[Diagnosis and treatment of otogenic sigmoid sinus thrombophlebitis].

Objective:To summarize and analyze the clinical data of sigmoid sinus thrombophlebitis and discuss its treatment strategy. Methods:The clinical manifestations, auxiliary examinations, surgical procedures and anticoagulant therapy of patients diagnosed with otosource sigmoid sinus thrombophlebitis in the Department of Otorhinolaryngology, People's Hospital of Xinjiang Uygur Autonomous Region from November 2014 to November 2021 were retrospectively analyzed. Results:Five patients had a history of otorrhea and hearing loss for more than 5 years. They had headache during the acute episode, and 4 patients had drosive fever. They had severe complications, including brain abscess, sepsis, septic shock, intracranial hemorrhage, and hemorrhagic disseminated pneumonia. HRCT of temporal bone showed defects in the sigmoid sinus wall in 4 cases, and gas accumulation around and inside the sigmoid sinus in 3 cases. T1WI showed low signal, isosignal, and high signal in the sigmoid sinus area on MRI, and T2WI showed high signal in the sigmoid sinus area. The transverse sinus, sigmoid sinus and internal jugular vein were not developed in 2 cases, and the transverse sinus and sigmoid sinus were not developed in 1 case, and the internal jugular vein was thin. All 5 cases underwent radical mastoidectomy and resection of sigmoid sinus wall granulation or peritosinusitis abscess. The patients were followed up for 4-12 months and recovered well. Conclusion:For the cases of sigmoid sinus bone wall destruction accompanied by headache and fever by HRCT, it is necessary to be alert to the occurrence of sigmoid sinus thrombophlegitis, early diagnosis and early surgery to prevent the progression of the disease. Radical mastoidectomy combined with anti-infection therapy is the main treatment, and anticoagulation is necessary to achieve a better prognosis.

High-Throughput Sequencing Investigation of Bacterial Diversity in Chronic Suppurative Otitis Media and Middle Ear Cholesteatoma.

Background: Chronic otitis media is a common middle ear disease in otolaryngology. Bacterial infection is considered as the cause of the disease, but relying on conventional bacterial cultures can be problematic for identifying specific pathogens. Current research suggests that bacteria in microbial communities can only be identified by rDNA sequencing of bacteria. Methods: This cross-sectional study utilized broad-range PCR amplification of 16S rRNA genes with clone analysis to compare bacterial diversity in lesions from 6 patients with chronic suppurative otitis media (CSOM) and 10 patients with cholesteatoma of middle ear lesions. Bacteria were analyzed at the levels of phylum, order, family, genus, and species. Results: The age and sex difference between the patients with chronic suppurative otitis media and the patients with middle ear cholesteatoma were comparable (P > 0.05). Bacterial species abundance and species diversity were greater in cholesteatoma of the middle ear lesions than in CSOM lesions. The total number of detected operational taxonomic units (OTU) was 838, comprising 788 OTU detected in cholesteatoma pathological tissues, 230 in CSOM pathological tissues, and 180 OTU common to both groups. Proteus is a major part of CSOM (99.46%, P = 0.000321). The phyla detected in the Cholesteatoma samples were Proteus (Proteobacteria) (35.77%), thikum (Firmicutes) (44.21%, P = 0.001071), and Actinomycetes (Actinobacteria) (16.66%, P = 0.032464). At all bacterial taxonomic levels, the epithelial tissue of middle ear cholesteatoma was complex in terms of bacterial diversity, covering many Gram-positive and Gram-negative bacteria, likely related to bacterial microbiome formation. In contrast, the bacteriology of the CSOM lesions was relatively simple at all taxonomic levels, with all sequences characterized as belonging to Gram-negative bacteria. Conclusion: Our results suggest that persistent middle ear cholesteatoma infection may be a microbial flora disorder related to conditional pathogenic bacteria rather than a single bacterial infectious disease. The pathogen is relatively single in the diseased tissue of chronic suppurative otitis media, which is the main reason for its effective antiinfection treatment.

[Corrigendum] miR­490­5p regulates the proliferation, migration, invasion and epithelial­mesenchymal transition of pharyngolaryngeal cancer cells by targeting mitogen­activated protein kinase kinase kinase 9.

Following the publication of the above article, an interested reader drew to the authors' attention that the 'Control' and 'NC' data panels for the invasion assay experiments with the FaDu cell line in Fig. 5D on p. 248 contained apparently overlapping data, such that they may have been derived from the same source, even though they were intending to have shown the results from different experiments. On re­examining their original data, the authors have realized that they inadvertently included the data panel correctly shown as the 'NC' experiment for the 'Control' experiment as well. Subsequently, the authors re­examined their figures, and realized that both Figs. 4 and 5 contained additional data panels that had been assembled incorrectly. The authors elected to repeat these experiments in view of the errors made in assembling these figures, and the revised versions of Figs. 4 and 5 are shown on the next two pages. Note that the errors made during the assembly of these figures did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 240­252, 2019; DOI: 10.3892/ijmm.2019.4196].

