[New discovery and short-term effect analysis of tensor tympani muscle tenotomy for Meniere's disease under otoscope].

Objective: To explore the feasibility and short-term effect of tensor tympani muscle Tenotomy in the treatment of Meniere's disease under otoscope. The possible pathogenesis was discussed and our views were put forward. Methods: The clinical data of 9 cases of Meniere's disease treated by otoscopic Tenotomy were analyzed retrospectively, including 2 males, 7 females, 5 right ones, 2 left ones and 2 bilateral ones. The average age was (56.33± 10.56) years, ranging from 38 to 75 years. We evaluated intraoperative findings and short-term postoperative efficacy, respectively evaluated postoperative aural fullness, tinnitus and hearing recovery, and evaluated postoperative vertigo attack in a short time. Results: Nine patients were completed the operation under general anaesthesia and otoscopy, and no serious complications occurred. We found new pathological changes in tympanic cavity in some cases during operation. There were rupture of round window membrane in 1 case, severe fibrous hyperplasia near the round window membrane and vestibular window and adhesion with ossicular chain in 1 case, fibrous cord and membranous hyperplasia near vestibular window and round window membrane in 1 case, fibrous hyperplasia and adhesion near the round window membrane in 2 cases, membranous hyperplasia and adhesion around vestibular window in 1 case. No fibrous hyperplasia was found in 3 cases in the tympanic cavity. The round window membrane can be exposed in 4 cases and failed in 5 cases. After 3 months of follow-up, we found that we found that 5/5 cases of aural fullness disappeared, 2/2 cases of earache disappeared, 3/8 cases of tinnitus improved, 5/8 cases presented with improvement and no aggravation, 3/3 cases of hearing allergy improved, 4/9 cases of hearing improved, and 5/9 cases showed no improvement or decrease. 9 patients were followed up for 3 months, of whom 8 patients had no vertigo, one patient suffered from vertigo twice within 3 months after operation, and the patient suffered from rupture of round window membrane. Conclusions: Endoscopic Tenotomy for Meniere's disease has obvious curative effect and quick recovery after operation. During the operation, we find that most of Meniere's patients have fibrous cord hyperplasia near the inner ear window membrane, which may be the pathological manifestation after repeated rupture and repair of the inner ear window membrane. The vertigo of Meniere's disease may be related to the destruction and repair of inner ear membrane structure caused by improper contraction or spasm of tympanic tensor muscle.

[Advances in immunotherapy of extranodal NK/T cell lymphoma].

Extranodal NK/T-cell lymphoma (ENKTCL) is a relatively rare group of highly aggressive non-Hodgkin's lymphoma (NHL). The disease has rapid clinical progress, high degree of malignancy and poor prognosis. Traditional chemoradiotherapy regimens have not shown good efficacy. In recent years, the immunotherapy of tumors has developed rapidly. At present, it has shown strong therapeutic activity in the treatment of various solid tumors such as non-small cell lung cancer, prostate cancer, melanoma and kidney cancer. Multiple tumor immunotherapy drugs have been approved by the US Food and Drug Administration (FDA) for clinical use. This article reviews recent novel immunotherapeutic regimens of ENKTCL, hoping to change the treatment modality of this malignant disease.

GDF11 does not improve the palmitate induced insulin resistance in C2C12.

OBJECTIVE: GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance. MATERIALS AND METHODS: High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro. The mRNA expression of GDF11, GLUT4, IRS-1 (insulin receptor substrate-1) and PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator 1) were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein level of GDF11 and PGC-1α were detected by Western blot. The glucose uptake was measured by 2NBDG uptake assay. RESULTS: In high fat diet induced obese mice, both serum level of GDF11 and the expression of GDF11 in skeletal muscle decreased. Similarly, the expression of GDF11 also reduced in palmitate-treated C2C12 myotubes. In vitro, the glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α significantly decreased after palmitate intervention, but GDF11 treatment did not reverse the reduction of glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α in C2C12 myotubes. CONCLUSIONS: We firstly confirmed that the expression of GDF11 decreased both in the skeletal muscle of obese mice and palmitate-treated myotubes, but supplementation GDF11 does not ameliorate the palmitate-induced insulin resistance in C2C12 myotubes.

Correlation between serum melatonin and aMT6S level for age-related macular degeneration patients.

OBJECTIVE: To analyze the levels of serum melatonin (MLT) and assay of 6-sulfatoxymelatonin (aMT6S) of age-related macular degeneration (AMD) patients and study their correlation with AMD risk factors. PATIENTS AND METHODS: 58 AMD cases were selected and 58 healthy cases of the same time period were selected according to 1:1 closest matching method. ELISA method was used to test serum MLT and aMT6S level. RESULTS: Levels of MLT and aMT6S in AMD group were lower than those in the control group, and differences were statistically significant (p < 0.05). Based on analysis of AMD subgroup, differences on gender had no statistical significance compared with AMD type. For cases with smoking, cardiovascular disease and corrected visual acuity lower than 0.1, MLT and aMT6S levels were reduced at 0.05). Through the regression analysis, we concluded that smoking history, cardiovascular disease history, best corrected visual acuity, MLT and aMT6S level were independent risk factors, among which MLT [OR = 3.624 (odds ratio: OR)] and aMT6S (OR = 3.201). CONCLUSIONS: MLT and aMT6S may be related to the incidence of AMD.

