Obstructive sleep apnea-increased DEC1 regulates systemic inflammation and oxidative stress that promotes development of pulmonary arterial hypertension.

Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is a common risk factor for pulmonary arterial hypertension (PAH). As a hypoxia-induced transcription factor, differentially expressed in chondrocytes (DEC1) negatively regulates the transcription of peroxisome proliferative activated receptor-γ (PPARγ), a recognized protective factor of PAH. However, whether and how DEC1 is associated with PAH pathogenesis remains unclear. In the present study, we found that DEC1 was increased in lungs and pulmonary arterial smooth muscle cells (PASMCs) of rat models of OSA-associated PAH. Oxidative indicators and inflammatory cytokines were also elevated in the blood of the rats. Similarly, hypoxia-treated PASMCs displayed enhanced DEC1 expression and reduced PPARγ expression in vitro. Functionally, DEC1 overexpression exacerbated reactive oxygen species (ROS) production and the expression of pro-inflammatory cytokines (such as TNFα, IL-1ß, IL-6, and MCP-1) in PASMCs. Conversely, shRNA knockdown of Dec1 increased PPARγ expression but attenuated hypoxia-induced oxidative stress and inflammatory responses in PASMCs. Additionally, DEC1 overexpression promoted PASMC proliferation, which was drastically attenuated by a PPARγ agonist rosiglitazone. Collectively, these results suggest that hypoxia-induced DEC1 inhibits PPARγ, and that this is a predominant mechanism underpinning oxidative stress and inflammatory responses in PASMCs during PAH. DEC1 could be used as a potential target to treat PAH.

Metformin Inhibits Multiple Myeloma Serum-induced Endothelial Cell Thrombosis by Down-Regulating miR-532.

BACKGROUND: Thrombotic complications in multiple myeloma (MM) impairs the quality of life in patients. Metformin has a certain effect on anti-thrombosis, but its role and mechanism in MM-induced thrombosis are still uncovered. Therefore, this study evaluated the effect of metformin on MM-induced thrombosis. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to normal serum (15%), MM serum (15%), metformin (0.01 mmol/L), or MM serum, and metformin simultaneously. The expression of tissue factor (TF) in HUVECs was detected by flow cytometry and quantitative real-time polymerase chain reaction PCR (qRT-PCR). QRT-PCR was also used to determine the expressions of endothelial protein C receptor (EPCR) and miR-532. The generation of thrombin and activated protein C was measured by thrombin generation and protein C activation assays. EPCR, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway related protein expressions were detected by western blot. RESULTS: MM serum increased the expressions of TF and miR-532, induced thrombin generation, inhibited EPCR and protein C activation in HUVECs. And metformin could reverse the effects of MM serum on the expressions of TF, EPCR and miR-532, thrombin generation, protein C activation in HUVECs. However, miR-532 mimic reversed the effects of metformin and promoted the levels of thrombosis-related indicators in HUVECs. Moreover, metformin activated the ERK 1/2, p38 MAPK, and NF-κB pathways but miR-532 mimic suppressed the pathway activation. CONCLUSIONS: Metformin played an inhibitory effect on MM serum-induced HUVEC thrombosis, suggesting that metformin could serve as a novel antithrombotic approach for MM patients.

Management of isolated coronal shear fractures of the humeral capitellum with Herbert screw fixation through anterolateral approach.

BACKGROUND: Due to the intraarticular and complex nature of the coronal shear fracture of the humeral capitellum and its rarity, it has been difficult to formulate a universally accepted method of surgical management. The purpose of this study is to retrospectively evaluate the clinical outcomes of 15 patients with isolated coronal shear fractures of the capitellum treated by Herbert screw fixation through anterolateral approach, and to address the safety and tips for this surgical procedure. METHODS: This retrospective study included 15 isolated coronal shear fractures of the capitellum without posterior involvement, which were classified according to the Dubberley classification as 11 type 1A fractures and 4 type 3A fractures. All fractures were treated with Herbert screws fixation via the anterolateral approach. Clinical and radiographic evaluation was performed regularly, with a mean follow-up of 29 months. RESULTS: The mean operative time was 81 min. There were no wound healing problems or infection. One incomplete posterior interosseous nerve injury occurred, which recovered soon without residual compromise. All fractures healed well. At the final follow-up, the average range of motion was 134°in flexion-extension and 172°in supination-pronation. There was no significant difference between the affected and the unaffected elbows with regard to motion in flexion-extension or flexion-extension. The average Mayo Elbow Performance Index Score was 93 with 11 excellent and 4 good. No evidence of avascular necrosis, posttraumatic osteoarthritis, or heterotrophic ossification was found. CONCLUSION: Open reduction and internal fixation using Herbert screws through a anterolateral approach is a reliable and effective treatment for coronal shear fractures of capitellum, and able to achieve stable fixation and restoration of a functional range of motion.

