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Neuropathic pain is a very complex chronic pain state, the detailed molecular mechanisms of which remain unclear. In the present study, Shank3 was found to play an important role in neuropathic pain in rats following spared nerve injury (SNI). Shank3 was upregulated in the spinal dorsal horn of rats subjected to SNI, and mechanical hypersensitivity to noxious stimuli in these rats could be alleviated by knock down of Shank3. Shank3 also interacted with hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and promoted the expression of HCN2 in central neurons of the spinal dorsal. Together with the SNI-dependent increase of HCN2, we also found that the postsynaptic protein of excitatory synapse (PSD95) was increased in rats following SNI. Taken together, our results showed that Shank3 modulated neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95 in spinal dorsal horn neurons. Our findings revealed new synaptic remodeling mechanisms linking Shank3 with neuropathic pain.

Background This study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian®) plus cisplatin (SP regimen) and 5‐fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA‐NPC). Methods Eligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco‐regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity. Results In this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow‐up period, the estimated 3‐year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3‐year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3‐4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05). Conclusions These data indicate that SP and FP therapies have similar efficacy in treating LA‐NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA‐NPC treatment., The incidence of other adverse effects seen in both groups was similar (P > .05).The efficacy of both regimens i.e. SP and FP are found similar. The SP regimen has tolerable safety profile, with a lower incidence of severe OM and consequently, an improved quality of life.

ObjectiveTo investigate whether perioperative ultrasound-guided serratus anterior plane block (SAPB) combined with general anesthesia is more effective and safer than current analgesic techniques for postoperative analgesia after video-assisted thoracoscopic surgery (VATS).MethodsPubMed, the Cochrane Library, and EMBASE were searched for clinical trials published up to July 31, 2019. Outcomes, including operative duration, postoperative pain scores, postoperative analgesia use, patient satisfaction with analgesia, time to chest tube removal, length of stay, and adverse effects were analyzed.ResultsFour clinical trials, including 262 patients, met inclusion criteria. Ultrasound-guided SAPB reduced pain scores at zero, 15, 30, 45, and 60 minutes in the postoperative anesthesia care unit (all P 0.05).ConclusionsPerioperative ultrasound-guided SAPB combined with general anesthesia provided more effective postoperative analgesia after VATS. However, no significant advantage was found regarding side effects.

Background Recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis have opened a new field of utilizing circulating miRNAs as cancer biomarkers. In this pilot study, we conducted for the first time, to our knowledge, the evaluation of the applicability of salivary miRNAs as novel biomarkers for nasopharyngeal carcinoma (NPC) detection. Methods Microarray miRNA expression profiling was performed on saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls, and 12 significantly down-regulated miRNAs were selected for quantitative real-time-PCR (qRT-PCR) validation and further analysis. Their target genes enriched by gene ontology and pathway analysis were used to construct regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy. Results Twelve dysregulated miRNAs screened by microarray that showed the same expression patterns with qRT-PCR analysis. Through bioinformatics analysis, the most prominent hub gene probably regulated by the 12 down-regulated miRNAs is found to be TP53. The ROC including the 12 miRNAs separated NPC patients from healthy controls with very high accuracy (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%). Furthermore, if only six significantly dysregulated miRNAs were selected for the ROC analysis, the accuracy is still impressive (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%). Conclusions This study highlights the potential for salivary miRNAs as biomarkers for the detection of NPC. Meanwhile, differentially expressed miRNAs in saliva might play critical roles in NPC by regulating their target genes, which associated with some significant pathways, such as p53 signaling pathway. Electronic supplementary material The online version of this article (10.1186/s12885-019-6037-y) contains supplementary material, which is available to authorized users.

Background: This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods: A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results: After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

Lung cancer is the most common solid tumor around the world. It has been reported that upregulation of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (lncRNA-PVT1) is closely associated with tumor metastasis. However, the function and underlying molecular mechanism of lncRNA-PVT1 in nonsmall cell lung cancer (NSCLC) invasion remain unknown. In this study, we found that overexpression of lncRNA-PVT1 promoted the invasive ability of NSCLC cells, whereas silence of lncRNA-PVT1 suppressed cell invasion. Furthermore, we found that lncRNA-PVT1 upregulated MMP9 expression in a post-transcriptional manner. Specifically, lncRNA-PVT1 directly interacted with miR-200a and miR-200b, which suppressed MMP9 expression. Taken together, lncRNA-PVT1 functions as a competitive endogenous RNA to regulate MMP9 expression through competitively binding the common microRNAs, miR-200a and miR-200b. These findings suggest that lncRNA-PVT1 could predispose NSCLC patients to metastases and may serve as a promising target for antimetastatic therapies.

