Tumor necrosis factor α promotes HEp-2 cell proliferation via toll-like receptor 4 and NF-κB signaling pathways.

Laryngeal carcinoma is a serious, life-threatening disease. Tumor necrosis factor α (TNF-α), a proinflammatory cytokine, has complex effects on the proliferation and growth of cancer cells. Previously, we treated a laryngeal cancer cell line (HEp-2) with TNF-α and demonstrated that this treatment suppressed polycystin-2, a transient receptor potential cation channel expression and ATP-induced Ca2+ release but increased HEp-2 cell proliferation and growth. However, the mechanisms and signaling pathways underlying the TNF-α effects on the HEp-2 cells were unclear. Therefore, we here used RNA-seq techniques to examine the effect of TNF-α on the gene transcript expression profile in these cells. We found that TNF-α treatment (100 ng/mL, 24 h) upregulated 2,811 genes and downregulated 1,128 genes. The IRAK1 gene encoding an effector protein downstream of toll-like receptor 4 (TLR4) was ranked 19th in the upregulated differentially expressed genes. In a gene ontology (GO) analysis, 168 GO terms were identified in the biological process domain for the upregulated differentially expressed genes, and cell cycle and DNA replication functions were enriched. In a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, TNF-α treatment enhanced the NF-κB pathway in HEp-2 cells. Moreover, both the transcript and protein expression levels of TLR4 as well as the expression of genes encoding downstream TLR4 effectors were significantly increased in TNF-α-treated HEp-2 cells. We concluded that TNF-α increased HEp-2 cell proliferation and growth likely via enhancing TLR4- and NF-κB-associated signaling pathways and that TNF-α may play an important role in the development of laryngeal cancer.

Effects of wild type tau and disease-linked tau mutations on microtubule organization and intracellular trafficking.

We investigate the effects of transient expression of wild type (WT) and disease-linked mutations of tau (R406W, P301L, ΔN296) on cytoskeletal organization and cargo transport in COS-7 cells, which are natively tau-free. The introduction of tau proteins (either WT or mutant forms) leads to a dramatic restructuring of the microtubule cytoskeleton, as observed using immunofluorescence microscopy. Yet, this microtubule bundling and aggregation has a modest effect on the speed and travel distance of motor-driven cargo transport, as measured by the motions of fluorescently-labeled lysosomes. This suggests that localized transport events are insensitive to the global structure of the microtubule cytoskeleton. Importantly, we also found no evidence that the disease-linked tau mutants were particularly toxic; in fact we found that expression of mutant and WT tau had similar effects on overall microtubule structure and transport phenotypes.

[Evaluation on the hearing, speech and quality of life for cases received cochlear implant].

OBJECTIVE: Through the use of the categories of auditory performance (CAP-II), the speech, spatial and qualities of hearing scale-parents' version (SSQ-P), children using hearing implants quality of life (CuHI-QoL) in patients with prelingual hearing impairment to compare the rehabilitation effect between preoperative and postoperative auditory performance, speech behavior and quality of life and at the same time to figure out dose rehabilitation effect connected to age. METHOD: Mainly used classification method to compare the audotory performance, speech behavior and quality of life of 50 patients before and after 2.5 years after the implantation. At the same time these 50 patients are divided on the basis of the age received the surgery, A group received the surgery before 6(1.0-5.9) years old and group B received the therapy after this age (6.0-10.9). Their auditory performance, speech behavior and quality of life were all evaluated. RESULT: There were statistical difference between two kinds of classification method of CAP-II. In the study of SSQ-P and CuHI-QoL, there was no statistical difference in well-being and happiness before and 3 years after the implant, also there was no statistical difference in parental stress between two age groups. In addition to the above two, the rest all have statistical significance. CONCLUSION: After the implant, postoperative auditory performance, speech behavior and quality of life all had improved and the smaller the age, the better the performance.

[A questionnaires study on cochlear implantation in patients with white matter changes].

