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PURPOSE This randomized controlled phase II study investigated the efficacy, safety and underlying mechanism of maxillofacial and oral massage (MOM) in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy. METHODS A total of 158 NPC patients were randomly assigned 1:1 to routine oral care and medication (the control group) or that with additional MOM (the treatment group). The primary endpoint was the incidence of severe radiotherapy-induced oral mucositis (SRTOM). In addition, the time of initiation and duration of RTOM and SRTOM, adverse events, dynamic changes of lipid metabolites in peripheral blood were analyzed. RESULTS Seventy-six patients in the treatment group and seventy-nine in the control group completed the trial. The incidence of SRTOM in the treatment group was lower than the control (26.3% vs. 46.8%, P = 0.008). The median initiation time to RTOM and SRTOM was significantly longer in the treatment group than the control (RTOM:12 vs 10 days, hazard ratio [HR] 0.52, P

In order to solve the problem of difficult gas extraction in coal mine, a method of gas extraction from coal seam by interval hydraulic flushing is put forward. Based on the coal seam gas occurrence conditions of 7609 working face in Wuyang Coal Mine, the numerical simulation research on gas drainage by ordinary drilling and hydraulic flushing drilling was carried out by using COMSOL numerical simulation software. The results show that with the increase of hydraulic flushing coal quantity, the effective gas drainage radius also increases. The effective extraction radius of ordinary drilling is 0.5 m, and the effective extraction radius is 1.0 m, 1.2 m and 1.3 m respectively when the coal flushing quantity is 0.5t/m, 1.0t/m and 1.5t/m. As multiple boreholes are drained at the same time, the boreholes will affect each other, which will reduce the gas pressure and increase the effective drainage radius, the spacing between boreholes can be greater than twice the effective drainage radius of a single borehole when arranging boreholes. And the smaller the flushing interval, the more uniform the gas pressure reduction area. According to the numerical simulation results, the ordinary drilling and 1.0t/m interval hydraulic flushing test were carried out in the field. Through observation and analysis, the gas concentration of the interval hydraulic flushing drilling module was increased by 31.2% and the drainage purity was increased by 5.77 times compared with the ordinary drilling module. It shows that the interval hydraulic flushing drilling can effectively improve the gas drainage effect.

A Gram-positive, aerobic, non-spore-forming, non-pigmented and non-motile actinobacterial strain was isolated from a soil sample collected in Guangzhou, China. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain 130T is most closely related to the type strain Nocardioides iriomotensis NBRC 105384T, with a sequence similarity of 97.69 %. The isolate was distinguished from this phylogenetically related type strain by DNA–DNA hybridization (33.3 %), digital DNA–DNA hybridization (21.2 %), average nucleotide identity (75.7 %) and by a range of physiological and biochemical characteristics. Strain 130T contained MK-8(H4) and MK-7 as the major menaquinones, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol as the main polar lipids, and iso-C16 : 0, C17 : 1ω8c, anteiso-C17 : 0, C18 : 1ω9c, C17 : 0 and iso-C14 : 0 as the major cellular fatty acids. The novel strain grew at 20–36 °C, at pH 6.0–8.0 and in the presence of 0–6 % (w/v) NaCl. The genomic DNA G+C content was 72.9 mol%. The genome contained 4817 putative protein-coding sequences, and 45 tRNA and three rRNA genes. Phylogenomic analysis confirmed that strain 130T belongs to the genus Nocardioides and distinguished it from recognized Nocardioides species with available genomes. Based on these polyphasic taxonomic data, strain 130T represents a new species of the genus Nocardioides , for which the name Nocardioides guangzhouensis sp. nov. is proposed. The type strain is 130T (=CICC 24668T=JCM 33269T).

Purpose The direction and orientation of the osteotomized upper segments in dental implant distractor (DID) can be compromised due to an unpredicted vector of distraction. The present study aimed to evaluate the accuracy of computer-aided design/computer-aided manufacturing (CAD/CAM) surgical templates to precisely guide the distraction process in lengthening of the alveolar height for functional mandibular reconstruction. Patients and methods This retrospective study included all consecutive patients who underwent digitally designed mandibular reconstruction using the fibular flap and DID with the help of CAD/CAM designed surgical templates in a single-stage procedure from 2011 to 2014. First, the preoperative digital planning was performed on 3-dimensional models. Afterward, simulation of the distraction process was made on the virtual model and the resulting new height of the fibula was evaluated. The preoperative simulation was applied to accurately define the exact location and path of the DID device to achieve the suitable vertical height. The preoperative digital planning was used to help the design of the CAD/CAM surgical template, which was then fabricated by means of the 3-dimensional printing technology. The manufactured surgical template-assisted both horizontal and vertical osteotomies of the fibular segments and defining the DID path to lead the distractor into the accurate position. The outcome evaluation was achieved through comparing both preoperative virtual planning with postoperative actual outcomes. Results This study included 14 subjects, 8 were males and 6 were females. The mean age at time of surgery was 31.07 years (range 18-47). All fibular flaps showed 100% success rate. The mean vertical bone height attained with the DID device was 11.35 mm. The vertical and horizontal osteotomies of the fibular segments were completed, then the DID devices were successfully positioned guided by the template. The mean values of the linear and angular deviations for the distractor position and upper segments were calculated and recorded. The maximum linear deviation between the virtual and the postoperative actual distractors was 0.93 mm in the anteroposterior direction, and the greatest in the horizontal plane was 4.64°. Conclusions CAD/CAM surgical templates can accurately guide the direction and orientation of the DID device for functional mandibular reconstruction; therefore, helping to improve the outcomes by accurately transferring the preoperative virtual plan to real surgical procedure.

