively. 2D MRI and 3D T2-SPACE MRI for detection of intra-foramen and extra-foramen nerve compression showed poor homogeneity (Kappa = 0.333, Kappa = 0.276, respectively). Smaller VHs and larger PTAs could be indicators for the diagnosis of foraminal nerve root compression. CONCLUSIONS: 3D T2-SPACE MRI had a higher sensitivity, specificity, PPV, NPV, and accuracy than 2D MRI for detecting LNRC. The 3D T2-SPACE scan could be a good substitute to routine 2D MRI in LNRC diagnosis, especially for foraminal nerve root compression patients. LEVEL OF EVIDENCE: III.

Correlation between multifidus muscle atrophy, spinopelvic parameters, and severity of deformity in patients with adult degenerative scoliosis: the parallelogram effect of LMA on the diagonal through the apical vertebra.

BACKGROUND: There were several reports describing the biomechanics and microstructure of multifidus muscles in patients with lumbar disc herniation. However, correlations between lumbar multifidus muscle atrophy (LMA), spinopelvic parameters, and severity of adult degenerative scoliosis (ADS) have not been investigated. The study evaluated the impact of LMA and spinopelvic parameters on the severity of ADS. METHODS: One hundred and thirty-two patients with ADS were retrospectively reviewed. Standing whole-spine X-ray was used to evaluate the coronal (coronal Cobb angle, CA; coronal vertical axis, CVA) and sagittal (sagittal vertical axis, SVA; thoracic kyphosis, TK; lumbar lordosis, LL; pelvic incidence, PI; pelvic tilt, PT; sacral slope, SS) parameters. LMA was evaluated on axial T2-weighted magnetic resonance imaging (MRI) at intervertebral levels above and below the vertebra at the apex of the scoliotic curve. Clinical symptoms were evaluated by the Oswestry Disability Index (ODI) and the Japanese Orthopaedic Association (JOA) score. Multiple linear regression was used to assess correlations between LMA, spinopelvic parameters, and severity of scoliosis. RESULTS: LL and PT were negatively correlated with CA (P < 0.001); LL was positively correlated with SVA (P < 0.001). PI was positively correlated with CA (P < 0.001) and CVA (P < 0.001). PT (P < 0.001) and SS (P < 0.001) were negatively correlated with CVA. SS was negatively correlated with SVA (P < 0.001). Concave LMA at the upper or lower intervertebral level of the apical vertebra was positively correlated with CA (P ≤ 0.001); convex LMA at the upper or lower intervertebral level was negatively correlated with CA (P < 0.001). Convex LMA at the upper intervertebral level and concave LMA at the lower intervertebral level of the apical vertebra were negatively correlated with the SVA (P ≤ 0.001). At the upper intervertebral level, LMA on the concave side was positively correlated with CVA (P = 0.028); LMA on the convex side was negatively correlated with CVA (P = 0.012). PI was positively correlated with ODI (P < 0.001); PT (P < 0.001) and SS (P < 0.001) were negatively correlated with ODI. At the lower intervertebral level, LMA on the concave side was positively correlated with ODI (P = 0.038); LMA on the convex side was negatively correlated with ODI (P = 0.011). PI was positively correlated with JOA (P < 0.001); PT (P < 0.001) and SS (P < 0.001) were negatively correlated with JOA. CONCLUSIONS: Spinopelvic parameters are correlated with the severity of ADS. Asymmetric LMA at both upper and lower intervertebral levels of the apical vertebra is positively correlated with CA. LMA on the diagonal through the apical vertebra is very important to maintain sagittal imbalance via parallelogram effect. LMA at lower intervertebral levels of the apical vertebra may have a predictive effect on ODI. JOA score seems to be more correlated with spinopelvic parameters than LMA.

Factors associated with postoperative outcomes in patients with intramedullary Grade II ependymomas: A Systematic review and meta-analysis.