Dichloroacetate attenuates the stemness of colorectal cancer cells via trigerring ferroptosis through sequestering iron in lysosomes.

Colorectal cancer stem cell (CSC) has been regarded to be the root of colorectal cancer progression. However, there is still no effective therapeutic method targeting colorectal CSC in clinical application. Here, we investigated the effects of dichloroacetate (DCA) on colorectal cancer cell stemness. We showed that DCA could reduce colorectal cancer cell stemness in a dose-dependent manner, which is evident by the decreased expression of stemness markers, tumor cell sphere-formation and cell migration ability. In addition, it was found that DCA trigerred the ferroptosis of colorectal CSC, which is characterized as the upregulation of iron concentration, lipid peroxides, and glutathione level, and decreased cell viability. Mechanistic studies demonstrated that DCA could sequester iron in lysosome and thus trigger ferroptosis, which is necessary for DCA-mediated attenuation on colorectal cancer cell stemness. Taken together, this work suggests that DCA might be a colorectal CSC-killer.

Silencing Nrf2 attenuates chronic suppurative otitis media by inhibiting pro-inflammatory cytokine secretion through up-regulating TLR4.

Compromised TLR-mediated chronic inflammation contributes to bacterial infection-caused chronic suppurative otitis media, but the mechanisms are unclear. The present study examined the expression status of nuclear erythroid 2-related factor 2 (Nrf2) and TLRs in human middle-ear mucosae tissues collected from patients with chronic suppurative otitis media, chronic otitis media and non-otitis media, and found that Nrf2 was high-expressed, whereas TLR4, instead of other TLRs, was low expressed in chronic suppurative otitis media compared to chronic otitis media and non-chronic otitis media groups. Consistently, inflammatory cytokines were significantly up-regulated in the chronic suppurative otitis media group, instead of the chronic otitis media and non-chronic otitis media groups. Next, LPS-induced acute otitis media and chronic suppurative otitis media models in mice were established, and high levels of inflammatory cytokines were sustained in the mucosae tissues of chronic suppurative otitis media mice compared to the non-otitis media and acute otitis media groups. Interestingly, continuous low-dose LPS stimulation promoted Nrf2 expression, but decreased TLR4 levels in chronic suppurative otitis media mice mucosae. In addition, knock-down of Nrf2 increased TLR4 expression levels in chronic suppurative otitis media mice, and both Nrf2 ablation and TLR4 overexpression inhibited the pro-inflammatory cytokine expression in chronic suppurative otitis media. Finally, we found that both Nrf2 overexpression and TLR4 deficiency promoted chronic inflammation in LPS-induced acute otitis media mice models. Taken together, knock-down of Nrf2 reversed chronic inflammation to attenuate chronic suppurative otitis media by up-regulating TLR4.

miR­490­5p regulates the proliferation, migration, invasion and epithelial­mesenchymal transition of pharyngolaryngeal cancer cells by targeting mitogen­activated protein kinase kinasekinase 9.

MicroRNA (miRNA/miR) has been identified to be a promising tool in treating pharyngolaryngeal cancer. The present study aimed to investigate the role of miR­490­5p in the regulation of proliferation, migration, invasion and epithelial­mesenchymal transition (EMT) of pharyngolaryngeal cancer cells. The data of miR­490­5p expression levels of 45 cases were obtained from the People's Hospital of Xinjiang Uygur Autonomous Region, and the prediction of the target of miR­490­5p was conducted by bioinformatics and verified using a luciferase assay. Cell viability was determined by cell counting kit­8. Migration and invasion rates were measured by wound healing test and Transwell apparatus, respectively. Colony formation rate was measured by plate colony formation assay. mRNA and protein levels were determined by quantitative polymerase chain reaction and western blotting, respectively. miR­490­5p expression was significantly depressed in primary pharyngolaryngeal cancer tissues and cell lines, leading to an unfavorable prognosis. Evidently, miR­490­5p overexpression decreased the cell viabilities of BICR 18 and FaDu cells. Mechanically, miR­490­5p could target mitogen­activated protein kinase kinasekinase 9 (MAP3K9). The overexpression of MAP3K9 could promote cell viability, migration and invasion rates, EMT process and ability of cloning, miR­490­5p could target MAP3K9 and further modulate the proliferation, migration, invasion and EMT of pharyngolaryngeal cancer cells. The results of the present study provide a novel entry point to the treatment of pharyngolaryngeal cancer.

miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in Crohn's disease.