Background: Epstein–Barr virus (EBV) infection contributes to cancers in a fraction of seropositive individuals, but much remains to be learned about variation in EBV-directed humoral immunity in cancer-free adults. Methods: A protein microarray was used to probe serum from 175 Taiwanese and 141 Northern European adults for immunoglobulin G (IgG) antibody responses to 115 different peptide sequences, representing protein segments or protein variants, from 45 EBV proteins. It was posited that this antibody-based approach could identify EBV peptide sequences representing immunodominant regions relevant for B-cell immunity. Results: Analyses of 45 EBV proteins with multiple protein segments or variants printed on the array identified eight EBV peptide sequences that appear to play a role in immunogenicity. This included: (1) three proteins with segments/regions associated with IgG reactivity (BALF5, LMP1, LMP2A); and (2) five proteins with sequence variants/amino acid changes associated with IgG reactivity (BDLF4, EBNA3A, EBNA3B, EBNA-LP, LF1). Conclusion: This examination of IgG antibody responses against 115 EBV peptide sequences in 316 cancer-free adults represents an important step toward identifying specific EBV protein sequences that play a role in generating B-cell immunity in humans.

Objective This meta-analysis was conducted to investigate the relationship between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis (RA) susceptibility. Methods Eligible studies were retrieved from PubMed, Embase, and Web of Science. The fixed- or random-effects model was used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) on the basis of heterogeneity. Results Overall, 11 studies containing 4019 RA patients and 4137 controls were included in this meta-analysis. The results suggested a significant association between the IL-17A rs2275913 polymorphism and RA susceptibility in the overall population (allelic model A vs. G: OR = 0.89, 95%CI: 0.83–0.95; heterozygote model GA vs. GG: OR = 0.87, 95%CI: 0.78–0.96; homozygote model AA vs. GG: OR = 0.82, 95%CI: 0.71–0.96; dominant model GA + AA vs. GG: OR = 0.86, 95%CI: 0.78–0.94). In the subgroup analyses, the IL-17A rs2275913 polymorphism was significantly associated with RA risk in Europeans (allelic model A vs. G: OR = 0.87, 95%CI: 0.78–0.97; heterozygote model GA vs. GG: OR = 0.79, 95%CI: 0.68–0.93; dominant model GA + AA vs. GG: OR = 0.79, 95%CI: 0.68–0.92), but not in Africans or Americans. Conclusion This study suggests that the IL-17A rs2275913 polymorphism is significantly associated with RA susceptibility in Europeans. INPLASY registration number: INPLASY202170056.

With the rapid development of new energy vehicle industry, the recycling of automotive traction battery has become the focus of resource sustainable development. In order to build the whole life cycle digital management system, this paper innovatively designs data management system of the traceability of the traction battery, achieving the efficient management of traction battery life cycle data and providing data support for industrial policy research.

Pharyngocutaneous fistula (PCF) is one of the most common but stranded complications for salvage laryngectomy. As for localized fistula, there is no convincing standard and method to cure. This paper described a patient who was submitted to extensive resection of mass in right lingual root, total laryngectomy, and pharyngoesophageal reconstruction with an anterolateral thigh flap (ALTF), because of recurred carcinoma of right lingual root which invaded bilateral epiglottis. 2 weeks after surgery, subsequent pharyngocutaneous fistula developed at the junction of the tracheostomy, and maintained over 2 months under conservative treatment. With the assistance of laryngoscope, inner and outer orificiums of fistula were found and sealed by bundled iodoform strip. 9 days after sealing, fistula had been already filled with fresh granulation tissue. During 2 years after surgery, the fistula area dose not recur. This technique provides a safe and effective way for sealing the inner and outer orificiums of fistula.

Background We aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC). Methods A total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort). Results Using the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort. Conclusion AE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.

Objective: To explore the pharmacodynamic mechanism of Fu Zi Li Zhong Decoction (FZLZD) in treating gastric ulcer and its effect on gastrointestinal microecology. Methods: Rat gastric ulcer model was established by continuous vinegar gavage. The experiment included normal group, model group, ranitidine group and FZLZD group. The animals were handled after intragastricing administration of corresponding clinical isodose drugs for 7 d. The rats’ gastrointestinal histopathology was observed by HE staining. The expression of ZO-1 and Occludin mRNA in rat gastric tissue was detected by RT-PCR. The diversity of intestinal flora was analyzed by 16SrDNA sequencing. Results: FZLZD can effectively improve gastric mucosal destruction, epithelial exfoliation, inflammatory cell infiltration, inflammatory substance exudation and edema in rats with gastric ulcer. FZLZD can effectively up-regulate the expression levels of ZO-1 and Occludin mRNA in gastric tissue of rats with gastric ulcer. The results of intestinal flora diversity showed that the diversity of intestinal flora in FZLZD group was significantly higher than that of model group. Conclusions: FZLZD can regulate gastric ulcer by promoting the expression of ZO-1 and Occludin and improving the diversity of intestinal flora. Keywords: Fu Zi Li Zhong Decoction (FZLZD) Gastric ulcer, ZO-1, Occludin, Intestinal flora diversity, 16SrDNA