Neuronal network reconstruction is a pivotal determinant for functional recovery after spinal cord injury (SCI), the process of which includes synaptogenesis. Slit2 protein has been identified as a key regulator of axon regeneration and synapse formation in the vertebrate. Meanwhile, RhoA is the converging cascade of inhibitory molecules that interrupt synaptic plasticity in SCI. In the present study, we investigated the interaction among Slit2, Robo1, and RhoA and the potential roles of Slit2 in the pathological process of SCI. We showed that Slit2 was decreased, whereas Robo1 and RhoA were increased in the same surviving neurons in the spinal cord following SCI. We also found that inhibition of Slit2 led to upregulation of the expression of Robo1 and RhoA. However, the severe dysfunctions of the locomotor performance induced by SCI were reversed by treatments of Slit2-N, the active portion of Slit2, knockdown of Robo1 by the RNAi lentivirus, or inhibition of RhoA by the C3 exoenzyme, respectively. Further results suggested that downregulation of Slit2 and therefore upregulation of Robo1 and RhoA inhibited the activity of growth cone and hindered the formation of new synapses of surviving neurons near the injury sites of the spinal cord following SCI. Our study indicated a new mechanism of deficiency of synaptogenesis during the development of SCI and provided a potential strategy for the treatment of SCI.

Table S1. The dysregulated (down-regulated) miRNAs in the NPC samples with the cutoff criteria of P 2. Table S2. Putative target genes of the dysregulated miRNAs in the saliva samples of NPC patients. Table S3. The enriched Gene Ontology (GO) terms in molecular function (MF), biological process (BP) and cellular component (CC) categories for target genes of all the 12 differentially expressed miRNAs. FDR: false discovery rate. Table S4. The top ten enriched pathways for target genes of all the 12 differentially expressed miRNAs. Table S5. The target genes with degrees not less than five in the protein-protein interaction network. Table S6. Sequences of RT primer, and PCR primers used for quantitative real-time PCR (qRT-PCR). Table S7. Detail information of protein-protein interactions from the Search Tool for the Retrieval of interacting Genes database (STRING) online. Figure S1. Validation of the miRNA expression (miR-937-5p, miR-650, miR-3612, miR-4478, miR-4259, miR-3714, miR-4730, miR-1203, miR-30b-3p, miR-1321, miR-1202, and miR-575) by qRT-PCR in 22 patients and 25 healthy controls. Figure S2. ROC curves of the diagnostic potential of the 12 individual salivary miRNAs (has-miR-30b-3p, has-miR-575, has-miR-650, has-miR-937-5p, has-miR-1202, has-miR-1203, has-miR-1321, has-miR-3612, has-miR-3714, has-miR-4259, has-miR-4478, and has-miR-4730) in discrimination between NPC patients and healthy controls. The AUC values ranged from 0.764 to 0.883, respectively. Figure S3. Diagnostic miRNA expressions were classified into 3 different patterns based on various clinical stages. (DOCX 1214 kb)

// Jie Luo 1, * , Xiaoxia Huang 2, * , Yali Li 1 , Yang Li 1 , Xueqin Xu 1 , Yan Gao 1 , Ruoshi Shi 1 , Wanjun Yao 1 , Juying Liu 1 , Changbin Ke 1 1 Institute of Anesthesiology & Pain (IAP), PET-CT, Institute of Anesthesiology and Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan City, 442000, Hubei Province, China 2 Department of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan City, 442000, Hubei Province, China * These authors have contributed equally to this work Correspondence to: Changbin Ke, email: Changbinke@gmail.com Keywords: bone cancer pain, spinal cord, GPR30, excitatory transmission, inhibitory transmission Received: June 13, 2016 Accepted: August 26, 2016 Published: September 06, 2016 ABSTRACT Cancer induced bone pain is a very complicated clinical pain states that has proven difficult to be treated effectively due to poorly understand of underlying mechanism, but bone cancer pain (BCP) seems to be enhanced by a state of spinal sensitization. In the present study, we showed that carcinoma tibia implantation induced notable pain sensitization and up-regulation of G-protein-coupled estrogen receptor (GPR30) in the spinal cord of rats which was reversed by GPR30 knockdown. Further studies indicated that upregulation of GPR30 induced by cancer implantation resulted in a select loss of γ-aminobutyric acid-ergic (GABAergic) neurons and functionally diminished the inhibitory transmission due to reduce expression of the vesicular GABA transporter (VGAT). GPR30 contributed to spinal cord disinhibition by diminishing the inhibitory transmission via upregulation of α1 subunit and downregulation of γ2 subunits. GPR30 also facilitated excitatory transmission by promoting functional up-regulation of the calcium/calmodulin-dependent protein kinase II α (CaMKII α) in glutamatergic neurons and increasing the clustering of the glutamate receptor subunit 1 (GluR1) subunit to excitatory synapse. Taken together, GPR30 contributed to the development of BCP by both facilitating excitatory transmission and inhibiting inhibitory transmission in the spinal cord. Our findings provide the new spinal disinhibition and sensitivity mechanisms underlying the development of bone cancer pain.