OBJECTIVE: This article evaluates the auditory and speech perception outcomes of sensorneural hearing loss with cerebral white matter abnormalities after cochlear implantation. METHOD: A retrospective analysis was performed on the cochlear implantatees with cerebral white matter abnormalities by using the categories of auditory performance and speech intelligibility rating, and compared with the non-syndrome patients with sensorineural hearing loss. Paired t-test was used for statistical analysis. RESULT: There was statistical difference between normal group and white matter changes group with sensorineural hearing loss after 6 month. No statistical difference was found after 12 month and 24 month. CONCLUSION: In the short term, the cochlear implant can be performed safely in patients with white matter changes. After a formal rehabilitation training,no significant difference in auditory or language ability was found between normal group and white matter changes group with sensorineural hearing loss.

[Middle ear cancer recurrence after operation+radiotherapy with adjacent tissue necrosis: two cases report].

Retrospective analysis of two cases of advanced carcinoma of the middle ear. Two patients underwent operation and radiotherapy. A case developed extensive necrosis in ear and neck, which finally led to lethal hemorrhage. Multiple relapse with cranial fossa invasion and extensive necrosis was found in the other case.

Tau proteins harboring neurodegeneration-linked mutations impair kinesin translocation in vitro.

We tested the hypothesis that mutant tau proteins that cause neurodegeneration and dementia differentially alter kinesin translocation along microtubules (MTs) relative to normal tau in vitro. We employed complementary in vitro motility assays using purified recombinant kinesin, purified recombinant tau, and purified bovine brain α:ß tubulin to isolate interactions among these components without any contribution by cellular regulatory mechanisms. We found that kinesin translocates slower along MTs assembled by any of three independent tau mutants (4-repeat P301L tau, 4-repeat ΔN296 tau, and 4-repeat R406W tau) relative to its translocation rate along MTs assembled by normal, 4-repeat wild type (WT) tau. Moreover, the R406W mutation exhibited isoform specific effects; while kinesin translocation along 4-repeat R406W tau assembled MTs is slower than along MTs assembled by 4-repeat WT tau, the R406W mutation had no effect in the 3-repeat tau context. These data provide strong support for the notion that aberrant modulation of kinesin translocation is a component of tau-mediated neuronal cell death and dementia. Finally, we showed that assembling MTs with taxol before coating them with mutant tau obscured effects of the mutant tau that were readily apparent using more physiologically relevant MTs assembled with tau alone, raising important issues regarding the use of taxol as an experimental reagent and novel insights into therapeutic mechanisms of taxol action.

[Multi-center study of clinical treatment on the flat type of sudden hearing loss].

OBJECTIVE: To investigate the effect of different treatment options for the flat type of sudden hearing loss. METHODS: Prospective, multi-center clinical study was carried out using internationally used standardized clinical research method. Patients with the flat type of sudden hearing loss between 18 and 65 years old, within two weeks duration, and without any medical treatment were recruited. Treatment options were randomly selected according to the designed random table. RESULTS: From August 2007 to October 2011, 402 patients with the flat type of sudden hearing loss who met the criteria (account for 39.26% of the total number of patients) from the 33 hospitals were collected; the total effective rate was 82.59%, and no significant difference was detected between different treatments, (χ(2) = 10.95, P = 0.28). In the 402 cases, 139 were cured (34.58%); 118 were markedly improved (29.35%); 75 were effective (18.66%); 70 were invalid (17.41%). CONCLUSIONS: The therapeutic efficacy of flat type of sudden hearing loss overall is good; the treatment of improving the inner ear blood rheology and/or reducing blood fibrinogen has clinical significance; the therapeutic efficacy of using glucocorticoid systemically is good as well; there is no obvious difference between combination and single medication.

Mechanical and functional properties of epothilone-stabilized microtubules.

Using a suite of biophysical tools, we assess the mechanical, structural, and functional properties of microtubules (MTs) stabilized by the chemotherapeutic compounds epothilone-A, epothilone-B, and taxol in vitro. We demonstrate that MTs stabilized by epothilone-A or epothilone-B are competent to bind tau proteins and support kinesin translocation. Kinesin speed is sensitive not only to the type of small molecule stabilizer used but also to the presence of the essential MT-associated protein tau. Epothilone-stabilized MTs are substantially less stiff than taxol-stabilized MTs. The addition of tau proteins to MTs stabilized by either epothilone compound or taxol further reduces stiffness. Taken together, these results suggest that small molecule stabilizers do not simply stabilize a "native" MT structure, but rather they modulate the structure, function, and mechanics of the MTs they bind. This may have important consequences to the therapeutic use of these agents in cancer chemotherapies.