Immediate mandibular reconstruction is always necessary for the patients receiving segmental mandibulectomy to recover the facial contour and function of occlusion. When 3D modeling is unavailable, temporary external fixator is necessary to maintain the occlusion relationship and facial contour. In this study, we introduce the clinical application of temporary external fixator for immediate mandibular reconstruction in patients receiving segmental mandibulectomy, which consists of 2 anchor claws, 2 all-round retentive arms, and 1 central locking structure. From August 2016 to September 2017, temporary external fixator was applied in 13 patients. Clinical data of gender, age, surgical procedure, duration of operation, and clinical outcomes were recorded and analyzed. Among the 13 patients, there were 4 men and nine women whose ages ranged from 21 to 64 (mean 47.7) years old. There were 9 benign and 4 malignant lesions. All lesions expended at the buccal side of mandible. 12 fibular flaps and 1 vascularized iliac bone graft were used. The mandibular defect ranged from 6 to 14 (mean 10) cm. The operation duration of surgery ranged from 5 to 10 (mean 7) hours. All flaps survived with primary healing. The occlusion and facial contour were good, without significant changes of the length of mandibular body and width of mandible before and after surgery. No functional sequelae were noted at the donor sites. From these results, the temporary external fixator is easy to operate; the surgical procedure is simple and time-saving for surgeon when 3D modeling is unavailable. The indication for temporary external fixator usage is the mandibular lesion growing outward to cheek soft tissue.

Activation of the inflammatory signaling pathway is the most vital part of the pre-metastatic events of breast cancer. Platycodin D (PlaD) shows favorable pharmacological activities in anti-inflammatory and anti-tumor effect. The main purpose of this study was to survey the effects of PlaD on S100A8/A9-induced inflammation in mouse mammary carcinoma 4T1 cells. S100A8/A9 immunolocalization and expression in pre-metastatic lung tissue were assessed by immunofluorescence staining and ELISA. 4T1 cells were treated with 2.5 μg/mL recombinant S100A8/A9 heterodimer and 7.5, 10, or 12.5 μM of PlaD. After 24 h of incubation, cell viability, migration, and invasion were evaluated by CCK-8, wound-healing, and transwell assay, respectively. Nuclear translocation of NF-κB p65 was determined by immunostaining and western blot. The levels of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α were detected by ELISA. The results showed that S100A8/A9 was actively increased and released into the extracellular space during the pre-metastatic phase of breast cancer. PlaD treatment attenuated S100A8/A9-induced growth, migration, and invasion of 4T1 cells. Furthermore, PlaD decreased the levels of IL-1β, IL-6, and TNF-α by inhibiting nuclear translocation of NF-κB p65. In conclusion, this study demonstrated that PlaD inhibited S100A8/A9-induced inflammatory response in 4T1 cells by suppressing the expression of IL-6, IL-1β, and TNF-α via inhibition of NF-κB signaling pathways.

The purpose of our study was to evaluate the effect of the addition of Lactobacillus casei and Lactobacillus plantarum to Cheddar cheese on the antioxidant properties during its ripening time and after simulated gastrointestinal conditions. During the whole ripening time, the scavenging of DPPH and hydroxyl radicals both reached their maximum activity at the 16th week, while reducing power activity was reached at the 20th week. The antioxidant values of probiotics cheese were significantly higher than that of control (p< 0.05). Similar results were found after simulated gastrointestinal conditions. The simulated gastric digestion can significantly reduce the activity of DPPH radicals-scavenging (p< 0.05), but after intestinal condition, the values came back to the same level compared with that before digestion. The electrophoretic patterns indicated that adding probiotic to cheese could promote the hydrolysis of protein to enhance the antioxidant activity, especially with mixed probiotics. The addition of probiotic bacteria to Cheddar cheese had nearly no effect on its composition, texture profile analysis, and sensory analysis.

Background and aims Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults. Methods and results The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]). Conclusions This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.

OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. OBJECTIVE To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. DESIGN Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF-GARFIELD-AF). SETTING 1317 participating sites in 35 countries. PARTICIPANTS 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks' duration) and at least one investigator determined stroke risk factor. MAIN OUTCOME MEASURES Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. RESULTS 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. CONCLUSION In this large dataset of patients with recent onset non-valvular atrial fibrillation, a small proportion were treated with cardioversion. Direct current cardioversion was performed twice as often as pharmacological cardioversion, and there appeared to be no major difference in outcome events for these two cardioversion modalities. For the overall cardioversion group, after adjustments for confounders, a significantly lower risk of mortality was found in patients who received early cardioversion compared with those who did not receive early cardioversion. STUDY REGISTRATION ClinicalTrials.gov NCT01090362.

Several studies have suggested that fibroblast-like synoviocytes (FLSs) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to evaluate the function of miR-6089 in the regulation of RA-FLSs. The levels of miR-6089 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the healthy synovial tissues and FLSs. The miR-6089 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell apoptosis accompany with an increase protein expression of cleaved-Caspase-3, -8 and -9. Furthermore, CCR4 was determined to target miR-6089 directly, and its expression was significantly increased in the synovial tissues of RA than in the healthy synovial tissues. The overexpression of CCR4 reversed the effect of miR-6089 on proliferation and apoptosis in RA-FLSs effectively. In conclusion, our study suggests that the miR-6089 may be a potential target for prevention and treatment of RA.

The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (Prevotellaceae, Fusobacteriaceae, Flavobacteriaceae, Lachnospiraceae, Peptostreptococcaceae, and Campylobacteraceae) and 13 genera, including Fusobacterium, Alloprevotella and Porphyromonas. At the species level, the abundances of Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter segnis, Capnocytophaga leadbetteri, Peptostreptococcus stomatis, and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).