Achaete-scute complex homologue-1 promotes development of laryngocarcinoma via facilitating the epithelial-mesenchymal transformation.

Laryngeal cancer is one of the most common fatal cancers among head and neck carcinomas, whose mechanism, however, remains unclear. The proneural basic-helix-loop-helix protein achaete-scute complex homologue-1, a member of the basic helix-loop-helix family, plays a very important role in many cancers. This study aims to explore the clinical value and mechanism of achaete-scute complex homologue-1 in laryngeal cancer. Methods including Cell Counting Kit-8, flow cytometry, Transwell invasion assays, and scratch assay were adopted to further explore the bio-function of achaete-scute complex homologue-1, whose expression was examined in fresh and paraffin chip of laryngeal carcinoma tissues by means of western blot and immunohistochemistry, after the interference of achaete-scute complex homologue-1; achaete-scute complex homologue-1, an overexpression in laryngeal carcinoma whose carcinogenicity potential was confirmed via western blot, was correlative with T classification (p = 0.002), histological differentiation (p = 0.000), lymph node metastasis (p = 0.000), and poor survival (p = 0.000). Multivariate analysis shows that achaete-scute complex homologue-1 overexpression is an independent prognostic factor unfavorable to laryngeal carcinoma patients (p = 0.000). Moreover, knocking down achaete-scute complex homologue-1 expression could significantly suppress the proliferation, migration, and invasion of laryngeal carcinoma cell in vitro and disorder epithelial-mesenchymal transformation-associated protein expression. Achaete-scute complex homologue-1 plays an important role in the genesis and progression of laryngeal carcinoma and may act as a potential biomarker for therapeutic target and prognostic prediction.

Bone Age and Serum Osteocalcin Levels in Children With Obstructive Sleep Apnea Hypopnea Syndrome Before and After Adenotonsillectomy.

Our aim was to study the changes in bone age and serum osteocalcin levels before and after adenotonsillectomy (AT) in children with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 58 OSAHS children (37 males and 21 females) with the mean age of 6.68 ± 1.11 years were enrolled and assessed by x-ray-based bone age estimation and enzyme-linked immunosorbent assay-based measurement of serum osteocalcin levels, before surgery and 6 months after AT. SPSS 19.0 software was used for statistical analysis. Our results revealed that bone age and serum osteocalcin levels in OSAHS patients were significantly lower than normal controls before AT (P < 0.05). Within 6 months after surgery, the bone age and the serum osteocalcin levels were significantly elevated in OSAHS patients (P < 0.05), compared with those before surgery. Serum osteocalcin levels and bone age are negatively correlated with apnea-hypopnea index, oxygen desaturation index, the percentage of the total recorded time spent below 90% oxygen saturation, and Epworth sleepiness scale scores (all P < 0.05). Our findings suggested that bone age and serum osteocalcin levels may be correlated with the development of OSAHS in children. AT may improve bone age and serum osteocalcin levels in OSAHS children.

[The modified Valsalva maneuver in hypopharynx CT scan].

Objective:To analyze the significance and factors influencing of CT scan under the modified Valsalva maneuver. Methods:Clinical data of 52 patients with hypopharyngeal carcinoma diagnosed from August 2021 to December 2022 were collected, all patients had calm breathing CT scan and modified Valsalva maneuver CT scan. Compare the exposure effect of the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall, and glottis with each CT scanning method. The effects of age, neck circumference, neck length, BMI, tumor site, and T stage on the exposure effect were analyzed. Results:In 52 patients, 50 patients（96.15%） completed CT scan at once time. The exposure effect of the CT scan under modified Valsalva maneuver in the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall was significantly better than CT scan under calm breathing（Z=-4.002, -8.026, -8.349, -7.781, -8.608, all P<0.01）, while CT scan under modified Valsalva maneuver was significantly worse in glottis than CT scan under calm breathing（Z=-3.625, P<0.01）. In the modified Valsalva CT scan, age had no obvious effect on the exposure effect. The exposure effect was better with long neck length, smaller neck circumference, smaller BMI and smaller T stage. The exposure of postcricoid carcinoma was better than pyriform sinus carcinoma and posterior hypopharyngeal wall carcinoma. But differences were not all statistically significant. Conclusion:The anatomical structure of the hypopharynx was clearly under CT scan with modified Valsalva maneuver, which clinical application is simple, but the effect of glottis was worse. The influence of age, neck circumference, neck length, BMI, and tumor T stage on the exposure effect still needs further investigation.

