Identification and clinical validation of gene signatures with grade and survival in head and neck carcinomas.

This study aimed to explore gene expression profiles that drive malignancy from low- to high-grade head and neck carcinomas (HNC), as well as to analyze their correlations with survival. Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low- and high-grade HNC were screened. Cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). The genes were experimentally validated by RT-PCR in clinical tissue specimens. Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Cox regression analyses showed that CXCL14, SLC44A1, and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients were grouped into high-risk or low-risk groups for prognosis based on gene signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033 and P=0.010, respectively). Multivariate Cox regression showed HPV (P=0.033), lymph node status (P=0.032), and residual status (P<0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858 and AUC=0.901, respectively). The results showed CXCL14 and SLC44A1 were significantly overexpressed in the low-grade HNC tissues and the UBD were overexpressed in the high-grade HNC tissues. Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarkers to predict survival.

Identification and clinical validation of gene signatures with grade and survival in head and neck carcinomas

This study aimed to explore gene expression profiles that drive malignancy from low- to high-grade head and neck carcinomas (HNC), as well as to analyze their correlations with survival. Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low- and high-grade HNC were screened. Cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). The genes were experimentally validated by RT-PCR in clinical tissue specimens. Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Cox regression analyses showed that CXCL14, SLC44A1, and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients were grouped into high-risk or low-risk groups for prognosis based on gene signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033 and P=0.010, respectively). Multivariate Cox regression showed HPV (P=0.033), lymph node status (P=0.032), and residual status (P<0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858 and AUC=0.901, respectively). The results showed CXCL14 and SLC44A1 were significantly overexpressed in the low-grade HNC tissues and the UBD were overexpressed in the high-grade HNC tissues. Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarkers to predict survival.

1H NMR-based nontargeted metabonomics study of plasma and urinary biochemical changes in Kudouzi treated rats

Abstract Kudouzi (Sophora alopecuroides L., Fabaceae) is an effective folk medicine, but it always causes a hepatic and renal toxicity in clinical therapy. The toxic mechanism remains unclear. This paper detected the urinary and plasma metabolites alteration by 1H NMR-based metabonomics study in Kudouzi-induced rats to evaluate the toxic mechanism for clinical security. The male Sprague-Dawley rats were orally dosed with 0.5 and 1 g Kudouzi/kg weight once per day for consecutive 14 days. Urine samples were collected at day −1 (before treatment), and days 7, 14, and 21 for NMR analysis, respectively. Plasma samples were harvested at day 14 for NMR and biochemical analysis. The metabonomic profiling of Kudouzi-treated rats differed from that of the vehicle. This was confirmed by the biochemistry analysis. The accumulated subacute toxicity of Kudouzi was visible with dosing time, and persisted at day 21 even after the disposal was ended. The observable biochemical pathways alterations included inhibited TCA cycle, activated anaerobic glycolysis, perturbed amino acids metabolism, and disordered gut microbiota. The results evidenced the toxicity mechanism of Kudouzi from a systematic and holistic view.

Different processing methods change the oral toxicity induced by Sophora alopecuroides seeds and the contents of five main toxic alkaloids from the ethanol extracts determined by a validated UHPLC-MS/MS assay

Abstract This study investigated the influence of different processing methods on the oral toxicity of Sophora alopecuroides L., Fabaceae, seeds in mice and on the contents of five known toxic-effective quinolizidine alkaloids from the ethanol extracts quantified by ultra-performance liquid chromatography coupled to tandem quadrupole mass spectrometry. It provides an evidence to elucidate the possible reasons why vinegar-processing and parching methods significantly decrease the acute oral toxicity induced by S. alopecuroides and why wine-processing method increases it instead (demonstrated by measurement of LD50 and histopathological analysis). The analytical performance for the determination of the five analytes was evaluated by linearity, stability, repeatability, precision and accuracy, and recovery test. The lowest limit of quantification was determined to be 5 ng/ml for each substance and the precision and accuracy at lowest limit of quantification were below 20%. Cytisine, the most toxic alkaloid among the five alkaloids, declined 11.26, 3.98, and 2.73 folds after being vinegar-processed and fried in a ceramic or iron pan, respectively and had a very close correlation with the toxicity of S. alopecuroides seeds (r = 0.8589). Other matrine-type alkaloids with lower toxicity including matrine, sophcarpine, and sophoridine decreased after being wine-processed and fried in a ceramic pan, but increased 4.44, 7.20, and 7.23 folds when being processed by vinegar. Oxymatrine declined in all groups. It, therefore, reveals that vinegar-processing method reduces the oral toxicity of S. alopecuroides mainly due to a sharp decrease of cytisine, thus improves its clinical safety.

Impact of chrysosplenetin, per se or in combination with artemisinin, on breast cancer resistance protein (Bcrp)/ABCG2 mRNA expression levels in mice small intestine

ABSTRACT Our previous work revealed that chrysosplenetin in combination with artemisinin inhibited in vivo P-glycoprotein (P-gp, one of classic multi-drug resistance proteins) mediated digoxin transportation activity by reversing the upregulated P-gp/Mdr1 mRNA expression levels by artemisinin. Therefore, chrysosplenetin might be a potential artemisinin-resistance reversal agent as a P-gp inhibitor. But it still remains unknown if chrysosplenetin has an impact on another pivotal multi-drug resistance protein, breast cancer resistance protein (Bcrp), which is co-expressed with P-gp in apical membrane of intestinal epithelial cell and overlaps some of the substrates and inhibitors. This study, therefore, further addressed the impact of chrysosplenetin, per se or in combination with artemisin, on Bcrp/ABCG2 mRNA expression levels in mice small intestine determined by western blot and real time-quantitative polymerase chain reaction (RT-qPCR) assay. The drugs were intragastrically administrated once per day for 7 days. Novobiocin, a known Bcrp inhibitor, was observed to have no impact on Bcrp/ABCG2 levels with or without artemisinin versus vehicle. Interestingly, artemisinin alone attenuated Bcrp level while chrysosplenetin alone increased it (p < 0.05). Relative mRNA level was significantly decreased when co-used with artemisinin and chrysosplenetin in ratio of 1:2 (p < 0.05). The discrepant results for chrysosplenetin on Bcrp/ABCG2 mRNA expressions might be closely related to the transcriptional or posttranscriptional regulation.