This study was aimed at evaluating Lactobacillus rhamnosus for its ability to affect the antioxidant activity of Cheddar cheese during ripening and digestion. The effect of probiotic on the proteolytic patterns and antioxidant activity of Cheddar cheese during ripening was analysed. Three fractions (>10 kDa, 3–10 kDa, and

Background Astrocytes are the most abundant glial cells in a brain that mediate inflammatory responses and provide trophic support for neurons. We have previously disclosed that paroxetine, a common selective serotonin reuptake inhibitor, ameliorates LPS-induced microglia activation. However, it remains elusive for the role of paroxetine in astrocytic responses. Methods Isolated primary astrocytes were pretreated with paroxetine and stimulated with different stimuli, lipopolysaccharide (LPS) or microglia conditioned medium pre-activated with LPS (M/Lps). Inflammatory and neurotrophic responses, underlying mechanisms and the impact on neuronal survival were assessed. Results Paroxetine had no impact on LPS-stimulated iNOS, TNF-α, and IL-1β expression, but inhibited M/Lps-induced TNF-α and IL-1β expression in primary astrocytes. Paroxetine suppressed M/Lps- but not LPS-induced activation of NF-κB and had no impact on the activation of MAPKs and STAT3. Incubation with the resulted astrocyte conditioned media caused no change in the viability of SH-SY5Y cells. BDNF and MANF mRNA expressions were upregulated by M/Lps and paroxetine, respectively. However, M/Lps- or LPS-induced extracellular releases of NO, TNF-α, and/or BDNF in astrocytes were in minor amount compared to those by microglia. Conclusions Paroxetine ameliorates the reactive microglia-mediated inflammatory responses in astrocytes partially via inhibition of the NF-κB pathway but has no impact on LPS-stimulated astrocyte activation. While the effects of paroxetine on secondary astrocytic responses are not robust compared to its effect on the innate immune responses of microglia, the results together may implicate a therapeutic potential of paroxetine against neuroinflammation-associated neurological disorders such as Parkinson’s disease.

The present study aimed to identify the effects of arsenic on behaviors in Caenorhabditis elegans (C. elegans) and the transgenerational effects. The synchronized C. elegans (P generation) were exposed to 0, 0.2, 1.0, and 5.0 mM NaAsO2 and the subsequent generations (F1 and F2) were maintained on fresh nematode growth medium (NGM). The behaviors and growth were recorded at 0, 12, 24, 36, 48, 60, and 72 h post synchronization. The results demonstrated that arsenic affected various indicators regarding the behavior (head thrash, body bend, movement speed, wavelength, amplitude and so on) and in general the effects started to accumulate from 24 h and lasted throughout the exposure. The behavior impairments were transgenerational with varying patterns, amongst the head thrash and body bend responded most sensitively though the responses gradually declined across generations. Arsenic exposure inhibited the growth (body length, body width, and body area) in P C. elegans from 24 h to 60 h, however there was no difference between treatments groups and the control at 72 h. Arsenic led to a dose-dependent degeneration of dopaminergic neurons in C. elegans, and inhibition of BAS-1 and CAT-2 expressions. The expressions of GCS-1, GSS-1, and SKN-1 were induced by arsenic exposure. Overall, chronic arsenic exposure impaired the behaviors and there were transgenerational effects. The head thrash and body bend responded most sensitively. Arsenic induced behavioral disorders might be attributed to degeneration of dopaminergic neurons which was associated with oxidative stress.

BACKGROUND Platelet-derived growth factor alpha (PDGFRA) is a gene encoding tyrosine kinase receptor and both EGFR and PDGFRA activate tyrosine kinases. The implication of PGFRA in many cancers and its prognostic significance irrespective to EGFR status in spinal chordoma, gliomas, and uterine cancers have shown a need for its investigation in oral squamous cell carcinoma (OSCC). We investigated the prognostic value of PDGFRA mRNA expression in OSCC. PATIENTS AND METHODS The study was conducted in the department of oral maxillofacial surgery-head and neck oncology, at a tertiary hospital. The data on PDGFRA mRNA expression and immunohistochemical staining status in primary OSCC patients treated for curative surgery from 2010 to 2012 were analyzed. Univariate and multivariate analyses were performed with other cofactors for survival. RESULTS A total of 114 consecutive patients with primary OSCC who received treatment were studied. Thirty-one patients died of the disease. Strong PDGFRA immunohistochemical staining and high expression of PDGFRA mRNA were associated with positive pN status (P

To observe the clinical effect of lower-reinforcing and upper-reducing acupuncture method for hyperplasia of mammary gland (HMG) and its influence on estradiol (E2) and progesterone (P). A randomized, single-blinded and controlled trial was conducted. A total of 124 cases conforming to the inclusion criteria were randomized by random number table into a treatment group and a control group, with 62 cases in each group. Patients in both groups received acupuncture therapy at the same acupoints, while patients in the treatment group received lower-reinforcing and upper-reducing method, and patients in the control group received even reinforcing-reducing manipulation. The treatment started around 10 d before menstruation and was conducted every other day. Patients received 5 treatments in each menstruation cycle for consecutive 3 cycles. The levels of E2, P and E2/P and clinical efficacy were measured before and after treatment. After treatment, the breast lump size, pain intensity and concomitant symptoms score in both groups were substantially lower than those before treatment, showing statistical significances (all P 0.05). Lower-reinforcing and upper-reducing acupuncture method can effectively alleviate clinical symptoms and signs in HMG patients, and produce a better effect than even reinforcing-reducing manipulation. The majority of HMG patients’ E2, P level and E2/P value were not beyond the normal ranges; therefore, acupuncture showed no substantial influence on E2 and P levels and E2/P value.