NGR-modified PEG-PLGA micelles containing Shikonin enhance targeting of dendritic cells for therapy of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a disease in the nasal mucosa related with Th2 lymphocyte inflammatory action. Dendritic cells (DCs) have been proved that they played a significant role in the development and maintenance of AR. However, there is still a lack of specific therapies for DCs in clinical practice. Shikonin (SHI) is a natural naphthoquinone compound isolated from the Chinese herb Radix Arnebiae. It is reported that SHI can interference the phenotype and function of dendritic cells, so we speculate that SHI may be an effective drug for the treatment of AR. However, the clinical usage of SHI has been limited by the bioactive properties of poor solubility, short retention time and low bioavailability. Therefore, in order to better exert the anti-inflammatory effect of SHI, an efficient SHI delivery system is urgently needed. METHODS: We prepared and characterized SHI-PM and NGR-SHI-PM with the thin-film hydration method. We used retrodialysis method to explore the release behavior. We took immunofluorescence to investigate the expression of CD13 in vitro. Then we tested BM-DCs mature cell detection by flow cytometry. An allergic rhinosinusitis murine model, hematoxylin and eosin stain and flow cytometry were established to test the efficiency of anti-inflammation in vivo. At last, western blot analysis and plasmid construction and transfection assay were taken to reveal the molecular mechanisms. RESULTS: In the present study, we revealed that NGR-modifified could strengthen the intracellular uptake of PM (p < 0.001) and CD13 was high expressed on mature BM-DCs (p < 0.001). NGR-modified could enhance the inhibition of SHI in vitro (p < 0.05). NGR-modifified could increase the distribution of PM in vivo by DiI fluorescently (p < 0.01). NGR-modified could enhance SHI anti-allergic activity in OVA-sensitized mice and enhance the inhibition of SHI on DC maturation in lymph node (p < 0.001). Our findings also suggest that SHI may have the inhibitory effect on AR through NF-κB pathway by targeting PARP. CONCLUSIONS: In summary, we have shown that NGR-PM-SHI could be a novel strategy for targeted treating allergic rhinitis through the NF-κB pathway by targeting PARP.

CT Texture Analysis for Preoperative Identification of Lymphoma from Other Types of Primary Small Bowel Malignancies.

OBJECTIVES: To explore the application of computed tomography (CT) texture analysis in differentiating lymphomas from other malignancies of the small bowel. METHODS: Arterial and venous CT images of 87 patients with small bowel malignancies were retrospectively analyzed. The subjective radiological features were evaluated by the two radiologists with a consensus agreement. The region of interest (ROI) was manually delineated along the edge of the lesion on the largest slice, and a total of 402 quantified features were extracted automatically from AK software. The inter- and intrareader reproducibility was evaluated to select highly reproductive features. The univariate analysis and minimum redundancy maximum relevance (mRMR) algorithm were applied to select the feature subsets with high correlation and low redundancy. The multivariate logistic regression analysis based on texture features and radiological features was employed to construct predictive models for identification of small bowel lymphoma. The diagnostic performance of multivariate models was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The clinical data (age, melena, and abdominal pain) and radiological features (location, shape, margin, dilated lumen, intussusception, enhancement level, adjacent peritoneum, and locoregional lymph node) differed significantly between the nonlymphoma group and lymphoma group (p < 0.05). The areas under the ROC curve of the clinical model, arterial texture model, and venous texture model were 0.93, 0.92, and 0.87, respectively. CONCLUSION: The arterial texture model showed a great diagnostic value and fitted performance in preoperatively discriminating lymphoma from nonlymphoma of the small bowel.

Endothelial Dec1-PPARγ Axis Impairs Proliferation and Apoptosis Homeostasis Under Hypoxia in Pulmonary Arterial Hypertension.