Although aberrant microRNA (miRNA) expression has frequently been observed in inflammatory bowel disease (IBD), its biological functions and targets remain largely unknown. Present study found that miR-19b was significantly downregulated in active Crohn's disease (CD). Using bioinformatics analysis, suppressor of cytokine signalling 3 (SOCS3), a physiological regulator of innate and adaptive immunity that controls several immuno-inflammatory diseases, was predicted to be a potential target of miR-19b. An inverse correlation between miR-19b and SOCS3 protein levels, but not mRNA, was identified in active-CD intestinal tissue samples. By overexpressing or knocking down miR-19b in Caco2 cells and HT29 cells, it was experimentally validated that miR-19b is a direct regulator of SOCS3. Using a luciferase reporter assay, it was confirmed that miR-19b directly recognizes the 3'-untranslated region (3'-UTR) of SOCS3. Furthermore, overexpression of miR-19b decreased SOCS3 expression, leading to increased production of macrophage-inflammatory protein-3α (MIP-3α) in Caco2 cells. In contrast, knockdown of miR-19b increased SOCS3 and decreased MIP-3α. Finally, intracolonically delivered miR-19b decreased the severity of colitis induced with 2,4,6-trinitrobenzene sulphonic acid (TNBS). Taken together, our findings suggest that miR-19b suppresses the inflammatory response by inhibiting SOCS3 to modulate chemokine production in intestinal epithelial cells (IECs) and thereby prevents the pathogenesis of CD.

Elevated levels of Th17 cells and Th17-related cytokines are associated with disease activity in patients with inflammatory bowel disease.

OBJECTIVE: Interleukin-17(IL-17)-producing T helper(Th)17 cells are considered as a new subset of cells critical to the development of inflammatory bowel disease (IBD). We aimed to investigate the distribution of Th17 cells, the expressions of Th17-related cytokines (IL-17, IL-21 and IL-22) and their association with disease activity in IBD patients. METHODS: We collected intestinal tissue biopsies from 40 patients with active ulcerative colitis (UC), 20 patients with active Crohn's disease (CD) and 20 healthy controls. The distribution of Th17 cells and expressions of Th17-related cytokines in colonic tissues were evaluated by a standard immunohistochemical procedure. Serum IL-17, IL-21 and IL-22 levels were determined by ELISA. Pearson's and Spearman's correlation analyses were performed to analyze the correlation between the number of Th17 cells, the expressions of Th17-related cytokines and disease activity index, endoscopic and histological grading, and CRP and PLT levels, respectively. RESULTS: Compared with healthy controls, the number of Th17 cells and the expressions of IL-17, IL-21 and IL-22 were significantly increased in active IBD patients (P < 0.05). In addition, Pearson's and Spearman's correlation analyses showed that the number of Th17 cells and the expressions of Th17-related cytokines were correlated with disease activity index, endoscopic and histological grading, CRP and PLT levels (P < 0.05). CONCLUSIONS: Th17 cells and Th17-related cytokines (IL-17, IL-21 and IL-22) were increased in the intestinal mucosa in active IBD patients and may play an important role in disease activity and mucosal damage.

[Bacteriology of ethmoidal sinus in chronic rhinosinusitis with and without nasal polyps].

OBJECTIVE: To compare the bacteriologic features of anterior ethmoidal biopsy specimens between chronic rhinosinusitis without nasal polyps (CRSNP-), chronic rhinosinusitis with nasal polyps(CRSNP+) and control patients. METHOD: The biopsy specimens obtained during the nasal endoscopic surgery were cultured for aerobic and anaerobic bacteria. RESULT: One hundred and nineteen biopsy specimens were processed for homogenization and semiquantitatively bacterial culture of aerobe and anaerobe. Bacterial culture were positive in 104 specimens (total culture-positive rate was 87.4%). The positive rate of aerobe or facultative anaerobe culture were 86.5%, 85.7%, 90.0% in CRSNP- group, CRSNP+ group and control group, respectively. There were no significant differences between 3 groups (P > 0.05). Mixed growth of aerobe and anaerobe bacteria were mainly detected in the biopsy specimens and the positive rate were 78.4%, 81.0% and 85.0% in CRSNP- group, CRSNP+ group and control group. There were no significant differences in 3 groups (P > 0.05). The most common aerobe bacteria found in 3 groups were coagulase-negative staphylococci and corynebacterium species and there were no significant differences between 3 groups (P > 0.05). The positive rate of anaerobic bacteria culture were 78.4%,76.2% and 77.5% in 3 groups. There were no significant differences between the groups (P > 0.05). Propionibacterium and peptostreptococcus species were the most common anaerobes, and there were no significant differences between 3 groups (P > 0.05). CONCLUSION: There are no significant differences in the bacteriologic features of ethmoidal biopsy specimens between CRSNP+, CRSNP- and control patients. Therefore, bacterial infection may not play a key role in the pathogenesis of nasal polyps in CRS patients.