Purpose The aim of the study is to comprehensively analyze the clinical epidemiology of the mandibular fracture including several factors which could affect the incidence, treatments, and outcomes of the mandibular fracture. Materials and methods A retrospective study was conducted to include the patients with mandibular fractures in the department of maxillofacial surgery of the Lanzhou University second hospital from 2011 to 2015. The predictor variables were age, gender, ethnicity, medical health, habits, etiology, and treatment methods for mandibular fracture. The outcome variables were postoperative complications of MFs and corrective revision surgeries. T, Chi-square, Fisher’s exact, and Spearmen statistical tests were used to analyze the data. Results There were 342 patients with 571 fractures. Male/female ratio was 4.1:1 with the third decade accounted for (30.1%). Traffic accidents (43.6%) were the most common etiology followed by falls (31.6%). Symphysis/parasymphysis (26.4%) and condyle (24%) were the most common fracture sites. The complication rate was 18.4% with the infection (8.8%), and malocclusion (5.8%) were the most frequent complications. The rate of secondary operation was (5%). A high time interval to repairing was detected (mean = 11.04) without statistical significance between the rate of the overall complications and time interval to repairing (P = 0.957). Compromising factors significantly increase the rate of infection. There was no significant difference between the administration of antibiotics and the incidence of infection (P = 0.289). Conclusion A well understanding of the epidemiology of mandibular fracture and variables’ correlations is clinically important in advancing the prediction, diagnosis, treatment, and prevention of mandibular fractures in a particular population. Potential risk factors such as trauma severity, compromised medical health, and patient’s behaviors were significantly affecting the resultant outcome. Open reduction and internal fixation of condyle fracture resulted in constant occlusal result than closed one. An antibiotic therapeutic effect against infection in mandibular fractures remains suspected. Time elapsing from injury to treatment had no influence on the overall complications.

We tested the hypothesis that genetic variation in ATM and BMI‐1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer‐free controls of Han nationality. This was an observational, hospital‐based, case–control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy‐Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene were significantly higher in cases than in controls (P = .005

Background Venous thromboembolism (VTE) is a preventable complication in which early ambulation is expected after head and neck surgery. Thus, the role of VTE prophylaxis is questionable and needs further assessment. The purpose of this study was to specify the relative contributing risk factors for patients who underwent head and neck cancer ablation with immediate reconstruction. Methods A retrospective analysis was conducted of consecutive head and neck cancer ablations with immediate reconstructions between 2008 and 2013. Dextran and prostaglandin E2 (PGE2) were routinely given as flap thromboprophylaxis. Logistic regression was applied to analyze the potentially significant risk factors. Results Of 1953 subjects, the incidence of symptomatic VTE was 2.2% with 0.1% mortality rate. Prolonged surgery (>592.5 minutes; P = .048), immobilization (>4 days; P = .019), and subjects without postoperative flap thromboprophylaxis (P = .002) are significant risk factors for VTE development. Conclusion Our flap thromboprophylaxis regime might have played a crucial role in keeping the incidence of VTE low. Despite prolonged immobilization in fibula flap reconstruction, the incidence of VTE remained low when flap thromboprophylaxis was given.

Hyperoside (quercetin-3-O-β-d-galactoside) is an active compound isolated from herbs. Neuroinflammation is a key mechanism involved in neurodegenerative disorders including Parkinson's disease. In this study, we aimed to investigate the potentiality of hyperoside in inhibiting microglia-mediated neuroinflammation. BV2 microglial cells were pretreated with hyperoside and stimulated with lipopolysaccharide (LPS). The results showed that hyperoside significantly inhibited LPS-induced production of nitric oxide and pro-inflammatory cytokines including IL-1β and TNF-α, as well as the expression of inducible nitric oxide synthase. Similar results were observed in primary microglial cells isolated from neonatal mice. Analyses in MAPK and NFκB signaling combined with specific inhibitors suggested that hyperoside attenuated the LPS-induced inflammatory responses via p38 and NFκB pathways. Furthermore, hyperoside suppressed reactive microglia-mediated neurotoxicity as evidenced by conditioned media culture, but had no direct impact on MPP+-induced toxicity in SH-SY5Y neuroblastoma cells. Collectively, our data suggest that hyperoside may serve as a protective agent by alleviating microglia activation in disorders such as Parkinson's disease.

The white blood cell (WBC) indices have been reported to have a prognostic impact in cancer of multiple organs including head and neck cancer; however; site and stage stratification was not attempted, and compelling evidence has shown that early cancers have a different distribution and prognostic ability than late-stage cancers. We studied the prognostic importance of WBC indices in early oral tongue cancers.The retrospective data of primary pT1N0 to pT2N0 oral tongue cancers treated between 2009 and 2013 were charted. WBC indices such as the neutrophil count, lymphocyte count (LC), platelet count (PC), and monocyte count, along with derived indices such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), were analyzed by multivariate analysis with other clinicopathologic prognostic factors.A total of 133 patients fulfilled the inclusion criteria; the minimum follow-up period for living patients was 36 months. A total of 22 patients reported disease relapse, and 11 patients died of disease. Multivariate analysis showed LC (hazard ratio [HR], 0.206; 95% confidence interval [CI], 0.092 to 0.46; P.001), PC (HR, 1.011; 95% CI, 1.001 to 1.021; P = .026), PLR (HR, 1.012; 95% CI, 1.008 to 1.016; P.001), and LMR (HR, 0.721; 95% CI, 0.596 to 0.872; P = .001) are significant independent prognostic factors for disease-free survival. Distant metastasis (HR, 9.014; 95% CI, 2.303 to 38.914; P = .004), LC (HR, 0.091; 95% CI, 0.015 to 0.558; P = .01), PC (HR, 1.023; 95% CI, 1.006 to 1.041; P = .009), PLR (HR, 1.016; 95% CI, 1.004 to 1.027; P = .002), and LMR (HR, 0.58; 95% CI, 0.387 to 0.868; P = .008) are significant independent prognostic factors for overall survival.Low pretreatment LMR and high PLR indicate poor survival in patients with early tongue cancer. We suggest close follow-up for this subgroup despite radical resection with clear margins.