Conservative and Operative Treatment in Extension Teardrop Fractures of the Axis.

STUDY DESIGN: A retrospective case series describing teardrop fracture of the axis. OBJECT: The purpose of the study was to clarify the clinical features, the mechanism of injury, and the potential instability of extension teardrop fractures of the axis, so as to emphasize the importance of recognizing this injury as a separate entity. SUMMARY OF BACKGROUND DATA: Teardrop fractures of the axis are rare spinal fractures, comprising only a small percentage of all injuries of the cervical spine. The stability of this fracture pattern has been a matter of debate leading to controversy regarding treatment strategies and the need for stabilization. METHODS: We retrospectively reviewed data collected from 16 patients to document the mechanism of injury, neurological deficit, treatment and clinical outcome, and imaging findings. RESULTS: Extension teardrop fractures accounted for approximately 8.9% of the upper cervical spinal injuries and 12.7% of axis fractures at the authors' institution over the same period. Six patients (4 males and 2 females) underwent surgery (4 by an anterior approach, 2 by a posterior approach). Ten cases underwent Halo-vest immobilization for a period between 6 and 12 weeks. At final follow-up, 14 cases achieved excellent results, whereas 2 patients complained of mild residual neck pain. Maximum cranial-caudal dimensions of the fragments were between 5 and 24 mm (average, 12.9 mm), and the transverse dimensions were between 5 and 22 mm (average, 11.1 mm). Fragment displacement ranged from 1 to 9 mm (average, 3.5 mm), whereas fragment rotation ranged from 10 to 52 degrees (average, 24.4 degrees) in the sagittal plane. CONCLUSIONS: Most patients with an extension teardrop fracture of the axis can be treated conservatively. On the basis of this case series, the authors suggest that large fragment size, displacement or angulation, intervertebral disk injury, neurologic deficit, or signs of instability are reasonable indications for surgical treatment.

Function-preserving reduction and fixation of unstable Jefferson fractures using a C1 posterior limited construct.

STUDY DESIGN: This is a retrospective, clinical, and radiologic study of posterior reduction and fusion of the C1 arch in the treatment of unstable Jefferson fractures. OBJECTIVE: The aim of the study was to describe a new motion-preserving surgical technique in the treatment of unstable Jefferson fracture. SUMMARY OF BACKGROUND DATA: The management of unstable Jefferson fractures remains controversial. The majority of C1 fractures can be effectively treated nonoperatively with external immobilization unless there is an injury to the transverse atlantal ligament (TAL). Conservative treatment usually involves immobilization for a long time in Halo vest, whereas surgical intervention generally involves C1-C2 fusion, eliminating the range of motion of the upper cervical spine. We propose a novel method for the treatment of unstable Jefferson fractures without restricting the range of motion. METHODS: A retrospective review of 12 patients with unstable C1 fractures between April 2008 and October 2011 was performed. They were treated by inserting bilateral posterior C1 pedicle screws or lateral mass screws interconnected by a transversal rod to achieve internal fixation. There were 8 men and 4 women, with an average age of 35.6 years (range, 20-60 y). Presenting symptoms included neck pain, stiffness, and decreased range of motion but none had neurological injury. Seven patients had bilateral posterior arch fractures associated with unilateral anterior arch fractures (posterior 3/4 Jefferson fracture, Landells type II), and 5 had unilateral anterior and posterior arch fractures (half-ring Jefferson fracture, Landells type II). Seven patients had intact TAL, and 5 patients had fractures and avulsion of the attachment of TAL (Dickman type II). RESULTS: A total of 24 screws were inserted. Five cases had screws placed in the lateral mass: 3 because of posterior arch breakage, and 2 because the height of the posterior arch at the entry point was <4 mm. The remaining 7 cases had pedicle screw fixation. One patient had venous plexus injury during exposure of lower margin of the posterior arch; however, successful hemostasis was achieved with Gelfoam. Postoperative x-ray and computed tomography scan showed partial breach of the transverse foramen caused by a screw in 1 case, and breach of the inner cortex of the pedicle caused by screw displacement in 1 case; however, no spinal cord injury or vertebral artery injury was found. The remaining screws were in good position. Patients were followed up for 6-40 months (average, 22 mo). All cases had recovery of range of motion of the cervical spine to the preinjury level by 3-6 months after surgery, with resolution of pain. At 6 months follow-up, plain radiographs and computed tomography scans revealed satisfactory cervical alignment, no implant failure, and satisfactory bony fusion of the fractures; no C1-C2 instability was observed on the flexion-extension radiographs. CONCLUSIONS: C1 posterior limited construct is a valid technique and a feasible method for treating unstable Jefferson fractures, which allows preservation of the function of the craniocervical junction, without significant morbidity.