Dimethyl fumarate attenuates MSU-induced gouty arthritis by inhibiting NLRP3 inflammasome activation and oxidative stress.

OBJECTIVE: Dimethyl fumarate (DMF) has shown anti-inflammatory and antioxidant activities. However, the effects of DMF on gouty arthritis remain elusive, and the underlying mechanism is not understood. In this study, we aim to investigate the role of DMF in gouty arthritis. MATERIALS AND METHODS: Mice were gavage with DMF for consecutive 7 days at two different doses (10 mg/kg/day or 30 mg/kg/day, once daily) in advance and then monosodium sodium urate (MSU) was injected into their joint to establish an acute gout mice model. The pain and swelling of the hind paw in mice were determined. The production of pro-inflammatory cytokine in the paw tissues was assessed by Elisa and the inflammatory infiltration of the joint was determined by hematoxylin and eosin (H&E) staining. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the tissues were measured by commercial kits. In addition, the expression of nuclear factor kappa B (NF-κB) and NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome and downstream genes were detected by PCR and Western blot. Furthermore, LPS-primed murine macrophages Raw 264.7 cells were treated with different concentrations of DMF (2 µM, 5 µM, 10 µM) for 2 h, and then challenged with MSU (200 µg/mL) for other 12 h to observe the effect of DMF on cell viability via cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) levels in the supernatant of culture medium. Immunofluorescent staining was used to detect the NLRP3 inflammasome activation and reactive oxygen species (ROS) production in vitro. Caspase-1 activity was measured by corresponding assay kits both in vivo and in vitro. RESULTS: DMF attenuated pain and swelling in MSU-induced gout mice by decreasing pro-inflammatory cytokine production and inflammatory cell infiltration, as well as improved oxidative stress. Moreover, DMF inhibited the activation of NF-κB and NLRP3 inflammasome and subsequent expression of caspase-1, interleukin-1ß (IL-1ß), and IL-18 at both mRNA and protein levels. Meanwhile, DMF suppressed NLRP3 inflammasome expression and ROS production in LPS and MSU-stimulated Raw 264.7 cells, thereby protecting the cells from inflammatory injury. CONCLUSIONS: DMF serves as a new approach for the treatment of MSU-induced gouty arthritis by suppressing NLRP3 inflammasome activation and oxidative stress.

MiR-296-5p inhibits cell invasion and migration of esophageal squamous cell carcinoma by downregulating STAT3 signaling.

OBJECTIVE: Many studies have emphasized the function of microRNA-296 (miR-296) that inhibits tumor formation. To some extent, the role of miR-296 in esophageal squamous cell carcinoma (ESCC) remains misleading. Therefore, the current research was designed to investigate the regulatory mechanisms of miR-296 and signal transducer and activator of transcription 3 (STAT3) in ESCC. PATIENTS AND METHODS: The mRNA expression of miR-296-5p and STAT3 in ESCC tissues or cell lines was measured via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The protein level of STAT3 was measured by Western blotting assay. The Luciferase reporter assay was used to verify the binding sites between miR-296-5p and STAT3. The transwell assay was employed to identify cell migration and invasion. RESULTS: Down-regulation of miR-296-5p was detected in ESCC tissues and cell lines (p<0.01). Additionally, miR-296-5p was found to target STAT3 directly. Functionally, up-regulation of miR-296-5p or down-regulation of STAT3 significantly inhibited cell migration and invasion in ESCC. CONCLUSIONS: MiR-296-5p inhibited cell invasion and migration in ESCC by downregulating STAT3. The overexpression of miR-296-5p by targeting STAT3 suppressed tumorigenesis of ESCC cells.

[Acquired blood coagulation factor â ¤ deficiency in a patient with severe burn].