The results implied that CTCs were common even in early TNM stages and might become a potential parameter in evaluating therapeutic effects of radio and chemotherapies.Nasopharyngeal carcinoma (NPC) is a head and neck malignancy with an extraordinary high incidence in Southern China and a high metastasis rate. Analysis of circulating tumor cells (CTCs) in peripheral blood is a relatively new prognostic marker for cancer patients.This retrospective study included data from 38 nasopharyngeal patients with poorly differentiated squamous cell carcinoma in TNM stage I (n = 2), TNM stage II (n = 12), TNM stage III (n = 8), and TNM stage IV (n = 16). CTCs in peripheral blood of all patients were counted before and 1 week as well as 1 months after radiotherapy.The data showed that in 52.6% of the patients CTCs could be detected in peripheral blood and the numbers were significantly decreased 1 month after radiotherapy treatment (p 0.001). There was no correlation between CTC number or positivity and TNM stages or other clinical parameters.

Mobile Internet has changed the way of information acquisition and dissemination, which also brings new challenges to the teaching of Higher Vocational colleges. Teachers must keep up with the development of technology. By understanding the new needs of College students, teachers can reform the teaching content, teaching methods, teaching design and so on. Through the teaching reform, vocational colleges can cultivate comprehensive applied talents adapted to the mobile internet. This paper first analyses the significance of higher vocational education reform under the background of mobile internet. Then, this paper analyses the problems existing in the teaching of Higher Vocational Colleges in the era of mobile internet. Finally, some suggestions are put forward.

MicroRNA-98 (miR-98) is downregulated in many tumors, and is closely related to tumor progression. In addition, it shows anticarcinogenic functions in various tumor. However, few study show that the biological function and regulatory mechanisms of miR-98 in nasopharyngeal carcinoma (NPC) progression. The identification and its target genes which regulate by dysregulated miRNAs may strengthen our understanding of the molecular mechanisms of NPC. In this study, we observe that miR-98 is not only significantly reduced in NPC tissues, but also decreased markedly in NPC cell lines. Moreover, silencing miR-98 expression studies not only show miR-98 induced cell proliferation, migration and invasion in vitro, but also it promoted xenograft tumor growth in vivo in NPC. Furthermore, western blot assay was used to detected the level of STAT3 protein and we demonstrate that miR-98 regulate cells poliferation, migration and invasion through directly modulating functional target STAT3 by directly binding its 3'-UTR. These findings illustrate miR-98 as a anticarcinogenic functions through targeting STAT3, the miR-98/STAT3 pathway gives new clues for understanding NPC carcinogenesis and provides novel therapeutic targetsfor NPC.

Bone cancer pain (BCP) is a serious chronic clinical condition and reactive oxygen species (ROS) were considered to be involved in its development and persistency. Normally, superoxide dismutase (SOD) converts superoxide anions to hydrogen peroxide (H2O2) and H2O2 is then naturalized to be water by peroxiredoxin 4. We reported previously that recombinant protein transduction domain (PTD)-Cu/Zn SOD effectively scavenged excessive ROS and prevented cardiomyocytes from hypoxia–reoxygenation damage. However, whether PTD-Cu/Zn SOD would prevent BCP development is unknown. In the current study, we found that an implanted carcinoma in the rat tibia induced remarkable hyperalgesia, increased H2O2 levels and decreased SOD and peroxiredoxin 4 levels. After administration of recombinant PTD-Cu/Zn SOD to these tumor-burden rats, their hyperalgesia was significantly attenuated and peroxiredoxin 4 expression was significantly increased. In addition, an increased expression of N-methyl-d-aspartic acid (NMDA) receptors and a decreased expression of γ-aminobutyric acid (GABA) receptors in this cancer pain were prevented by PTD-Cu/Zn SOD administration or peroxiredoxin 4 overexpression. Our data suggested that reactive oxygen species, at least in part, play a role in cancer metastatic pain development and persistency which can be attenuated by the adminstration of recombinant PTD-Cu/Zn SOD via the peroxiredoxin 4 modulation from oxidative stress.