The goal of the Collaborative Cross (CC) project was to generate and distribute over 1000 independent mouse recombinant inbred strains derived from eight inbred founders. With inbreeding nearly complete, we estimated the extinction rate among CC lines at a remarkable 95%, which is substantially higher than in the derivation of other mouse recombinant inbred populations. Here, we report genome-wide allele frequencies in 347 extinct CC lines. Contrary to expectations, autosomes had equal allelic contributions from the eight founders, but chromosome X had significantly lower allelic contributions from the two inbred founders with underrepresented subspecific origins (PWK/PhJ and CAST/EiJ). By comparing extinct CC lines to living CC strains, we conclude that a complex genetic architecture is driving extinction, and selection pressures are different on the autosomes and chromosome X. Male infertility played a large role in extinction as 47% of extinct lines had males that were infertile. Males from extinct lines had high variability in reproductive organ size, low sperm counts, low sperm motility, and a high rate of vacuolization of seminiferous tubules. We performed QTL mapping and identified nine genomic regions associated with male fertility and reproductive phenotypes. Many of the allelic effects in the QTL were driven by the two founders with underrepresented subspecific origins, including a QTL on chromosome X for infertility that was driven by the PWK/PhJ haplotype. We also performed the first example of cross validation using complementary CC resources to verify the effect of sperm curvilinear velocity from the PWK/PhJ haplotype on chromosome 2 in an independent population across multiple generations. While selection typically constrains the examination of reproductive traits toward the more fertile alleles, the CC extinct lines provided a unique opportunity to study the genetic architecture of fertility in a widely genetically variable population. We hypothesize that incompatibilities between alleles with different subspecific origins is a key driver of infertility. These results help clarify the factors that drove strain extinction in the CC, reveal the genetic regions associated with poor fertility in the CC, and serve as a resource to further study mammalian infertility.

BACKGROUND Platelet-derived growth factors alpha (PDGFA) is a tyrosine kinase receptor activator which is known to be amplified in the malignancies, and their expression levels are correlated to tumor progression and reduced overall survival. The expression of PDGFRA is different among the tumors and normal tissues; furthermore, their expression level is site specific. Under a physiological condition, PDGFRA and its ligand are expressed in distinct cell populations and activated in a paracrine manner. Nevertheless, heterodimer characteristic of PDGFRA allows it to be trans-activated by non-specific ligands or via autocrine manner. The future of cancer therapy can be based on PDGFRA receptor blockade and therefore warrants further investigation to determine the differing expression of PDGFRA between controls and patients with oral squamous cell carcinoma (OSCC). METHODS We performed a case-control study of 111 patients with newly diagnosed tongue squamous cell carcinoma and 111 control subjects without a cancer diagnosis, matched for age and gender, to evaluate the association between PDGFRA expression levels in oral mucosa. We then performed smoking stratification in each cohort. Independent t test analysis was applied for case-control comparisons. RESULTS Mean value of PDGFRA mRNA level (-ΔCt) for normal cohort is -30.242, whereas mean value of PDGFRA mRNA level for patients with OSCC is -11.516. PDGFRA mRNA level (-ΔCt) was significantly higher in oral cancer cohort, P

Tumor cells, including cancer stem cells (CSCs) resistant to radio- and chemotherapy, must enhance metabolism to meet the extra energy demands to repair and survive such genotoxic conditions. However, such stress-induced adaptive metabolic alterations, especially in cancer cells that survive radiotherapy, remain unresolved. In this study, we found that CPT1 (Carnitine palmitoyl transferase I) and CPT2 (Carnitine palmitoyl transferase II), a pair of rate-limiting enzymes for mitochondrial fatty acid transportation, play a critical role in increasing fatty acid oxidation (FAO) required for the cellular fuel demands in radioresistant breast cancer cells (RBCs) and radiation-derived breast cancer stem cells (RD-BCSCs). Enhanced CPT1A/CPT2 expression was detected in the recurrent human breast cancers and associated with a worse prognosis in breast cancer patients. Blocking FAO via a FAO inhibitor or by CRISPR-mediated CPT1A/CPT2 gene deficiency inhibited radiation-induced ERK activation and aggressive growth and radioresistance of RBCs and RD-BCSCs. These results revealed that switching to FAO contributes to radiation-induced mitochondrial energy metabolism, and CPT1A/CPT2 is a potential metabolic target in cancer radiotherapy.