BACKGROUND: Most of the previous studies combined all types of intramedullary ependymomas without providing accurate pathological subtypes. In addition, it was very difficult to evaluate the factors associated with postoperative outcomes of patients with different pathological subtypes of intramedullary Grade II ependymomas by traditional meta-analysis. This study evaluated the factors related with postoperative outcomes of patients with intramedullary Grade II ependymomas. METHODS: Individual patient data analysis was performed using PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published up to April 2018 with no lower date limit on the search results. The topics were intramedullary Grade II ependymomas. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis (log-rank test). The level of significance was set at P < .05. RESULTS: A total of 21 studies with 70 patients were included in this article. PFS of patients who underwent total resection was much longer than the PFS of those who received subtotal resection (P < .001). Patients who received adjuvant therapy (P = .005) or radiotherapy and chemotherapy (P < .001) seemed to have shorter PFS than others; PFS of patients who had cerebrospinal fluid disease dissemination (P = .022) or scoliosis (P = .001) were significantly shorter than others. OS of cellular ependymoma patients was less than giant cell ependymoma patients (P < .001). CONCLUSIONS: PFS of patients who received total resection was much longer than those who received subtotal resection. Patients treated with adjuvant therapy or radiotherapy and chemotherapy appeared to have shorter PFS than others; PFS of patients with cerebrospinal fluid disease dissemination or scoliosis were significantly shorter than others. Cellular ependymomas would have better OS than giant cell ependymoma. However, giant cell ependymoma patients might have the worst OS.

The Parallelogram Effect of Degenerative Structures Around the Apical Vertebra in Patients with Adult Degenerative Scoliosis: The Influence of Asymmetric Degeneration and Diagonal Degeneration on the Severity of Deformity.

BACKGROUND This is the first published study assessing the parallelogram effect of degenerative structures around the apical vertebra. We evaluated the effect of degenerative structures around the apical vertebra and spinopelvic parameters on the severity of ADS. MATERIAL AND METHODS We retrospectively reviewed data on 144 patients with ADS. The coronal (coronal Cobb angle, CA) and sagittal (thoracic kyphosis, TK; sagittal vertical axis, SVA; pelvic incidence, PI; lumbar lordosis, LL; sacral slope, SS; pelvic tilt, PT) parameters, lumbar multifidus muscle atrophy (LMA), and facet joint osteoarthritis (FJOA) were evaluated. Multiple linear regression was used to assess the correlations. RESULTS LL and PT were negatively correlated with CA (P<0.001), and the correlation between LL and SVA was positive (P<0.001), as was the correlation between PI and CA (P<0.001). The correlation between SS and SVA was negative (P<0.001). The correlation between CA and concave LMA at upper or lower intervertebral level of the apical vertebra was positive (P≤0.001). The convex LMA at upper and lower intervertebral levels was negatively correlated with CA (P<0.001). Convex LMA at the upper intervertebral level and concave LMA at the lower intervertebral level of the apical vertebra were negatively correlated with the SVA (P≤0.001). FJOA works similar to LMA (P<0.05). CONCLUSIONS Spinopelvic parameters are correlated with severity of ADS. The structures around the apical vertebra are very important to maintain global alignment of the spine via the parallelogram effect.

Influence of Human Papillomavirus E7 Oncoprotein on Maturation and Function of Plasmacytoid Dendritic Cells In Vitro.

The major difficulties of human papillomavirus (HPV) treatment are its persistence and recurrence. The HPV E7 oncoprotein-loaded dendritic cells have been evaluated as cellular vaccine in previous reports. Plasmacytoid dendritic cells (pDCs) play an essential role of connecting the innate immune response and adaptive immune response in the immune system. But they function in HPV E7 loading is unclear. To investigate whether loading of the HPV type 6b, 11, and 16 E7 proteins affects the activity of pDCs, human peripheral blood-separated pDCs and mouse bone marrow-derived pDCs were pulsed with the HPV E7 proteins. The expression levels of CD40, CD80, CD86, and MHC II were significantly upregulated in pDCs upon HPV 6b/11 E7 protein pulse. The secretion and gene expression of type I IFN and IL-6 were both upregulated by HPV 6b/11 E7 proteins, more significant than HPV 16 E7 protein. The expression of essential factors of TLR signaling pathway and JNK/p38 MAP kinase signaling pathway were all increased in HPV 6b/11 E7 proteins pulsed pDCs. Our results suggest that HPV E7 proteins could promote the differentiation and maturation of pDCs and activate the TLR and MAPK pathway to induce host innate immune response. It might be conducive to explore novel immunotherapy targeting HPV infection with HPV E7 loaded pDC.

Clinical and magnetic resonance imaging predictors of the surgical outcomes of patients with cervical spondylotic myelopathy.