In March 2017, a severely burned male patient aged 36 years with hypovolemic shock was admitted to our hospital. The patient received large quantities of antibiotics and blood products and repeated skin graft after admission, and then he suffered wound errhysis and throat congestion. The patient was healthy before without family history of bleeding or thrombosis disease. Laboratory tests showed that prothrombin time and activated partial coagulation time were remarkably prolonged, blood coagulation factor Ⅴ activity was extremely low, and the result of qualitative test of coagulation factor inhibitor was positive. Acquired blood coagulation factor Ⅴ deficiency was diagnosed. After application of dexamethasone (5 mg, twice per day) and infusion of fresh frozen plasma, blood coagulation indicators of patients recovered in 4 days, the result of qualitative test of coagulation factor inhibitor was negative, and bleeding symptoms were improved.

[Clinical analyses of 263 patients with laryngeal leukoplakia].

Objective: To investigate the etiology, clinical and pathological characteristics of laryngeal leukoplakia and the predictive risk factors of recurrence and malignant transformation. Methods: Clinical data of 263 patients with laryngeal leukoplakia between January 2000 and December 2015 were analyzed retrospectively. Results: The pathological diagnoses included squamous epithelial hyperplasia (54.4%), mild dysplasia (17.9%), moderate dysplasia (12.2%), severe dysplasia and carcinoma in situ (12.5%), and invasive carcinoma (3.0%). Age and the extent of lesion were statistically different among different pathological groups (P<0.05). Gender, smoking and alcohol consumption did not show statistical differences among different pathological groups (P>0.05). Follow-up of 215 patients, excluding 6 cases of invasive carcinoma. The recurrence rate was 20.6%(43/209), and the malignant transformation rate was 5.3%(11/209). Multivariate analysis showed that pathological classification of moderate to severe dysplasia was the independent risk factor for recurrence and malignant transformation of laryngeal leukoplakia (P<0.05). In patients with severe dysplasia and carcinoma in situ, the recurrence proportion of conservative treatment, vocal cords (partial) resection and radiotherapy were 8/10, 0/10 and 2/11 respectively. Conclusions: Laryngeal leukoplakia occurs frequently in elderly men with long-term smoking history. Pathological diagnoses are different. The grade of dysplasia is the predictive risk factor for the recurrence and malignant transformation of laryngeal leukoplakia. More aggressive treatment and closer follow-up should be warranted for patients with moderate dysplasia, severe dysplasia and carcinoma in situ.

[Gastric glomus tumors expressing synaptophysin: clinicopathologic and immunohistochemical analyses].

Objective: To investigate the clincopathologic and immunohistochemical features of gastric glomus tumors and their differences from gastric neuroendocrine neoplasms. Methods: Six cases of gastric glomus tumors, 8 cases of glomus tumors in other sites and 7 cases of gastric neuroendocrine neoplasms were collected from the Department of Pathology, Taizhou Hospital. The clinicopathological and immunohistochemical characteristics of these tumors were analyzed retrospectively. Results: The gastric glomus tumors were located in the muscularis propria of the antrum and most cases strongly expressed synaptophysin (5/6). However, no synaptophysin expression was seen in glomus tumors of other organs.Most gastric neuroendocrine neoplasms were located in the mucosa or submucosa of the fundus and corpus. In addition to the strong expression of synaptophysin (7/7), CgA (6/7) and CD56(5/7) were strongly positive, although SMA was negative. Conclusions: Gastric glomus tumors and neuroendocrine neoplasms have similar morphological characteristics and both show strongly expression of synaptophysin. However, the location and immunohistochemical characteristics of gastric glomus tumors differ from those of the neuroendocrine neoplasms.

[Laryngeal endoscopic cricopharyngeal myotomy for cricopharyngeal achalasia post stroke].