Background: The hypoxia-induced pro-proliferative and anti-apoptotic characteristics of pulmonary arterial endothelial cells (PAECs) play critical roles in pulmonary vascular remodeling and contribute to hypoxic pulmonary arterial hypertension (PAH) pathogenesis. However, the mechanism underlying this hypoxic disease has not been fully elucidated. Methods: Bioinformatics was adopted to screen out the key hypoxia-related genes in PAH. Gain- and loss-function assays were then performed to test the identified hypoxic pathways in vitro. Human PAECs were cultured under hypoxic (3% O2) or normoxic (21% O2) conditions. Hypoxia-induced changes in apoptosis and proliferation were determined by flow cytometry and Ki-67 immunofluorescence staining, respectively. Survival of the hypoxic cells was estimated by cell counting kit-8 assay. Expression alterations of the target hypoxia-related genes, cell cycle regulators, and apoptosis factors were investigated by Western blot. Results: According to the Gene Expression Omnibus dataset (GSE84538), differentiated embryo chondrocyte expressed gene 1-peroxisome proliferative-activated receptor-γ (Dec1-PPARγ) axis was defined as a key hypoxia-related signaling in PAH. A negative correlation was observed between Dec1 and PPARγ expression in patients with hypoxic PAH. In vitro observations revealed an increased proliferation and a decreased apoptosis in PAECs under hypoxia. Furthermore, hypoxic PAECs exhibited remarkable upregulation of Dec1 and downregulation of PPARγ. Dec1 was confirmed to be crucial for the imbalance of proliferation and apoptosis in hypoxic PAECs. Furthermore, the pro-surviving effect of hypoxic Dec1 was mediated through PPARγ inhibition. Conclusion: For the first time, Dec1-PPARγ axis was identified as a key determinant hypoxia-modifying signaling that is necessary for the imbalance between proliferation and apoptosis of PAECs. These novel endothelial signal transduction events may offer new diagnostic and therapeutic options for patients with hypoxic PAH.

The Antitumoral Effect of Paris Saponin II on Head and Neck Squamous Cell Carcinomas Mediated via the Nitric Oxide Metabolic Pathway.

Paris saponin has shown great therapeutic value in cancer therapy. We used isolated Paris saponin II (PSII), an active component of Paris saponin, and demonstrated its antitumor effect on human head and neck squamous cell carcinoma cell lines. Additionally, we investigated its mechanisms of action in vivo by establishing a xenograft mouse model. The results showed that PSII had presented strong anticancer effects on both hypopharyngeal malignant tumor cell lines (FaDu) and laryngeal carcinoma cell lines (Tu212 and Tu686). In addition, we successfully isolated and cultured the head and neck squamous stem cells and the primary fibroblasts to perform metabonomics studies. The results showed that RPII remarkably decreased energy metabolism, and type III nitric oxide synthase 3 (NOS3) may be a target to block tumor growth. Furthermore, we found that PSII inhibited HNSCC proliferation and metastasis by inhibiting the nitric oxide metabolic pathway. Overall, these results demonstrated that PSII is a potent anticancer agent, and the metabonomics analysis is a valuable tool to investigate and establish the antitumor effects of traditional Chinese medicines.

Combined treatment with acetazolamide and cisplatin enhances the chemosensitivity of human head and neck squamous cell carcinoma TU868 cells.

AIMS: To investigate whether combination of acetazolamide and cisplatin can enhance the chemosensitivity of human head and neck squamous cell carcinoma (HNSCC) cell line TU868. METHODS: MTT assay was performed to determine the effect of acetazolamide, cisplatin and their combination on the proliferation of TU868 cells. Then the effect of these 2 drugs on the expression of proliferation-related and apoptosis-related proteins was detected by Western blot. Moreover, the effect of acetazolamide and cisplatin on the expression of aquaporin-1 was detected by RT-qPCR. Loss-of-function assays was performed to assess whether the effect of acetazolamide and cisplatin on TU868 cells was mediated by aquaporin-1. The effect of acetazolamide and cisplatin on tumor cell growth was confirmed in mice by testing the tumor growth size. RESULTS: Acetazolamide and cisplatin treatment displayed synergistic effects on the inhibition of TU868 cell growth compared with the drugs used alone. Moreover, the acetazolamide/cisplatin combination could decrease the level of PCNA but increase the level of p53; decrease the ratio of Bcl-2/Bax and increase the expression of caspase-3 compared with the single drug treated group. Moreover, we found that the combination also significantly inhibits aquaporin-1 expression. Loss-of-function assays suggested that the anti-tumor effect of these 2 drugs was achieved via affecting aquaporin-1. Consistent with the in vitro assays, combined treatment with acetazolamide and cisplatin significantly inhibits the tumor growth in mice compared with the single drug treated group. CONCLUSION: These results demonstrated that combined treatment with acetazolamide and cisplatin could synergistically inhibit the malignant development of HNSCC cells.