Background: Sarcomas are a heterogeneous group of rare but deadly malignant tumors. The aim of this study was to comprehensively describe the incidence and mortality of sarcomas in Shanghai during 2002-2014. Method: Data were from Shanghai Cancer Registry. All new cases diagnosed with sarcomas and all death records where the cause of death listed as sarcomas were included. The characteristics of sarcomas incidence and mortality were analyzed. Age-standardized rates (ASRs) were adjusted by the world standard population. The trends were assessed by Joinpoint analysis. Results: A total of 9,440 incident cases were identified. The ASR was 3.4/105 for all sarcomas combined. Incidence of sarcomas overall was similar in females (3.5/105) as in males (3.4/105). Except for sarcomas "Not Otherwise Specified" (NOS), the most common histological subtype was gastrointestinal stromal sarcoma (GISS) (14.8%), which was followed by fibrosarcoma (7.2%), lipoblastoma (6.7%), leiomyosarcomas (6.5%), and osteosarcoma (5.3%). Among those incident cases, 87.9% were located in soft tissue sarcomas (STS) and 12.1% in bone and joint (bone sarcomas). The ASRs for STS and bone sarcomas were 2.8/105 and 0.6/105, respectively. Incidence rates for all STS combined rose exponentially with age, while bone sarcomas had the highest incidence at age 0-19. There were 4,279 deaths during 2002-2014 with the ASR of 1.3/105. Age-adjusted mortality due to sarcomas was slightly higher in males (1.5/105) than females (1.2/105). Except for sarcomas NOS, leiomyosarcomas was the most common subtype, comprising 9.9% of deaths due to sarcomas, followed by lipoblastoma (6.4%) and osteosarcoma (6.3%). The ASRs of mortality for STS and bone sarcomas were 1.0/105 and 0.2/105, respectively. For both males and females, the age-standardized incidence for STS and bone sarcomas did not change meaningfully over the study period. In contrast, age-standardized STS mortality in females increased by 2.3% per year (95% CI: 0.3, 4.4%), but was unchanged in males. No meaningful trends in bone sarcomas mortality were observed for either males or females. Conclusion: This population-based study was the first report of epidemiology of sarcomas in Shanghai according to anatomic site and histologic type. The diversity and rarity of sarcomas suggested more detailed data are warranted.

Introduction: Level of serotonin is mainly regulated by the serotonin reuptake transporter encoded by SLC6A4. The promoter region of SLC6A4 bears a repeat polymorphism 5-HTTLPR and a single nucleotide polymorphism rs25531. We have previously studied the association between these two variants and sporadic PD. The objective of the current study was to determine whether the SLC6A4 polymorphisms were associated with key motor and non-motor symptoms of PD. Methods: A total of 370 PD patients of Han Chinese were included. Associations between the SLC6A4 polymorphisms and PD symptoms including depression, intellectual impairment, tremor and rigidity were analyzed. Results: 5-HTTLPR was associated with depression in PD patients and presence of the LL genotype was protective against the depression risk. The rs25531 was associated with rest tremor in PD and the A allele serves as a recessive risk allele. No associations were found in the two polymorphisms with respect to intellectual impairment and rigidity in the cohort. Conclusion: The current study reveals two PD symptoms associated with SLC6A4 polymorphisms, and provides new insight into how serotonergic system genetically participates in the symptomatic progression of PD. Further study is warranted in additional populations.

Background: Parkinson's disease (PD) is a common and complex neurodegenerative disease with an elusive etiologies. Both molecular mechanisms and biomarkers remain to be further uncovered in PD. Methods: Qualified human microarray datasets of the substantia nigra and blood were acquired from PD case-control studies. A discovery and replication two-phase method was used to identify dysregulated genes with functional enrichment analyses. An integrated analysis was used to screen PD biomarkers followed by validations in blood samples of 50 PD patients and 50 controls. Findings: Eight datasets of substantia nigra and 3 datasets of blood were retrieved, including 21 million data points from 146 substantia nigra and 571 blood samples. A total of 5 up-regulated genes and 91 down-regulated genes (fold-change > 1.5 and P 1.2 and P < 0.05. TUBB2A in reduced expression decently predicted PD as a blood biomarker (sensitivity, 0.72; specificity, 0.70; AUC, 0.730 [95% CI, 0.632-0.828]). Interpretation: Our study provides novel insight into elucidating mechanisms underlying PD pathophysiology and the development of promising PD biomarkers. Funding: This work was supported by funding from Zhejiang Provincial Natural Science Foundation (LD19H090001 and LZ19H090002), National Natural Science Foundation of China (81571087, 81771380, and 81771510), and Wenzhou Municipal Science and Technology Bureau (C20170003). Declaration of Interest: The authors declare that there is no actual or potential conflict of interest. Ethical Approval: All participants provided written informed consent. The study was approved by the ethics committee of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University.

Background: Lung cancer is the leading cause of cancer deaths in the world, and more and more treatment modalities have been introduced in order to improve patients’ survival. For patients with advanced non-small cell lung cancer (NSCLC), survival prognosis is poor and multimodality neoadjuvant therapies are given to improve patients’ survival. However, the possibility of occult metastases may lead to discrepancy between clinical and pathologic staging and underestimation of the disease severity. This discrepancy could be the reason for poor survival prediction reported by previous studies which conducted their analysis from the point of view of clinical stage. The aim of this study was to analyze the relationship between clinico-pathologic factors and survival from the pathologic point of view and to try to identify survival prognostic factors. Methods: From January 2005 to June 2011, 88 patients received neoadjuvant therapy because of initial locally advanced disease, followed by anatomic resection and mediastinal lymph node (LN) dissection. All their clinico-pathologic data were collected from a retrospective review of the medical records and subjected to further analysis. Results: We found that total metastatic LN ratio (P=0.01) and tumor size (P=0.02) were predictive factors for disease free survival (DFS). We used these two prognostic factors to stratify all patients into four groups. Group 4 (tumor size ≤5, total metastatic LN ratio ≤0.065) had the best DFS curve, while the DFS curve progressively deteriorated across group 3 (tumor size ≤5, total metastatic LN ratio >0.065), group 2 (tumor size >5, total metastatic LN ratio ≤0.065) and group 1 (tumor size >5, total metastatic LN ratio >0.065). However, no definitive prognostic factor could be identified in this study. Conclusions: In conclusion, tumor size greater than 5 cm and total metastatic LN ratio greater than 0.065 could predict the DFS of patients with advanced NSCLC after multimodality therapies followed by surgical resection. Tumor size plays a more important role than total metastatic LN ratio in DFS. Moreover, patients identified with these factors need active post-operation surveillance and additional aggressive adjuvant therapies.