Objective: To explore the safety and validity of endoscopic cricopharyngeal myotomy in patients with cricopharyngeal achalasia. Methods: A total of 19 patients with cricopharyngeal achalasia suffered from sustained dysphagia were enrolled in this study. The patients were divided into transcervical cricopharyngeal myotomy(CPM) group and endoscopic CPM (ECPM) group. Swallowing function and complications were evaluated.SPSS7.0 software was used to analyze the data. Results: The swallowing function improved significantly in seven patients in ECPM group, and 9 patients improved in CPM group.The video fluoroscopic swallowing study(VFSS)-swallowing score, VFSS-aspiration score and drinking test score were (3.1±1.1), (3.4±0.8) and (2.0±0.6)in post-ECPM, (3.4±1.4), (3.0±0.9) and (2.2±0.6)in post-CPM. No statistical difference was found in validity between CPM group and ECPM group(t=-0.435, t=1.086, t=-0.607, P>0.05). No statistical difference was observed on the occurrence of complication between two groups. Only one patient had subcutaneous emphysema after operation in ECPM. Conclusions: New surgical instruments and endoscopic surgical technique were safe and effective for cricopharyngeal achalasia. Because these instruments are cheaper, laryngeal endoscopic cricopharyngeal myotomy is easier to be popularized more easily than microscopic laser assistted CPM.

[Transoral coblation-assisted endoscopic minimally invasive surgery for superficial tongue base tumours].

Objective: To introduce the method of transoral coblation-assisted endoscopic minimally invasive surgery for superficial tongue base tumour. Methods: A total of 15 patients treated with transoral coblation-assisted endoscopic minimally invasive surgery from Mar. 2006 to Aug. 2016 were retrospectively reviewed. There were 9 patients with malignant tumors, 6 patients with benign neoplasms. Adjuvant postoperative radiation therapy was applied in three cases of squamous cell carcinoma, neck was performed in four cases of cancer. One case of non-Hodgkin lymphoma received postoperative chemotherapy. Results: One case with ectopic thyroid gland was treated by subtotal resection and one case with squamous cell carcinoma changed into open surgery because of major lingual artery bleeding. The En bloc resection under edoscope was achieved in 92.86%(13/14)of patients. Fifteen cases of neoplasms were followed-up for 8-50 months(median 20 months), one patient with Cowden syndrome was lost to follow-up because of appendical carcinoid combined pulmonary metastasis, one patient with non-Hodgkin lymphoma died of recurrence in other head neck areas 2 years after chemotherapy. Conclusion: Transoral coblation-assisted endoscopic surgery can successfully treat for the patients with superficial tongue base tumours.

Pollinators shift to nectar robbers when florivory occurs, with effects on reproductive success in Iris bulleyana (Iridaceae).

Studies have indicated that florivory and nectar robbing may reduce reproductive success of host plants. However, whether and how these effects might interact when plants are simultaneously attacked by both florivores and nectar robbers still needs further investigation. We used Iris bulleyana to detect the interactions among florivory, nectar robbing and pollination, and moreover, their effects on plant reproductive success. Field investigations and hand-pollination treatments were conducted on two experimental plots from a natural population, in which Experimental plot was protected from florivores and Control plot was not manipulated. The flower calyx was bitten by sawflies to consume the nectary, and three bumblebee species were pollinators. In addition, the short-tongued pollinator, Bombus friseanus, was the only robber when there was a hole made by a sawfly. The bumblebee had significantly shortened flower handling time when robbing, as compared to legitimate visits. Pollinator visitation and seed production decreased significantly in damaged flowers. However, seed production per flower after supplementary hand-pollination did not differ significantly between damaged and undamaged flowers. Compared to the Experimental plot, bumblebees visited fewer flowers per plant in a foraging bout in the Control plot. The flowers damaged by florivory allowed B. friseanus to shift to a nectar robber. Florivory and nectar robbing collectively decreased plant reproductive success by consuming nectar resources, which may reduce attractiveness to pollinators of the damaged flowers. However, the changes in pollinator behaviour might be beneficial to the plant by reducing the risk of geitonogamous mating.

[Expression difference of connexins in neural cells of Cx26 deficiency deafness].