Spectral analysis methods for the robust measurement of the flexural rigidity of biopolymers.

The mechanical properties of biopolymers can be determined from a statistical analysis of the ensemble of shapes they exhibit when subjected to thermal forces. In practice, extracting information from fluorescence microscopy images can be challenging due to low signal/noise ratios and other artifacts. To address these issues, we develop a suite of tools for image processing and spectral data analysis that is based on a biopolymer contour representation expressed in a spectral basis of orthogonal polynomials. We determine biopolymer shape and stiffness using global fitting routines that optimize a utility function measuring the amount of fluorescence intensity overlapped by such contours. This approach allows for filtering of high-frequency noise and interpolation over sporadic gaps in fluorescence. We use benchmarking to demonstrate the validity of our methods, by analyzing an ensemble of simulated images generated using a simulated biopolymer with known stiffness and subjected to various types of image noise. We then use these methods to determine the persistence lengths of taxol-stabilized microtubules. We find that single microtubules are well described by the wormlike chain polymer model, and that ensembles of chemically identical microtubules show significant heterogeneity in bending stiffness, which cannot be attributed to sampling or fitting errors. We expect these approaches to be useful in the study of biopolymer mechanics and the effects of associated regulatory molecules.

[Diagnostic diagnosis of thyroid microcarcinoma].

OBJECTIVE: To investigate how to improve the rate of clinically diagnosis of thyroid microcarcinoma. METHOD: Clinically diagnostic data of 73 cases with TMC, operated and confirmed by pathology from Jan. 2000 to Dec. 2009 were retrospective analyzed, the data were divided into A, B groups, A group (21 cases) can touch the regional lymph nodes and/or thyroid nodule with hard quality; B group(52 cases) can't touch the regional lymph nodes and/or thyroid nodule with hard quality, and the data was analyzed by statistical software. RESULT: Fifty-three cases diagnosed preoperatively and intraoperatively, the diagnosis rate was 73% (53/73). A group including 18 ca ses, diagnostic rate was 86% (18/21); B group including 35 cases, diagnostic rate was 67% (35/52); A variety of auxiliary examination and intraoperative exploration, etc, was statistically significant for improving the diagnostic rate of TMC. CONCLUSION: The clinically missed diagnostic rate of TMC was high, but the physicians adequate attention, careful palpation before surgery, the corresponding auxiliary inspection measures will help improve the clinically diagnostic rate of TMC.

[Application of lateral cervical incision in the removal of the cervical esophageal foreign body].

OBJECTIVE: To study the indication and clinical application of lateral neck incision for the removal of cervical esophageal foreign bodies. METHODS: From January 1999 to January 2009, 2189 cases esophageal foreign bodies were treated. The clinical data of 137 cases (6.25%) with lateral neck incision were retrospectively analyzed. In these 137 cases, 114 cases were over 16-years-old (adult group), while 23 cases were under 16-years-old (children group). In adult group, 67 cases (58.8%) had esophageal perforation (esophageal perforation with neck abscess 29 cases, esophageal perforation without neck abscess 38 cases); 47 cases did not have esophageal perforation (impacted foreign body without neck abscess 40 cases, foreign body with esophageal abscess 7 cases). In children group, 19 cases (82.6%) had esophageal perforation including 15 cases with neck abscess; 4 cases without esophageal perforation, 3 cases had esophageal abscess and one case without abscess but of huge foreign body. RESULTS: All 137 patients with foreign body were cured through lateral neck incision. Nineteen cases (13.9%) had hoarseness and recovered in 3 months. Five adult patients had post-operative cicatricial stricture of the esophagus, but it was mild and completely recovered by the treatment of dilatation in 3 to 11 months. Nine adult patients with esophageal perforation were cured by secondary suture, the remaining esophageal perforation cases were healed by first intention. One case with common carotid artery impairement by the foreign body was successfully treated by carotid artery ligation without hemiplegia, aphasia and other sequelae. Two cases had cardiopulmonary arrest, 2 cases had febrile convulsions and 1 case had acute respiratory failure, 5 cases had septic shock, all these patients were effectively controlled and cured. Seven of the 9 cases with tracheotomy had the tracheal tube removed during hospitalization; 1 of the two obese patients had the extubation 3 months after the discharge and the other one still had the tube. All esophageal perforation cases in children group had primary healing by perforation apposition suture. Four of the 5 children had successful tracheotomy decannulation, one child had extubation by 2 months through continuously reduced tracheal tube model. CONCLUSION: Penetrating esophageal foreign body and neck abscess were indication of the lateral neck incision, and positive prevention and cure the complications of lateral neck incision could achieve good curative effect.