Ecto-5'-nucleotidase [cluster of differentiation (CD)73] has important functions in several types of cancer, however, its expression in squamous cell carcinoma (SCC) remains unknown. The present study was designed to investigate CD73 expression in SCC. CD73 expression was assessed by immunohistochemistry in 113 patients with oral SCC (OSCC). The association between CD73 expression and clinicopathological features, overall survival (OS) and disease-free survival (DFS) times of patients were statistically analyzed. CD73 expression was detected in 58.4% (66/113) of OSCC patients, with the immunostaining predominantly localized in the cytomembrane and a little in the cytoplasm. Statistical analysis revealed that CD73 expression was more frequently detected in patients with larger tumors (P=0.021). The overexpression of CD73 was significantly associated with clinical stage (P=0.047). Furthermore, immunohistochemical staining showed that overexpression of CD73 was inversely correlated with DFS (P=0.002) and OS (P=0.002) times. Multivariate Cox regression analysis revealed that CD73 expression was an independent prognostic factor for poor DFS (P=0.018) and OS (P=0.021). The current study is the first to evaluate the clinical significance and prognostic value of CD73 in patients with OSCC. The findings suggest that CD73 is a potential prognostic marker for OSCC.

Background The current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response. Methods We initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS). Results The 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P

MicroRNA-455 (miRNA-455), which is downregulated in human cancer, potently mediates the multiple steps of carcinogenesis. However, the role of miR-455 in non-small cell lung cancer (NSCLC) carcinogenesis remains unclear. In present study, we determined the mature miRNA-455 expression in NSCLC tissues and cells by real-time PCR. Follow-up studies examined the effects of a miR-455 mimic (gain of function) on cell proliferation, migration, and invasion. Our data indicate that miR-455 was significantly down-regulated in NSCLC cell lines and tissues. In functional assays, overexpression of miR-455 suppressed the proliferation, migration, and invasion of NSCLC cell lines. Data from reporter assays showed that miR-455 directly binds to 3'UTR of ZEB1 and suppresses the endogenous level of ZEB1 protein expression. Furthermore, overexpression of ZEB1 reverses miR-455-suppressed malignant phenotype of NSCLC cells. Moreover, we found that upregulation of ZEB1 expression is inversely associated with miR-455 expression in NSCLC tissues. Taken together, miR-455 as an anti-oncogene in non-small cell lung cancer through up-regulation of ZEB1 and serve as a potential therapeutic target in NSCLC.

Oral squamous cell carcinomas (OSCCs) are a growing problem in the world. The various existing treatments have not markedly improved the survival rate of patients with OSCC during the past three decades. Novel treatment strategies are required. Sex determining region Y-box 2 (SOX2) is a transcription factor that is involved in the maintenance of embryonic stem cell pluripotency and in multiple developmental processes. SOX2 expression was indicated to act as a prognostic factor in various types of tumors, including breast, colorectal, gastric and lung cancer and glioblastoma, and as a link between malignancy and stemness. Cancer stem cells (CSCs) may be responsible for the genesis, growth and metastatic spread of tumors. The poor survival outcomes for OSCC patients may be attributable to a poor selection of target cells for treatment, as current oral cancer therapies are generally aimed at the global mass of tumor. Therefore, the consideration that novel approaches to oral cancer may be targeted using SOX2 and CSCs appears reasonable. In order to better understand the oncogenic roles and the corresponding signal transduction pathways of the SOX2 protein, the present study emphasizes the role of SOX2 in OSCC, including the proteins associated with OSCC, and reviews the literature regarding the role of SOX2 in lymph node metastasis. The aim of the present study is to provide a reference for future studies that engage in research on the aforementioned subject.

Objective To investigate the epidemiology of cerumen impaction among children of municipal kindergartens in Wuhan. Methods The ear canal of children of municipal kindergartens in Wuhan was examined using an electric otoscope by the same otologist in 2005, 2006 and 2012, with age, gender, ears and the nature of cerumen (dry cerumen or wet cerumen) recorded. A chi-square test was performed to investigate for significant differences between cerumen impaction rates and the recorded variables. Results A total of 1,214, 1863 and 5205 children were examined in 2005, 2006 and 2012, and cerumen impaction prevalence rates for each year were 17.2%, 15.4% and 10%, respectively. Prevalence of cerumen impaction was significantly lower in 2012 than in 2005 or 2006. In 2005, dry cerumen impaction accounted for 22.2% of the total dry cerumen, while wet cerumen impaction only accounted for 5% of the total wet cerumen, showing a statistically significant difference. Conclusion The prevalence of cerumen impaction among children of kindergartens in Wuhan is higher than 10%, and children with dry cerumen are more prone to cerumen impaction. Annual otological examination of kindergarten children is recommended. And improved community ear health promotion activities should reduce the avoidable prevalence of cerumen impaction in pediatric population.