Objective:Using induced pluripotent stem cell (iPSC) technology, neural cells from Cx26 deficiency deafness patients were derived, to investigate the influence of Cx26 deficiency on neural development and gene expression.Method:Fibroblasts were taken from profound deaf patients caused by Cx26 deficiency, and were induced to non-integration induced pluripotent stem cell lines, whose morphology, internal and external gene expression were characterized. Then these iPSC lines were differentiated into neural cells, whose expression change of pluripotent genes, neural markers and connexin genes were investigated.Result:Three iPSC lines with Cx26 deficiency were successfully established and differentiated into neural progenitor cells and neurons. The iPSC lines showed similar morphology, proliferation, internal and external gene expression with human embryonic stem cells. In iPSC-derived neurons, expression of Cx32 was up-regulated obviously, expression of Cx36 was up-regulated slightly, and expression of Cx26 showed no obvious change.Conclusion:TNeural differentiation of IPSC is not influenced by Cx26 deficiency, but expression of Cx32 and Cx36 are up-regulated, which may hint compensation from Cx32.

[Treatment of children's pharyngeal stenosis following pharyngeal surgery with coblation].

Objective:Pharyngeal stenosis as a postoperative complication following pharyngeal surgery (tonsillectomy/adenoidectomy) with coblation is rare and may be difficult to treat. This report is to explore the causes of pharyngeal stenosis and presents our successful treatment experience. Method:From Jan 2012 to July 2016, 5 children with pharyngeal stenosis (2 nasopharyngeal stenosis and 3 nasopharyngeal stenosis combined with oropharyngeal stenosis) secondary to pharyngeal surgery (tonsillectomy/adenoidectomy) in Peking Union Medical College Hospital were analyzed. Five cases with severe nasopharyngeal stenosis received surgery of scar resection, horizontal-to-vertical pharyngoplasty and local pharyngeal flap rotation; and three of them received free skin transplantation. After stenosis repair surgery, prolonged nasopharyngeal hollow stents were used for more than 6 months. To evaluate the therapeutic effect, pharyngeal cavities and symptoms of difficulty nasal breathing, mouth breathing, difficulty in blowing nose, hyponasal speech, snoring, restless sleep, anosmia, dysphagia were assessed and compared before and after surgery. Result:With 7-46 months follow-up, all symptoms of the 5 cases are ameliorated and the diameters of nasopharyx are more than 1.5 cm. No velopharyngeal insufficiency complication happened. Conclusion:Improper operation with coblation can cause severe pharyngeal stenosis. Flap rotation, horizontal-to-vertical pharyngoplasty and prolonged use nasopharyngeal hollow stents are reliable methods to correct pharyngeal stenosis following children's pharyngeal surgery.

Pathway crosstalk analysis in prostate cancer based on protein-protein network data.

Prostate cancer (PCa) is one of the major leading cause in men and no effective biomarkers or therapy have been approved for it to date. This study aimed to explore the molecular mechanisms and identify the potential molecular biomarkers of PCa. The microarray profile GSE38241 including 18 prostate cancer metastasis and 21 normal prostate samples was retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by Limma. DEGs functions were investigated by Gene Ontology (GO) and pathway enrichment analysis. Moreover, protein-protein interaction (PPI) network of DEGs was constructed, followed by functional analysis of modules. Additionally, pathway crosstalk network was constructed by integrating PPI network and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Totally, 334 up - and 703 down-regulated DEGs were identified. The functions of up-regulated DEGs were significantly enriched in GO terms of cell cycle phase and cell cycle process. While down-regulated DEGs mainly participated in actin filament-based process. Among these pathways in the pathway crosstalk network, T cell receptor signaling pathway, chemokine signaling pathways, endometrial cancer and glioma were found to play critical roles during PC progression. Cell division cycle 45 (CDC45), baculoviral IAP repeat containing 5 (BIRC5) and cell division cycle associated 5 (CDCA5) may be useful markers for predicting tumor metastasis and therapeutic targets for the treatment of PCa patients. Moreover, the pathway crosstalk network provides the groundwork that targeting multiple pathways might be more effective than targeting one pathway alone.

[Reliability and validity analysis of simplified Chinese version of QOL questionnaire of olfactory disorders].

