Valproate reverses stress-induced somatic hyperalgesia and visceral hypersensitivity by up-regulating spinal 5-HT2C receptor expression in female rats.

Sodium valproate (VPA) has analgesic effects in clinical and experimental studies, but the mechanisms are still unclear. The present study examined the effects of VPA on stress-induced somatic hyperalgesia and visceral hypersensitivity and the role of 5-HT2C receptors in the spinal cord. Repeated 3 day forced swim (FS) significantly reduced the thermal withdrawal latency and mechanical withdrawal threshold, and increased the magnitude of the visceromotor response to colorectal distention compared to the baseline values in rats. The somatic hyperalgesia and visceral hypersensitivity were accompanied by significant down-regulation of 5-HT2C receptor expression in the L4-L5 and L6-S1 dorsal spinal cord. Intraperitoneal administration of VPA (300 mg/kg) before each FS and 1 day post FS prevented the development of somatic hyperalgesia and visceral hypersensitivity induced by FS stress, as well as down-regulation of 5-HT2C receptors in the spinal cord. The reversal of somatic hyperalgesia and visceral hypersensitivity by VPA in FS rats was blocked by intrathecal administration of the selective 5-HT2C receptor antagonist RS-102221 (30 µg/10 µL) 30 min after each VPA injection. The results suggest that VPA attenuates FS-induced somatic hyperalgesia and visceral hypersensitivity by restoring down-regulated function of 5-HT2C receptors in the spinal cord.

Low-Level Laser Therapy for Temporomandibular Disorders: A Systematic Review with Meta-Analysis.

Objectives: We systematically reviewed randomized controlled trials (RCTs) of the effect of low-level laser therapy (LLLT) versus placebo in patients with temporomandibular disorder (TMD). Methods: A systematic search of multiple online sources electronic databases was undertaken. The methodological quality of each included study was assessed using the modified Jadad scale, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Results: A total of 31 RCTs were included. Total modified Jadad scale scores showed that the methodological quality was high in 30 studies and low in 1 study. Combining data from all clinically heterogeneous studies revealed positive effects of LLLT on pain relief, regardless of the visual analogue scale (VAS) score or the change of VAS score between the baseline and the final follow-up time point, while dosage analyses showed discrepant results about the effects of high or low doses for patients with TMD. Follow-up analyses showed that LLLT significantly reduced pain at the short-term follow-up. Temporomandibular joint function outcomes indicated that the overall effect favored LLLT over placebo. Conclusion: This systematic review suggests that LLLT effectively relieves pain and improves functional outcomes in patients with TMD.

Burr-Hole Craniostomy with T-Tube Drainage as Surgical Treatment for Chronic Subdural Hematoma.

OBJECTIVE: We sought to investigate the effect of burr-hole craniostomy with T-tube drainage to treat chronic subdural hematoma (CSDH). METHODS: Eighty-seven patients with CSDH who were recruited from January 2012 to June 2017 at the Department of Neurosurgery, The First Affiliated Hospital of Xi'an Medical University, were divided into 2 groups according to the method of drainage: T-tube drainage system (n = 45) and conventional subdural drainage system (n = 42). Retrospective analysis of clinical data and efficacy was performed between the 2 groups. RESULTS: There were no significant differences in age, preoperative Markwalder grade scale, preoperative hematoma volume, hospitalization days, and discharge Markwalder grade scale between the 2 groups (P > 0.05). The incidence of postoperative complications and hematoma recurrence in the group of patients with T-tube drainage was significantly reduced when compared with conventional subdural drainage systems (P < 0.05). CONCLUSIONS: Both methods were effective in the treatment of CSDH; however, we found a lower overall surgical complication rate following treatment with burr-hole craniostomy and T-tube drainage. This indicates that it may be a better therapeutic option for management of CSDH.

Complementary and alternative interventions for fatigue management after traumatic brain injury: a systematic review.

BACKGROUND: We systematically reviewed randomized controlled trials (RCTs) of complementary and alternative interventions for fatigue after traumatic brain injury (TBI). METHODS: We searched multiple online sources including ClinicalTrials.gov, the Cochrane Library database, MEDLINE, CINAHL, Embase, the Web of Science, AMED, PsychINFO, Toxline, ProQuest Digital Dissertations, PEDro, PsycBite, and the World Health Organization (WHO) trial registry, in addition to hand searching of grey literature. The methodological quality of each included study was assessed using the Jadad scale, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. A descriptive review was performed. RESULTS: Ten RCTs of interventions for post-TBI fatigue (PTBIF) that included 10 types of complementary and alternative interventions were assessed in our study. There were four types of physical interventions including aquatic physical activity, fitness-center-based exercise, Tai Chi, and aerobic training. The three types of cognitive and behavioral interventions (CBIs) were cognitive behavioral therapy (CBT), mindfulness-based stress reduction (MBSR), and computerized working-memory training. The Flexyx Neurotherapy System (FNS) and cranial electrotherapy were the two types of biofeedback therapy, and finally, one type of light therapy was included. Although the four types of intervention included aquatic physical activity, MBSR, computerized working-memory training and blue-light therapy showed unequivocally effective results, the quality of evidence was low/very low according to the GRADE system. CONCLUSIONS: The present systematic review of existing RCTs suggests that aquatic physical activity, MBSR, computerized working-memory training, and blue-light therapy may be beneficial treatments for PTBIF. Due to the many flaws and limitations in these studies, further controlled trials using these interventions for PTBIF are necessary.