Intensity-modulated radiotherapy (IMRT) has been applied in nasopharyngeal carcinoma (NPC) for nearly twenty years, while little is known about the ten-year survival outcomes. This study aimed at evaluating the 10-year survival outcomes for patients with NPC receiving IMRT.Data on 614 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2004 and 2008 were retrospectively reviewed. Survival outcomes stratified by tumor stage were compared.The median follow-up duration was 112.7months (range, 7.6-156.8months) for the entire cohort. The 10-year local relapse-free survival rates for T1, T2 and T3 were 94.2%, 92.5% and 91.4% (P0.05), respectively, and significantly higher than that of T4 disease (79.3%, P0.05 for all rates). As N category increased from N0 to N3, the 10-year distant metastasis-free survival rates significantly decreased accordingly (P0.01 for all rates). Furthermore, the 10-year overall survival rates were 100%, 87.1%, 75.5% and 55.6% for stage I, II, III and IV, respectively (P0.05 except stage I and II). Multivariate analysis established tumor stage and age as independent prognostic factors. Late toxicities were assessable for 495 (80.6%) patients and most were Grade I/II damages. Xerostomia (387 of 489, 79.1%) and hearing impairment (212 of 495, 42.8%) remained the most troublesome.IMRT could achieve satisfactory survival outcomes for NPC patients with acceptable late toxicities. However, distant control still remains poor, especially for patients with N3 disease.

Bone cancer pain is refractory to currently available clinical treatment owing to its complicated underlying mechanisms. Studies found that extracellular matrix molecules can participate in the regulation of chronic pain. Decorin is one of the most abundant extracellular matrix molecules, and the present study evaluated the effect of decorin on the development of bone cancer pain. We found that decorin was upregulated in the L4–L6 spinal dorsal horn of the bone cancer pain rats. Spinal microinjection of a decorin-targeting RNAi lentivirus alleviated bone cancer pain-induced mechanical allodynia and reduced the expression of pGluR1-Ser831 in the bone cancer pain rats. Meanwhile, decorin knockdown impaired the excitatory synaptogenesis in cultured neurons and prevented the clustering and insertion of pGluR1-Ser831 into postsynaptic membranes. Taken together, the results of our study suggested that decorin contributes to the development of bone cancer pain possibly by regulating the activity of excitatory synaptic molecules in the spinal cord. Our findings provide a better understanding of the function of decorin as a possible therapeutic target for alleviating bone cancer pain.

Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with functional impairment. Prolonged hypothermic storage–induced ischemia-reperfusion injury is associated with the early onset of CAN. As the noble gas xenon is clinically used as an anesthetic and has renoprotective properties in a rodent model of ischemia-reperfusion injury, we studied whether early treatment with xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1α individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model, xenon exposure of donors before graft retrieval or recipients after engraftment enhanced tubular cell proliferation and decreased tubular cell death and cell inflammation associated with ischemia-reperfusion injury. Compared with control allografts, xenon treatment significantly suppressed T-cell infiltration and fibrosis, prevented the development of CAN, and improved renal function. Thus, xenon treatment promoted recovery from ischemia-reperfusion injury and reduced susceptibility to the subsequent development of CAN in allografts.

Although beta-catenin cytoplasmic stabilization and nuclear translocation play a key role in initiation of colorectal cancer (CRC), the mechanisms are far from clear. The aim of this study was to investigate the relation of expressions of cyclooxygenase (COX)-2 and E-cadherin, and the beta-catenin gene exon 3 mutation to the altered distribution of beta-catenin, and their roles in CRC progression and prognosis.Expressions of beta-catenin, COX-2 and E-cadherin in 96 tissue specimens were detected by immunohistochemistry, and mutation of beta-catenin gene exon 3 was screened by polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC).Cytoplasmic/nuclear expression of beta-catenin and reduced membranous expression of E-cadherin were associated, respectively, with the earlier and later stages of sequential colorectal carcinogenesis (p0.05). The altered distribution of beta-catenin was significantly associated with both high Dukes' stages and poor differentiation of CRC (p0.05). It also had a parallel relationship with COX-2 overexpression (p0.05, Spearman's rank analysis), but not with reduced E-cadherin expression. Kaplan-Meier analysis showed a significantly worse survival rate for CRC patients with altered expression of beta-catenin (p0.05, log-rank test). Nevertheless, we failed to find any exon 3 mutation of beta-catenin gene in all 60 cases of CRC.Altered distribution of beta-catenin occurs in the early stage of colorectal carcinogenesis and has a parallel relationship with COX-2 overexpression. It may serve as a potential marker for the progression and prognosis of CRC. The exon 3 mutation did not appear contributive to the abnormal expression of beta-catenin in CRCs in a Chinese population.