Objective:To cross-culturally translate the questionnaire of olfactory disorders(QOD)into a simplified Chinese version, and evaluate its reliability and validity in clinical.Method:A simplified Chinese version of the QOD was evaluated in test-retest reliability, split-half reliability and internal consistency.Then it was evaluated in validity test including content validity, criterion-related validity, responsibility. Criterion-related validity was using the medical outcome study's 36-item short rorm health survey(SF-36) and the World Health Organization quality of life-brief (WHOQOL-BREF) for comparison. Result: A total of 239 patients with olfactory dysfunction were enrolled and tested, in which 195 patients completed all three surveys(QOD, SF-36, WHOQOL-BREF). The test-retest reliabilities of the QOD-parosmia statements(QOD-P), QOD-quality of life(QOD-QoL), and the QOD-visual simulation(QOD-VAS)sections were 0.799(P<0.01),0.781(P<0.01),0.488(P<0.01), respectively, and the Cronbach' s α coefficients reliability were 0.477,0.812,0.889,respectively.The split-half reliability of QOD-QoL was 0.89. There was no correlation between the QOD-P section and the SF-36, but there were statistically significant correlations between the QOD-QoL and QOD-VAS sections with the SF-36. There was no correlation between the QOD-P section and the WHOQOL-BREF, but there were statistically significant correlations between the QOD-QoL and QOD-VAS sections with the SF-36 in most sections.Conclusion:The simplified Chinese version of the QOD was testified to be a reliable and valid questionnaire for evaluating patients with olfactory dysfunction living in mainland of China.The QOD-P section needs further modifications to properly adapt patients with Chinese cultural and knowledge background.

[Transoral endoscopic minimally invasive surgery for hypopharyngeal postcricoid and upper esophageal lesions].

Objective:To describe the therapeutic effect of transoral endoscopic minimally invasive surgery for hypopharyngeal postcricoidarea and upper esophageal lesions. Method:Transoral endoscopic minimally invastive surgery was carried out in fifteen patients.There were 7 patients with primary tumors on the postcricoid area, including three squamous cell carcinoma（2 cases T2N0M0，1 case T2N2cM0），two cavernous hemangioma, one giant fibrovascular polyp and one recurrent lipofibroma. The transoral endoscopic tumors resection en bloc was performed in all of them. Adjuvant postoperative radiation therapy was applied in cases of cancer, and bilateral neck dissections was performed in the T2N2cM0 case; There were other eight patients with upper esophageal lesions , seven cases dysphagia was caused by stroke and one case was Zenker diverticulum, treated by endoscopic cricopharyngeal myotomy ordiverticulotomy. Result:The en bloc resection endoscopically was achieved in all of patients with tumors on the postcricoid area. All surgical resection margins were negative.The two cases of postcricoid cancer and four benign tumor were followed up 16-30 months and 2-12 months respectively, and all of the cases were not local recurrence. A recent patient with postcricoid cancer had not finished postoperative adjuvant radiation therapy. The endoscopic cricopharyngeal myotomy was effective in 4 out of 7 patients,nasogastric feeding was no longer required.Significant improvement occurred in Zenker diverticulotomy patient, due to the return of physiological deglutition, and Barium swallow study showing disappearance of the diverticulum after one month.The effects of minimally invasive threatment were satisfactory,such as not need tracheotomy and early oral feeding, shorter hospital stay and less postoperative complications. Conclusion:Transoral endoscopic surgery is minimally invastive, safe and effective treatment alternative for some hypopharyngeal postcricoid area and upper esophageal lesions.

Association between the interleukin-6-174 G/C polymorphism and risk of ischemic stroke: a meta-analysis.

Numerous studies have evaluated the association between the -174 G/C polymorphism in the interleukin-6 (IL6) gene and ischemic stroke risk. However, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association of the IL6 -174 G/C polymorphism with ischemic stroke. Published literatures from PubMed and Embase databases were retrieved. Pooled ORs with 95%CIs were calculated using fixed- or random-effect models. A total of seven case-control studies containing 2025 patients and 2174 controls were enrolled into this meta-analysis. In combined analysis, the results showed no significant association between the IL6 -174 G/C polymorphism and ischemic stroke risk in the overall population (GG vs CC: OR = 1.22, 95%CI = 0.50-3.01; TT vs TC: OR = 0.97, 95%CI = 0.81-1.15; dominant: OR = 0.98, 95%CI = 0.70-1.38; or recessive: OR = 1.24, 95%CI = 0.57-2.70) models. In the subgroup analysis by race, no significant associations between the -174 G/C polymorphism in the IL6 gene and ischemic stroke risk were found in Caucasians or Asians. No publication bias was found in the present study (all P > 0.05). Overall, the meta-analysis results suggested that the IL6 -174 G/C polymorphism was not associated with an increased risk of ischemic stroke. Further large and well-designed studies are needed to confirm this conclusion.