Long noncoding RNA DLEU2 predicts a poor prognosis and enhances malignant properties in laryngeal squamous cell carcinoma through the miR-30c-5p/PIK3CD/Akt axis.

Long noncoding RNAs (lncRNAs) have been identified as potential prognostic tools and therapeutic biomarkers for a variety of human cancers. However, the functional roles and underlying mechanisms of key lncRNAs affecting laryngeal squamous cell carcinomas (LSCCs) are largely unknown. Here, we adopted a novel subpathway strategy based on the lncRNA-mRNA profiles from the Cancer Genome Atlas (TCGA) database and identified the lncRNA deleted in lymphocytic leukemia 2 (DLEU2) as an oncogene in the pathogenesis of LSCCs. We found that DLEU2 was significantly upregulated and predicted poor clinical outcomes in LSCC patients. In addition, ectopic overexpression of DLEU2 promoted the proliferation and migration of LSCC cells both in vivo and in vitro. Mechanistically, DLEU2 served as a competing endogenous RNA to regulate PIK3CD expression by sponging miR-30c-5p and subsequently activated the Akt signaling pathway. As a target gene of DLEU2, PIK3CD was also upregulated and could predict a poor prognosis in LSCC patients. In conclusion, we found that the novel LSCC-related gene DLEU2 enhances the malignant properties of LSCCs via the miR-30c-5p/PIK3CD/Akt axis. DLEU2 and its targeted miR-30c-5p/PIK3CD/Akt axis may represent valuable prognostic biomarkers and therapeutic targets for LSCCs.

A real-time road detection method based on reorganized lidar data.

Road Detection is a basic task in automated driving field, in which 3D lidar data is commonly used recently. In this paper, we propose to rearrange 3D lidar data into a new organized form to construct direct spatial relationship among point cloud, and put forward new features for real-time road detection tasks. Our model works based on two prerequisites: (1) Road regions are always flatter than non-road regions. (2) Light travels in straight lines in a uniform medium. Based on prerequisite 1, we put forward difference-between-lines feature, while ScanID density and obstacle radial map are generated based on prerequisite 2. According to our method, we construct an array of structures to store and reorganize 3D input firstly. Then, two novel features, difference-between-lines and ScanID density, are extracted, based on which we construct a consistency map and an obstacle map in Bird Eye View (BEV). Finally, the road region is extracted by fusing these two maps and refinement is used to polish up our outcome. We have carried out experiments on the public KITTI-Road benchmark, achieving one of the best performances among the lidar-based road detection methods. To further prove the efficiency of our method on unstructured road, the visual outcomes in rural areas are also proposed.

Comparison of lateral approach versus anterolateral approach with Herbert screw fixation for isolated coronal shear fractures of humeral capitellum.

BACKGROUND: For coronal shear fractures of humeral capitellum, the lateral approach is the most commonly used surgical approach. However, exposure range of the anterior aspect of the distal humerus is inadequate. The anterolateral approach has also been adopted to overcome this disadvantage. However, this approach seems anatomically complex due to the risk of iatrogenic injury to the radial nerve. So far, the optimal approach for the treatment of capitellar shear fractures remains inconclusive. The purpose of this study is to prospectively review and compare the early clinical and radiographic outcomes of treated with open reduction and Herbert screw internal fixation through the lateral approach or the anterolateral approach. METHODS: Twenty-six patients with isolated capitellar shear fractures were enrolled from January 2013 to December 2017, and randomly assigned to lateral approach group or anterolateral approach group. All the fractures were treated with open reduction and Herbert screw internal fixation through lateral approach or anterolateral approach. Operation time, wound healing complication, elbow joint function, and radiographic evidence were evaluated and compared between two groups. RESULTS: The operation via the anterolateral approach took significantly shorter time than via lateral approach (p < 0.05). There were no wound healing problems and infection for both groups. One patient from anterolateral approach group sustained incomplete posterior interosseous nerve palsy, which recovered completely in 4 weeks without residual compromise. All fractures healed well in their normal anatomic position as seen on radiographs. At the final follow-up, no significant difference was found between two groups with respect to the ROM in supination-pronation, ROM in pronation-supination, loss of flexion-extension motion, or loss of pronation-supination motion (p > 0.05). There is no significant difference with respect to MEPI score of elbow joint between two groups (p > 0.05). CONCLUSION: Based on our findings, both lateral approach and anterolateral approach with Herbert screw internal fixation are suitable for coronal shear fractures of capitellum with satisfactory early outcomes. Compared with the lateral approach, the anterolateral approach made the surgical procedure easier and time saving in current series. When the medial aspect of the trochlea is involved for capitellar coronal fractures, the anterolateral lateral approach should be preferred.