OBJECTIVE: To determine whether clinical characteristics and signal and morphologic changes on magnetic resonance (MR) images of the spinal cord (SC) are associated with surgical outcomes for cervical spondylotic myelopathy (CSM). PATIENTS AND METHODS: A total of 113 consecutive patients with cervical myelopathy underwent cervical decompression surgery in our hospital from January 2015 to January 2018. All patients with preoperative MR images available for review were recruited for this study. Research data included patient sex, age, duration of symptoms, surgical approach, compression level, preoperative mJOA (modified Japanese Orthopaedic Association) score, postoperative mJOA recovery rate, and complications. Imaging data included signal changes on T2-weighted MRI images (grade and extension on sagittal images, four types of signal changes on axial images according to the Ax-CCM system), SC compression, transverse area of the SC, and compression ratio. The t-test, Mann-Whitney U-test, Kruskal-Wallis H - test, analysis of variance, and regression analysis were used to evaluate the effects of individual predictors on surgical outcomes. RESULTS: The study cohort included 85 males and 27 females with a mean age of 60.92 ± 8.93 years. The mean mJOA score improved from 10.24 ± 1.69 preoperatively to 15.11 ± 2.05 at the final follow-up (p < 0.001). Patients in the poor outcome group were more likely to present with a longer duration of symptoms (p < 0.001) and smaller transverse area of the SC (p < 0.001). Bright T2-weighted high signal changes (T2HSCs), multisegmental high signal changes on sagittal MR images, and fuzzy focal T2HSCs on axial MR images were associated with a poor outcome (p < 0.001, p = 0.005, p < 0.001, respectively). The maximum SC compression and compression ratio were not reliable predictors of surgical outcomes (p = 0.375, p = 0.055, respectively). The result of multivariate stepwise logistic regression showed that a longer duration of symptoms, multisegmental T2HSCs on sagittal MR images and fuzzy focal T2HSCs on axial MR images were significant risk factors of poor outcomes (p < 0.001, p = 0.049, p = 0.016, respectively). CONCLUSION: A longer duration of symptom, multisegmental T2HSCs on sagittal MR images, and fuzzy focal T2HSCs on axial MR images were highly predictive of a poor surgical outcome for CSM. Smaller transverse area of the SC and bright T2HSCs were also associated with the prognosis of CSM.

Survival outcomes and prognostic factors of patients with intramedullary Grade II ependymomas after surgical treatments.

This study evaluated survival outcomes of patients with intramedullary Grade II ependymomas and identify prognostic factors. Electronic searches of PubMed, EMBASE, OVID, the Cochrane Central Register of Controlled Trials were performed to identify trials according to the Cochrane Collaboration guidelines. The objects were intramedullary Grade II ependymoma according to 2007 WHO classification. Kaplan-Meier survival analysis with log-rank test was used to analyze progressive free survival (PFS) and overall survival (OS). Cox proportional hazard model was utilized for multivariate analysis with hazard ratio (HR) and 95% confidence interval (CI) calculated. P values <0.05 were considered statistically significant. A total of 28 studies including 138 cases of intramedullary Grade II ependymomas were retrieved. Patients who were classified as cellular ependymomas or papillary ependymomas had higher risks of progression than those who possessed typical Grade II ependymomas. Patients who were treated with adjuvant therapy had a higher risk of progression than those without adjuvant therapy. OS of patients with giant cell ependymoma was significantly shorter than those with typical Grade II ependymoma. Patients who had cellular or papillary subtype, adjuvant therapy would have a shorter estimated value of progression-free time and a higher risk of progression than typical Grade II ependymomas. Giant cell ependymoma patients would have a higher risk of fatality than those with typical Grade II ependymomas. Definite pathology type and appropriate treatments were foundations of intramedullary Grade II ependymomas' managements.

[Establishment of MDCK cell models expressing human MATE1 or co-expressing with human OCT1 or OCT2].

To establish single- and double-transfected transgenic cells stably expressing hMATE1, hMATE1 cDNA was cloned by RT-PCR from human cryopreserved kidney tissue, and subcloned into pcDNA3.1(+) plasmid by virtue of both HindIII and Kpn I restriction enzyme sites. Subsequently, the recombined pcDNA3.1(+)- hMATE1 plasmid was transfected into MDCK, MDCK-hOCT1 or MDCK-hOCT2 cells using Lipofectamine 2000 Reagent. After a 14-day-cultivation with hygromycin B at the concentration of 400 µg · mL(-1), all clones were screened with DAPI and MPP+ as substrates to identify the best candidate. The mRNA content of hMATE1, the cellular accumulation of metformin with or without cimetidine as inhibitor, or transportation of cimetidine was further valuated. The results showed that all of the three cell models over expressed hMATE1 mRNA. The cellular accumulation of metformin in MDCK-hMATE1 was 17.6 folds of the control cell, which was significantly inhibited by 100 µmol · L(-1) cimetidine. The transcellular transport parameter net efflux ratios of cimetidine across MDCK-hOCT1/hMATE1 and MDCK-hOCT2/hMATE1 monolayer were 17.5 and 3.65, respectively. In conclusion, cell models with good hMATE1 function have been established successfully, which can be applied to study the drug transport or drug-drug interaction involving hMATE1 alone or together with hOCT1/2 in vitro.