Heat shock protein 70 polymorphisms in Chinese patients with Graves' disease.

Graves' disease (GD) is a common autoimmune disease mainly affecting the thyroid. However, the correlation between the development of GD and HSP70 alleles has not been reported in the Chinese population. Therefore, the aim of this study was to investigate the association between HSP70 polymorphisms and GD in the Chinese population. A total of 153 patients with GD treated at the Yan'an Affiliated Hospital of Kunming Medical University between October 2010 and August 2013 were enrolled in this study; one hundred and twenty healthy volunteers were included in the control group. HSP70 polymorphisms at positions HSP70-1 +190, HSP70-2 +1267, and HSP70-hom +2437 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The distribution of the HSP70-2 +1267 GG genotype allele frequencies among GD and control subjects differed significantly (χ(2) = 20.40, P < 0.001; χ(2) = 18.18, P < 0.001). The G allele of HSP70-2 +1267 (Odds ratio = 0.455, 95% confidence interval: 0.315-0.655) conferred a higher risk of developing GD than the A allele. We observed no significant differences in the allelic frequencies of HSP70-1 +190 and HSP70-hom +2437. Therefore, the HSP70-2 +1267 GG genotype and the G allele may increase the risk of GD in Chinese subjects. The results of this study may be useful in identifying patients with increased risk of GD, and offer useful reference data for targeted gene therapy of GD in the future.

Longitudinal spin Seebeck effect free from the proximity Nernst effect.

This Letter provides evidence for intrinsic longitudinal spin Seebeck effects (LSSEs) that are free from the anomalous Nernst effect (ANE) caused by an extrinsic proximity effect. We report the observation of LSSEs in Au/Y(3)Fe(5)O(12) (YIG) and Pt/Cu/YIG systems, showing that the LSSE appears even when the mechanism of the proximity ANE is clearly removed. In the conventional Pt/YIG structure, furthermore, we separate the LSSE from the ANE by comparing the voltages in different magnetization and temperature-gradient configurations; the ANE contamination was found to be negligibly small even in the Pt/YIG structure.

Robust formation of Skyrmions and topological Hall effect anomaly in epitaxial thin films of MnSi.

Magnetotransport properties have been investigated for epitaxial thin films of B20-type MnSi grown on Si(111) substrates. Lorentz transmission electron microscopy images clearly point to the robust formation of Skyrmions over a wide temperature-magnetic field region. New features distinct from those reported previously for MnSi are observed for epitaxial films: a shorter (nearly half) period of the spin helix and Skyrmions, and a topological Hall effect anomaly consisting in ∼2.2 times enhancement of the amplitude and in the opposite sign with respect to bulk samples.

Electric-field control of nonvolatile magnetization in Co40Fe40B20/Pb(Mg(1/3)Nb(2/3))(0.7)Ti(0.3)O3 structure at room temperature.

We report a large and nonvolatile bipolar-electric-field-controlled magnetization at room temperature in a Co(40)Fe(40)B(20)/Pb(Mg(1/3)Nb(2/3))(0.7)Ti(0.3)O(3) structure, which exhibits an electric-field-controlled looplike magnetization. Investigations on the ferroelectric domains and crystal structures with in situ electric fields reveal that the effect is related to the combined action of 109° ferroelastic domain switching and the absence of magnetocrystalline anisotropy in Co(40)Fe(40)B(20). This work provides a route to realize large and nonvolatile magnetoelectric coupling at room temperature and is significant for applications.