[Clinical anatomical study of the adult lateral skull base].

OBJECTIVE: Through the observation and the measurements of the significant anatomical landmark the lateral skull base, to provide anatomical data of clinical location and navigation for surgery at the lateral skull base. METHOD: Significant anatomical landmarks of twenty adult cadaveric heads (40 sides) fixed in 10% formaldehyde and 20 operation cases (20 sides) had been observed and measured. Lateral skull bases of cadaveric heads were numbered from 1st to 40th, while the operation cases were numbered from 1st to 20th. RESULT: The anatomical data was achieved by measuring related anatomical landmark as follows: the distances between the significant landmark of the lateral skull base and the pars neuraxis, vein of the jugular foramen; the areas of trautmann triangle; post labyrinths triangle and the superficial triangle of processus mastoideus; the maximal distance of initiative displacement of facial nerve in the lateral skull base operations. CONCLUSION: The data measured at lateral skull base could effectively help operators not only to enlarge the field of vision in operations with security and to avoid the damagement of the important blood vessel and nerves, but also to retain the function of the facial nerve to the utmost.

[A clinical study of the influence on the drying of the ear canal by cleaning the focus of infection in the posterior tympanum].

OBJECTIVE: To investigate the influence of drying the ear canal by cleaning the focus of infection in the posterior tympanum in middle ear operations. METHOD: Retrospectively analyze 168 cases of middle ear operations, which were divided into two groups by whether the posterior tympanum was open or not in the operation process. Then comparing the drying ear rate. RESULT: The drying ear rate (DEC) were 81.7% (67/82) and 91.9% (79/86) in the posterior tympanum unopened and opened group, respectively. In the posterior tympanum unopened group, the DEC rate were 78.9% (30/38) and 84.1% (37/44) in 38 cases of chronic otitis media and mastoiditis with cholesteatoma and in 44 cases of chronic otitis media and mastoiditis with granulation tissue, respectively. In the posterior tympanum opened group, the DEC rate were 88.2% (37/42) and 94.7% (42/44) in 42 cases of chronic otitis media and mastoiditis with cholesteatoma and in 44 cases of chronic otitis media and mastoiditis with granulation tissue, respectively. In the posterior tympanum unopened group, the DEC rate were 81.7% (36/44) and 84.6% (34/38) in 44 cases of radical mastoidectomy and in 38 cases of tympanoplasty; compared with the posterior tympanum opened group, the DEC rate were 91.3% (42/46) and 92.5% (37/40) correspondingly. CONCLUSION: In the middle ear operation, open the posterior tympanum in convention can not only have profits to clear the insidious focus of infection, but also have profits to skeletonized to lower facial ridge to the utmost limits and make the drainage of the ear canal easy and smooth. At last, the rate of DEC was raised.

[Effects of invigorating the kidney and strengthening the bones capsule on osteoporosis in ovariectomized rats].

OBJECTIVE: To study the therapeutic effects of inrigorating the kidney and strengthening the bones capsule(IKSBC) on osteoporotic ovariectomized(OVX) rat model. METHODS: The concentrations of calcium, phosphorus and ALP in serum of ovariectomized rats were determined by clinical biochemical assay, and the right hind leg thighbones of ovariectomized rats were reserved for the preparation of bone specimens and were studied by bone histomorphometry. RESULTS: After treatment with IKSBC, the concentrations of calcium and phosphorus in ovariectomized rat serum were increased, the activity of ALP was decreased and the percentage of relative trabecular volume was increased significantly as compared with that before treatment(P < 0.05). CONCLUSION: IKSBC possesses some therapeutic effects on osteoporotic rat model.