Association between peptidyl arginine deiminase 4 (PADI4)-104C/T polymorphism and rheumatoid arthritis: a meta-analysis in the Chinese population.

The correlation between the -104C/T polymorphism in the peptidyl arginine deiminase 4 (PADI4) gene and rheumatoid arthritis (RA) risk has been analyzed in several studies. However, the results are inconclusive and remain to be confirmed in several ethnic groups. The effect of the PADI4-104C/T polymorphism on RA risk in the Chinese population was evaluated in a meta-analysis. Studies with dates of publication up to July 2015 conforming to the inclusion criteria were retrieved from PubMed and Chinese databases. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (CIs). Ten studies, including 2119 RA cases and 1962 controls, that conformed to the study criteria were included in this analysis. The overall analysis indicated a significant association between the PADI4-104C/T polymorphism and RA risk in the Chinese population (T vs C: OR = 1.45, 95%CI = 1.18-1.78; TT vs CC: OR = 1.49, 95%CI = 1.24-1.80; TT vs CC+CT: OR = 1.28, 95%CI = 1.08-1.51; TT+CT vs CC: OR = 1.75, 95%CI = 1.30-2.37). Analysis of data stratified by the geographic area and source of controls revealed that the PADI4-104C/T polymorphism was significantly associated with RA risk in a North Chinese population. In conclusion, the results of this meta-analysis indicated that the PADI4-104C/T variants could influence the risk of RA in the Chinese population; further studies in other ethnic groups are required to draw definite conclusions.

Regulation of Eye Development by Protein Serine/Threonine Phosphatases-1 and -2A.

The protein serine/threonine phosphatases-1 and -2A are major cellular phosphatases, playing a fundamental role in organisms from prokaryotes to eukaryotes. They contribute to 90% dephosphorylation in eukaryote proteins. In the eye, both phosphatases are highly expressed and display important functions in regulating normal eye development. Moreover, they are implicated in pathogenesis through modulation of stress-induced apoptosis. Here we review the recent progresses on these aspects.

Consequences of additional use of contrast-enhanced (18)F-FDG PET/CT in target volume delineation and dose distribution for pancreatic cancer.

OBJECTIVE: To compare the differences between contrast-enhanced (CE) fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT and CECT in target volume delineation and radiotherapy (RT) dose distribution, and to evaluate the sparing of organs at risk (OARs) in the treatment plan of locally advanced pancreatic cancer (LAPC). METHODS: 21 consecutive patients with LAPC with histologically or cytologically confirmed adenocarcinoma underwent both non-CECT and (18)F-FDG scans; 11 of whom also underwent CECT scans. Intensity-modulated RT plans (prescribed dose, 54 Gy) were constructed to cover the corresponding gross tumour volume (GTV). The differences among GTVCT, GTVPET, GTVPET-CT and OARs in these different image sets as well as the uniformity of target dose were analysed. RESULTS: The mean non-CE GTVCT, GTVPET and GTVPET-CT were 76.9 ± 47.8, 47.0 ± 40.2 and 44.5 ± 34.7 cm(3) (mean ± standard deviation), respectively. The non-CE GTVPET-CT was significantly smaller than the non-CE GTVCT (p < 0.001). The CE GTVPET-CT was significantly smaller than the CE GTVCT (p = 0.033). For both the non-CE GTVCT and the CE GTVCT, the intestine V40 (the percentage of the intestine volume irradiated by 40 Gy), intestine V50, intestine Dmax (the mean maximum dose), cord Dmax, left kidney V30, right kidney V30, left kidney Dmean (the mean dose), right kidney Dmean and liver V30 were 5.90%, 2.52%, 5500 cGy, 2194 cGy, 3.40%, 0.68%, 747 cGy, 550 cGy and 5.37%, respectively. There are significant differences between the non-CE CT and the non-CE PET-CT in intestine Dmax (p = 0.023) and right kidney Dmean (p = 0.029). CONCLUSION: Co-registration of (18)F-FDG PET with CECT may improve the accuracy of GTV delineation in LAPC and might reduce the adverse effect of irradiation. ADVANCES IN KNOWLEDGE: Individual adaptation of RT based on functional CE (18)F-FDG PET/CT imaging is possible and highly promising in LAPC.

Benefits of postoperative radiotherapy in multimodality treatment of resected small-cell lung cancer with lymph node metastasis.