Stereoselective interaction between tetrahydropalmatine enantiomers and CYP enzymes in human liver microsomes.

Tetrahydropalmatine (THP), with one chiral center, is an alkaloid that possesses analgesic and many other pharmacological actives. The aim of the present study is to investigate stereoselective metabolism of THP enantiomers in human liver microsomes (HLM) and elucidate which cytochrome P450 (CYP) isoforms contribute to the stereoselective metabolism in HLM. Additionally, the inhibitions of THP enantiomers on activity of CYP enzymes are also investigated. The results demonstrated that (+)-THP was preferentially metabolized by HLM. Ketoconazole (inhibitor of CYP3A4/5) inhibited metabolism of (-)-THP or (+)-THP at same degree, whereas the inhibition of fluvoxamine (inhibitor of CYP1A2) on metabolism of (+)-THP was greater than that of (-)-THP; moreover, the metabolic rate of (+)-THP was 5.3-fold of (-)-THP in recombinant human CYP1A2. Meanwhile, THP enantiomers did not show obvious inhibitory effect on the activity of various CYP isoforms (CYP1A2, 2A6, 2C8, 2C9, 2C19, 2E1, and 3A4/5), whereas (-)-THP, but not (+)-THP, significantly inhibited the activity of CYP2D6 with the Ki value of 6.42 ± 0.38 µM. The results suggested that THP enantiomers were predominantly metabolized by CYP3A4/5 and CYP1A2 in HLM, and (+)-THP was preferentially metabolized by CYP1A2, whereas CYP3A4/5 contributed equally to metabolism of (-)-THP or (+)-THP. Besides, the inhibition of CYP2D6 by (-)-THP may cause drug-drug interaction, which should be considered.

Stereoselective metabolism of tetrahydropalmatine enantiomers in rat liver microsomes.

Tetrahydropalmatine (THP), with one chiral center, is an active alkaloid ingredient in Rhizoma Corydalis. The aim of the present paper is to study whether THP enantiomers are metabolized stereoselectively in rat, mouse, dog, and monkey liver microsomes, and then, to elucidate which Cytochrome P450 (CYP) isoforms are predominately responsible for the stereoselective metabolism of THP enantiomers in rat liver microsomes (RLM). The results demonstrated that (+)-THP was preferentially metabolized by liver microsomes from rats, mice, dogs, and monkeys, and the intrinsic clearance (Cl(int)) ratios of (+)-THP to (-)-THP were 2.66, 2.85, 4.24, and 1.67, respectively. Compared with the metabolism in untreated RLM, the metabolism of (-)-THP and (+)-THP was significantly increased in dexamethasone (Dex)-induced and ß-naphthoflavone (ß-NF)-induced RLM; meanwhile, the Cl(int) ratios of (+)-THP to (-)-THP in Dex-induced and ß-NF-induced RLM were 5.74 and 0.81, respectively. Ketoconazole had stronger inhibitory effect on (+)-THP than (-)-THP, whereas fluvoxamine had stronger effect on (-)-THP in untreated and Dex-induced or ß-NF-induced RLM. The results suggested that THP enantiomers were predominately metabolized by CYP3A1/2 and CYP1A2 in RLM, and CYP3A1/2 preferred to metabolize (+)-THP, whereas CYP1A2 preferred (-)-THP.

[Difference absorption of l-tetrahydropalmatine and dl-tetrahydropalmatine in intestine of rats].

To investigate the difference in absorptive of tetrahydropalmatine (THP) and l-tetrahydropalmatine (l-THP) in rat intestine as well as the mechanism of the absorption of THP, in situ single pass perfusion model was used and the concentration of THP in perfusate was determined by HPLC. The absorption rate constant (k(a)) and effective permeability values (P(eff)) of THP had no significant difference (P > 0.05) at concentration of 8, 16 and 32 microg x mL(-1) in perfusion or in four different regions of intestine of rat (duodenum, jejunum, ileum, colon). The absorption of l-THP and THP in jejunum had significant difference (P < 0.05). The k(a) and P(eff) of THP increased obviously when verapamil was co-perfused with THP, while those of l-THP were not influenced by verapamil. The absorption of THP in intestine showed the passive diffusion process, and without a special absorption region. The stereoselective absorption difference may result from stereoselective combination of P-glycoprotein with d-THP.