Erlotinib for advanced hepatocellular carcinoma. A systematic review of phase II/III clinical trials.

OBJECTIVES: To evaluate the efficacy and safety of erlotinib for the treatment of advanced hepatocellular carcinoma (HCC). METHODS: A systematic literature search was undertaken in June 2015. Phase II/III trials of erlotinib for the treatment of advanced HCC were included. A descriptive analysis was applied. The study was conducted in College of Medicine, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China, between June 2015 and January 2016. RESULTS: Ten trials, comprising 9 phase II and one phase III trial, were included in the systematic review. The tumor response rate was 0% in 4 of the phase II trials, less than 10% in 3 of the phase II trials and the phase III trial, and greater than 20% in 2 of the phase II trials. The disease control rate was 42.5-79.6% in most studies. Three studies reported a median progression-free survival (PFS) of 6.5-9.0 months, although PFS was less than 3.5 months in most studies. Most trials reported a median overall survival of 6.25-15.65 months. The most frequent grade 3/4 toxicities were fatigue (11.9%), diarrhea (10%), increased alanine and aspartate transaminases (7.3%), and rash/desquamation (6.9%). Conclusion: Erlotinib provides efficacious and well-tolerated treatment for advanced HCC. However, more detailed investigations of HCC pathogenesis and evaluation of sensitive patient subsets are needed to improve outcomes of patients with advanced HCC. Additional well-designed, randomized, controlled trials are needed to evaluate the efficacy and safety of erlotinib as monotherapy or combination with other drugs for advanced HCC.

MicroRNA-130b promotes cell migration and invasion by targeting peroxisome proliferator-activated receptor gamma in human glioma.

MircroRNA-130b (miR-130b) has been recognized as an oncogenic miRNA and is implicated in the initiation and development of human cancers. Deregulation of miR-130b has been reported in several tumors. However, the clinical significance and its underlying role in human glioma are poorly explored. Herein, we found that the expression of miR-130b was significantly up-regulated in glioma tissues as compared with that in normal brain (NB) tissues. Clinical association analysis disclosed that high-expression of miR-130b was evidently associated with advanced tumor stage (grade III+IV) in glioma. Moreover, we disclosed that the high-expression of miR-130b conferred an obviously reduced survival of glioma patients. Multivariate Cox regression analysis showed that miR-130b expression was an independent prognostic indicator for glioma patients. Our gain- or loss-of-function studies showed that miR-130b promoted invasion and migration of glioma cells. Notably, miR-130b regulated peroxisome proliferator-activated receptor gamma (PPARγ) abundance and epithelial-mesenchymal transition (EMT) in glioma cells. Hereby, PPARγ was identified as a functional target of miR-130b in glioma. Furthermore, an inverse correlation between miR-130b and PPARγ expression was observed in glioma tissues. In conclusion, miR-130b is an independent prognostic biomarker for indicating survival of glioma patients and promotes glioma cell migration and invasion by targeting PPARγ.

A Systematic Review of Adjuvant Interventions for Radioiodine in Patients with Thyroid Cancer.

AIMS: The purpose of this study was to assess the effects of adjuvant interventions for radioiodine in patients with thyroid cancer. MATERIALS AND METHODS: A systematic search was undertaken on July 9, 2014. RevMan 5 software was used to synthesize data. RESULTS: 13 randomized controlled trials were included. The pooled risk ratio of 0.99 (95% confidence interval (CI): 0.96-1.02, p = 0.58) indicated no significant difference in successful thyroid remnant ablation between recombinant human thyroid-stimulating hormone (rhTSH) and thyroid hormone withdrawal in 7 trials. The percentage of patients who had successful ablation was significantly higher in the oral-lithium group than in the control group (p = 0.017). A computerized decision aid improves informed decision-making in patients with early-stage papillary thyroid cancer (PTC) who are considering adjuvant radioiodine treatment (p < 0.001). Amifostine pretreatment did not prevent parenchymal damage to the major salivary gland function after radioiodine treatment (p = 0.2461). CONCLUSIONS: The present systematic review suggests that rhTSH, lithium, and computerized decision aids maybe act as beneficial adjuvant interventions for radioiodine in patients with thyroid cancer; however, amifostine does not exhibit helpful effects in thyroid cancer patients treated with radioiodine.