AIM: The purpose of this study is to evaluate the role of postoperative radiotherapy (PORT) in resected small-cell lung cancer (SCLC). METHODS: This study retrospectively analyzed 143 patients with completely resected SCLC in our institution between 1996 and 2011. The primary endpoint was overall survival (OS). The log-rank test and Cox regression model were used to evaluate the factors influencing local-regional recurrence (LRR) and OS. RESULTS: The median OS for the entire population was 34 months, and the 5-year OS rate was 34.6%. In multivariate analysis, age, surgical procedure, pathology stage, adjuvant chemotherapy and distant relapse were significant factors for survival. For the whole population, PORT had no effect on OS, with a median OS of 40 months in the PORT group versus 27 months in the non-PORT group (p = 0.260). However, in patients with N1 disease, the median OS were 40 months in the PORT group versus 14 months in the non-PORT group (p = 0.032). The corresponding OS in N2 patients were 35 months versus 17 months, respectively (p = 0.040). Similarly, PORT significantly reduced the LRR in patients with positive lymph node. For patients with N1 disease, the 3-year LRR rate was 0.0% in the PORT group versus 14.3% in the non-PORT group (p = 0.037). The corresponding LLR rate in N2 patients was 4.2% versus 56.6% (p < 0.001). CONCLUSION: PORT significantly reduced LRR and improved OS in patients with regional metastasis SCLC. We suggest supplementing PORT in the multimodality treatment of resected SCLC with lymph node metastasis.

Protein phosphatase-1 regulates Akt1 signal transduction pathway to control gene expression, cell survival and differentiation.

AKT pathway has a critical role in mediating signaling transductions for cell proliferation, differentiation and survival. Previous studies have shown that AKT activation is achieved through a series of phosphorylation steps: first, AKT is phosphorylated at Thr-450 by JNK kinases to prime its activation; then, phosphoinositide-dependent kinase 1 phosphorylates AKT at Thr-308 to expose the Ser-473 residue; and finally, AKT is phosphorylated at Ser-473 by several kinases (PKD2 and others) to achieve its full activation. For its inactivation, the PH-domain containing phosphatases dephosphorylate AKT at Ser-473, and protein serine/threonine phosphatase-2A (PP-2A) dephosphorylates it at Thr-308. However, it remains unknown regarding which phosphatase dephosphorylates AKT at Thr-450 during its inactivation. In this study, we present both in vitro and in vivo evidence to show that protein serine/threonine phosphatase-1 (PP-1) is a major phosphatase that directly dephosphorylates AKT to modulate its activation. First, purified PP-1 directly dephosphorylates AKT in vitro. Second, immunoprecipitation and immunocolocalization showed that PP-1 interacts with AKT. Third, stable knock down of PP-1alpha or PP-1beta but not PP-1gamma, PP-2Aalpha or PP-2Abeta by shRNA leads to enhanced phosphorylation of AKT at Thr-450. Finally, overexpression of PP-1alpha or PP-1beta but not PP-1gamma, PP-2Aalpha or PP-2Abeta results in attenuated phosphorylation of AKT at Thr-450. Moreover, our results also show that dephosphorylation of AKT by PP-1 significantly modulates its functions in regulating the expression of downstream genes, promoting cell survival and modulating differentiation. These results show that PP-1 acts as a major phosphatase to dephosphorylate AKT at Thr-450 and thus modulate its functions.

[Identification of fruits of Xanthium sibiricum Patr. and X. mongolicum Kitag].

The protein electrophorogram, tissue separation picture and complete powder characteristic picture of these two kinds of fruit of siberian cocklebur are made for the first time, and TLC chromatograms of different solvent extracts are also presented. All these present a scientific basis for crude drugs selling, breed identification and composition analysis of the fruit of siberian cocklebur.

Isolation of a mitomycin-resistant human lung adenocarcinoma cell subline to investigate the modulation by sodium butyrate of cell growth and drug resistance.

We developed a mitomycin C (MMC)-resistant human lung adenocarcinoma cell subline, SPC-A1/DM4, from cloned SPC-A1/D13 parent cells by 1 h exposures to escalating concentrations of the drug over 17 months. A 5.9-fold resistance to MMC and a 3.8-fold cross-resistance to cisplatin were present in resistant cells compared with parent cells. This phenotype was stable in the absence of drug exposure for at least 6 months. Sodium butyrate (NaBu), a widely used differentiating agent, was shown to inhibit cell proliferation in a dose-dependent manner, with the cytostatic concentration of 2 mM. This NaBu-induced growth inhibition was reversible. However, SPC-A1/DM4 cells, after recovery from the cytostasis induced by 2 days treatment with 2 mM NaBu, became 2-fold more sensitive to MMC than the cells not exposed to the agent. Meanwhile, the cisplatin response of these treated cells reached a level comparable to the parent cells. This modulation by NaBu of drug resistance could be retained for at least 1 month. Treatment with 2 mM NaBu for 2 days caused inhibition of DNA synthesis and accumulation of cells in the G1 and G2/M-phases of the cell cycle. Correlated with these were a marked increase of protein content in these cell subpopulations and an enhanced RNA synthesis. In addition, NaBu-treated cells acquired development of endoplasmic reticulum and accumulated lipid droplets. These morphological alterations were accompanied by a significant decrease in the ratio of nuclear to cytoplasmic areas. These findings suggest that NaBu is potentially useful in the treatment of drug-resistant non-small cell lung cancer. Information about the NaBu-induced phenotypic alterations may offer a clue to the understanding of its long-term effect on drug resistance.