A network meta-analysis for efficacies and toxicities of different therapeutic regimens in the treatment of advanced nasopharyngeal carcinoma.

PURPOSE: The current study set out to compare the efficacies and toxicities (grad 3 and 4) between concurrent chemoradiotherapy (CCRT), induction chemotherapy plus radiotherapy (IC + RT), IC + CCRT, RT and CCRT + adjuvant chemotherapy (CCRT + AC) in regard to advanced nasopharyngeal carcinoma (NPC) treatment using a network meta-analysis. METHODS: Literature retrieval was conducted using PubMed, Cochrane Library and other English databases. Eligible randomized controlled trails (RCTs) of 5 different regimens were included. The network meta-analysis combined direct and indirect comparisons to measure pooled odd ratios (OR) and the surface under the cumulative ranking curves (SUCRA). RESULTS: A total of eight eligible RCTs were enrolled into this network meta-analysis after initial exclusion. With respect to hematologic toxicity, CCRT + AC exhibited higher toxicity in patients with advanced NPC in terms of anemia and leukopenia/neutropenia compared to RT. As for anemia, the toxicity of IC + CCRT was higher than those with advanced NPC. In addition, CCRT exhibited higher toxicity than RT in relation to leukopenia/neutropenia. Non-hematologic toxicity in regard to nausea/vomiting suggested that CCRT, IC + CCRT and CCRT + AC presented with higher levels of toxicity in patients with advanced NPC, in contrast to RT. Lastly, RT was found to be less toxic but with higher five-year overall survival (OS) rate in patients with advanced NPC, while CCRT, IC + CCRT and CCRT + AC were more toxic in patients with advanced NPC. CONCLUSION: Among the five therapeutic regimens, the survival rate of IC + RT was similar to that of CCRT, and the toxicity SUCRA value of IC + RT was lower than that of CCRT. Together, our findings indicate that IC + RT may be a potentially acceptable treatment alternative to CCRT for advanced NPC, and is worthy of further investigation.

Identification of differentially expressed proteins and validation of the changes of N-ethylmaleimide-sensitive factor in rats with focal cerebral ischemia after transection of the cervical sympathetic trunk.

Stellate ganglion blockade (SGB) protects patients from focal cerebral ischemic injury, and transection of the cervical sympathetic trunk (TCST) in a rat model can mimic SGB in humans. The purpose of this study was to investigate the mechanisms underlying the neuroprotective effects of TCST on neuronal damage in the hippocampus in a rat model of middle cerebral artery occlusion (MCAO) in an attempt to elucidate the neuroprotective effects of SGB. The modified method of Zea Longa was used to establish the permanent MCAO model. Male Wistar rats were randomly divided into three groups: sham-operated group, MCAO group, and TCST group. The animals in TCST group were sacrificed 48 h after TCST which was performed after the establishment of the MCAO model. Proteins were extracted from the ipsilateral hippocampus and analyzed by two-dimensional difference gel electrophoresis (2D-DIGE) and peptide mass fingerprinting (PMF). The levels of N-ethylmaleimide-sensitive factor (NSF) were measured as well. The results showed that 11 types of proteins were identified by 2D-DIGE. The expressions of eight proteins were changed both in the sham-operated and TCST groups, and the expressions of the other three proteins were changed in all three groups. Moreover, the expression of NSF was higher in the TCST group than in the MCAO group but lower in the MCAO group than in sham-operated group. The ratio of NSF expression between the MCAO group and shamoperated group was -1.37 (P<0.05), whereas that between the TCST group and MCAO group was 1.35 (P<0.05). Our results imply that TCST increases the expression of NSF in the hippocampus of adult rats with focal cerebral ischemia, which may contribute to the protection of the injured brain. Our study provides a theoretical basis for the therapeutic application of SGB to patients with permanent cerebral ischemia.

Botulinum Toxin Type A Possibly Affects Cav3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity.

INTRODUCTION: Spinal cord injury (SCI) often causes muscle spasticity, which can be inhibited by using calcium channel blocker. Botulinum toxin type A (BoT-A) shows therapeutic efficacy on spasticity and may exert inhibitory effects on the calcium channel. METHODS: A rat model with muscle spasticity was established after SCI via contusion and compression. Different concentrations (0, 1, 3 and 6 U/kg) of BoT-A Botox were injected in the extensor digitorum longus (EDL) muscles of the right hindlimb in the muscle spasticity model. The changes of muscle spasticity and calcium level in EDL muscles were measured after the establishment of SCI-induced spasticity. Cav3.2 calcium channel subunit and its mutant (M1560V) were analyzed using Western blot before (input) or after immunoprecipitation with anti-FLAG antibody, and their currents were measured in motoneurons by using whole-cell voltage clamp recordings. RESULTS: SCI induced muscle spasticity, whereas calcium level in EDL muscles and expression of Cav3.2 was increased in the SCI model when compared with the sham group (p < 0.05). BoT-A Botox treatment significantly reduced muscle spasticity and calcium level in EDL muscles and Cav3.2 expression in a dose-dependent way (p < 0.05). The ratio of biotinylated to total Cav3.2 was reduced in the mutant (M1560V) of Cav3.2 and lower than that in the wild Cav3.2. BoT-A Botox intervention also reduced the current values of calcium channel and the ratio in a dose-dependent way (p < 0.05). DISCUSSION: BoT-A Botox possibly attenuates SCI-induced muscle spasticity by affecting the expression of Cav3.2 calcium channel subunit in the rat models. There may be multiple mechanisms for the function of BoT-A Botox. Further work is needed to be done to address these issues.

Identification of Biomarkers Related to Neuropathic Pain Induced by Peripheral Nerve Injury.

Our study aimed to explore the molecular mechanisms and novel target genes of neuropathic pain via bioinformatics analysis. Gene expression profiling of GSE30691 which was consisted of sciatic nerve lesion and sham control samples at 3 days, 7 days, 21 days, and 40 days (D3, D7, D21, and D40) after injury were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified for all the four time points. Overlapped DEGs for all the four time points were used for functional and weighted co-expression modular analysis. Afterwards, protein-protein interaction (PPI) network was analyzed by MCODE (Molecular Complex Detection) and BiNGO. Pathway network was constructed according to the enriched pathways of PPI network and relevant pathways selected from the Comparative Toxicogenomics Database. There were 355 overlapped DEGs for all the four time points. Two co-expression modules had significant positive correlations with disease. The top ten hub DEGs in the PPI network were Fos, Tp53, Csk, Map2k2, Stat3, Ccl2, Pxn, Tgfb1, Notch1, and Prkacb. Fos, Dusp1, Tp53, Tgfb1, and Map2k2 participated in MAPK signaling pathway, while Csk participated in chemokine signaling pathway. The expressions of Fos, Tp53, Csk, and Map2k2 were significantly increased at D3. Tp53, Csk, and Map2k2 continued overexpressing until at D7, and an elevated tendency in Csk expression could be observed until at D21. The expression of Fos reached up to the highest at D40. Fos, Tp53, Csk, and Map2k2 might be the potential biomarkers related to neuropathic pain.