Magnesium sulfate for acute traumatic brain injury.

BACKGROUND: The purpose of this systematic review was to evaluate the effect of magnesium sulfate in the treatment of acute traumatic brain injury. MATERIALS AND METHODS: A systematic search of ClinicalTrials.gov, the Cochrane Library database, EMBASE, MEDLINE, Web of Science, and the World Health Organization trial registry, plus manual searches of gray literature, was undertaken in April 2013. Two reviewers independently extracted the data with a predefined data extraction form. RevMan 5 software was used to synthesize data and calculate the risk ratio for mortality with the 95% confidence interval. For the Glasgow Outcome Scale and posttreatment Glasgow Coma Scale data, the weighted mean difference was calculated with the 95% confidence interval. RESULTS: A total of 8 randomized controlled trials with a total of 786 patients were included. Meta-analysis showed that there was no significant difference between the groups for mortality. The Glasgow Outcome Scale of the treatment group was higher than that of the control group, although the significance was borderline. The Glasgow Coma Scale score change posttreatment was significantly higher than that of the control. CONCLUSIONS: The present meta-analysis of existing randomized controlled trials does not identify a significant beneficial effect in the mortality of traumatic brain injury patients; however, it suggests that magnesium sulfate shows a tendency to improve the Glasgow Outcome Scale and Glasgow Coma Scale scores, which is a promising result for traumatic brain injury therapy. Further effort is necessary to explore which subgroup of traumatic brain injury patients could benefit from magnesium sulfate.

Fibulin-5 is a prognostic marker that contributes to proliferation and invasion of human glioma cells.

Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studies have shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. This study was aimed to investigate the clinical significance of fibulin-5 in glioma and its role in cell proliferation and invasion. We found that the expression of fibulin-5 in glioma tissues was significantly lower than those in normal brain (NB) tissues. Negative expression was significantly correlated with advanced clinical stage (grade III+IV). Furthermore, Fibulin-5 negative expression was correlated with a shorter overall survival of glioma patients. Multivariate Cox repression analysis indicated that fibulin-5 was an independent factor for predicting overall survival of glioma patients. Overexpression obviously inhibited cell proliferation in U251 and U87 cells. Furthermore, it significantly reduced the number of migrating and invading glioma cells. In conclusion, impaired expression of fibulin-5 is correlated with the advanced tumor stage in glioma. Otherwise, Fibulin-5 is an independent prognostic marker for predicting overall survival of glioma patients. Mechanistically, it may function as a tumor suppressor via inhibiting cell proliferation and invasion in gliomas.

[Silencing of carcinoembryonic antigen-related cell adhesion molecule 1 inhibits proliferation and induces apoptosis in human glioma SHG44 cells].

OBJECTIVE: To investigate the effect of siRNA-induced silencing of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) on proliferation and apoptosis in human glioma SHG44 cells. METHODS: Three pairs of specific siRNA targeting CEACAM1 were designed and synthesized, and then transiently transfected into SHG44 cells via cationic liposome transfection method. Transfection efficiency was examined by flow cytometry (FCM). Real-time quantitative PCR (qRT-PCR) and Western blotting were respectively used to detect CEACAM1 expression at mRNA and protein levels, and the proliferation ability and apoptosis of SHG44 cells after transfection were assessed by CCK-8 assay and FCM in combination with annexin V-FITC/PI staining, respectively. The expression levels of cleaved caspase-3 and cleaved poly(ADP-ribose)polymerase (PARP) proteins were detected by Western blotting. RESULTS: The efficiency of CEACAM1 siRNA transfection into human SHG44 cells were 85%. Forty-eight hours after the three pairs of specific CEACAM1 siRNA were transfected into SHG44 cells, qRT-PCR and Western blot results showed that the expression of CEACAM1 mRNA and protein were significantly inhibited compared with those in the blank control and the negative control groups, and the most significant interference effect was CEACAM1-siRNA3. The proliferation of SHG44 cells was inhibited and the apoptosis rate was raised by the CEACAM1-siRNA transfection. The expression levels of cleaved caspase-3 and cleaved PARP proteins were up-regulated after silencing of CEACAM1. CONCLUSION: The siRNA-mediated CEACAM1 silencing can inhibit the proliferation and promote the apoptosis in human glioma SHG44 cells. CEACAM1 gene may be used as a potential therapeutic target of glioma.

Early pressure dressing for the prevention of subdural effusion secondary to decompressive craniectomy in patients with severe traumatic brain injury.

This study was performed to investigate the effect of early pressure dressing on the prevention of postoperative subdural effusion secondary to decompressive craniectomy (DC) in patients with severe traumatic brain injury (STBI). Patients with STBI who had undergone DC for refractory increased intracranial pressure between January 2008 and December 2011 (n = 169) were randomly divided into early pressure dressing (n = 82) and control (n = 87) groups. Early pressure dressing with an elastic bandage or general wrapping (control treatment) was applied 7 to 10 days after DC. Patients' age, sex, preoperative Glasgow Coma Scale score, incidence rate of subdural effusion, hospitalization time, and postoperative Glasgow Outcome Scale score were compared between groups. Intracranial pressure was measured immediately before and on the day after pressure dressing. No significant difference in age, sex, preoperative Glasgow Coma Scale score, or postoperative Glasgow Outcome Scale score was observed between groups (P > 0.05). Subdural effusion incidence rates were significantly lower in the early pressure dressing group than those in the control group (χ² = 5.449, P = 0.021), and a larger proportion of patients in the early pressure dressing group was hospitalized for 30 days or less (χ² = 5.245, P = 0.027). Early pressure dressing 7 to 10 days after DC, which is a noninvasive, simple procedure, reduced the incidence rate of subdural effusion and shortened hospitalization time after DC for STBI.

A rare remote epidural hematoma secondary to decompressive craniectomy.

Remote epidural hematoma (REDH) is an uncommon complication of decompressive craniectomy. Remote epidural hematomas of the parietal occiput region have been reported only rarely. We report a unique case of delayed-onset bilateral extensive straddle postsagittal sinus and bilateral lateral sinus parietal occiput REDH after decompressive craniectomy, of which volume was approximately 130 mL, with left deviating midline structures. The patient was immediately taken back to the operating room for evacuation of the REDH via bilateral parietal and occiput craniectomy. Postoperatively, serial computed tomographic scans performed 3 days later showed that the REDH had been completely evacuated. Two months later, the patient regained full consciousness and obtained a near-complete recovery except for right facial paralysis.

A meta-analysis of treating acute traumatic brain injury with calcium channel blockers.

The purpose of this systematic review was to evaluate and meta-analyse the current evidence for the use of calcium channel blockers (CCBs) in the treatment of acute traumatic brain injury (TBI) and traumatic subarachnoid haemorrhage (tSAH). A systematic search of clinical trials.gov, Cochrane library databases, EMBASE, MEDLINE, Web of science search and WHO trial registry, plus hand-searching of grey literature, was undertaken in March 2013. Two reviewers independently extracted the data using a pre-defined data extraction form. RevMan 5 software was used to synthesise data and calculate the risk ratio (RR) based on event rates as well as the 95% confidence interval (CI). Finally, nine RCTs with a total of 2182 patients were included. Meta-analysis showed that there was no difference between CCBs and control groups for rates of mortality (n=1337, 5 RCTs, RR 0.93 CI 0.77-1.12). In a subgroup tSAH analysis, the difference was not significant (n=389, 2 RCTs, RR 0.73 CI 0.53-1.02). There were slightly fewer unfavourable outcomes in the treatment group, but the difference was not statistically significant (n=2101, 8 RCTs, RR 0.90 CI 0.76-1.08). In the subgroup tSAH analysis, again, the difference did not reach statistical significance (n=1074, 5 RCTs, RR 0.95 CI 0.73-1.24). It seems that larger, well-designed RCTs are necessary in order to ascertain any clinical benefit CCBs may or may not have for the treatment of acute TBI.

[Expression and significance of CEACAM1 and HBx in HBV related hepatocellular carcinoma].

AIM: To investigate the expression and clinical significance of CEACAM1 and HBx in HBV related hepatocellular carcinoma. METHODS: The expression of CEACAM1 and HBx in 81 HBV related hepatocellular carcinoma were detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. The expression of CEACAM1 in the human normal hepatocyte cell line QZG, HepG2 and HepG2-X were detected by Western blot. RESULTS: The positive rate of CEACAM1 and HBx in 81 HBV related hepatocellular carcinoma tissues were 71.60%(58/81) and 74.07%(60/81) respectively. The expression of CEACAM1 and HBx were correlated with portal vein invasion, nodal metastasis and TNM staging. The expression of CEACAM1 was negative correlated with HBx(r(s);=-0.310, P<0.01). CEACAM1 protein was significantly down regulated in HepG2-X than in HepG2-PC and human normal hepatocyte cell line QZG. CONCLUSION: The higher expression of HBx and lower expression of CEACAM1 are correlated with invasion and metastasis of HBV related hepatocelular carcinoma, CEACAM1 may be a effect molecule in HBV related hepatocarcinogenesis.