Overexpression of cFLIP in head and neck squamous cell carcinoma and its clinicopathologic correlations.

PURPOSE: The aim of this study was to determine the expression of cellular FLICE-like inhibitory protein (cFLIP) in head and neck squamous cell carcinoma (HNSCC) and revealed its possible correlation to Fas protein and tumour clinical parameters. METHODS: The expression of cFLIP was analysed in 58 HNSCC samples and 30 morphologically normal tissues adjacent to the carcinomas using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Furthermore, its possible correlation to the expression of Fas protein and tumour clinicopathologic parameters were discussed. RESULTS: Cellular FLICE-like inhibitory protein was demonstrated to be up regulated in most HNSCC than in normal tissues by immunohistochemistry (p<0.01). Although the mRNA levels of both isoforms of cFLIP, long form (cFLIP(L)) and short form (cFLIP(S)), in HNSCC were higher than those in normal tissues (p<0.01), only cFLIP(L) protein could be detected by western blot. Furthermore, the expression of cFLIP(L) protein was significantly associated with tumour clinical stage (p<0.01) and lymph node metastasis (p=0.01). Since all of the tumours with Fas immunostaining also express cFLIP protein, there was no significant correlation between them (p>0.05). CONCLUSIONS: Overexpression of cFLIP(L) is a frequent event in HNSCC and HNSCC cells in vivo may need it to evade apoptosis mediated by Fas or other receptors, which might contribute to tumour development and progression.

Histiocytic sarcoma of the neck: A case report.

Histiocytic sarcoma (HS) is a term used to describe malignant hyperplasia of cells exhibiting morphological and immunophenotypical characteristics similar to those of mature cells, with expression of one or more tissue cell markers, excluding acute monocytic leukemia and primitive monocytic sarcoma. We herein describe a case of histiocytic sarcoma of the neck supported by histopathological and immunohistological evidence. A 53-year-old female patient of Chinese descent presented with a rapidly enlarging right neck mass. Imaging studies revealed multiple right cervical lymphadenectases with right jugular vein involvement. The tumor was composed of diffusely distributed large non-cohesive tumor cells, round or oval and focally spindle-shaped. The tumor cells were immunopositive for macrophage-associated antigen CD68 and lysosomes, mostly consistent with a diagnosis of HS. HS is very prone to systemic metastasis; therefore, early diagnosis and timely treatment are crucial.

Effects of the Akt inhibitor Src-homology 5 on proliferation and apoptosis of the laryngeal squamous cell carcinoma.

OBJECTIVE: The aim of this study was to investigate the effect of the Akt inhibitor Src-homology 5 (SH-5) on the proliferation and apoptosis of laryngeal squamous cell carcinoma cells (LSCC; Hep-2 cells) and to elucidate the possible mechanisms of such effects. MATERIALS AND METHODS: Hep-2 cells were treated with different concentrations of the Akt inhibitor SH-5. The inhibitory effect of SH-5 on cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, whereas apoptosis was detected by flow cytometric based on Annexin V/propidium iodide (PI) staining. In addition, the expression level of Akt protein was evaluated by Western blot analysis. RESULTS: MTT assay results revealed that SH-5 inhibited the proliferation of Hep-2 cells, with its greatest effect being observed at 2 µM. Apoptosis of Hep-2 cells increased following treatment with SH-5. Treatment of Hep-2 cells with SH-5 decreased the expression of Akt, and this effect was statistically significantly when compared with that in controls (P < 0.05). CONCLUSION: SH-5 inhibited proliferation and induced apoptosis in the LSCC cell line Hep-2. These effects may be caused by inhibition of the phosphoinositide 3-kinase-Akt signaling pathway. We believe that our data will provide useful insights into LSCC target treatment and future researchn.

MCM7 expression is correlated with histological subtypes of lung adenocarcinoma and predictive of poor prognosis.

Emerging evidence has implicated that the abnormal expression of MCM3 and MCM7 contributes to tumor formation and progression. However, MCM3 and MCM7 protein expression in different subtypes of lung adenocarcinoma have not yet been reported. In the present study, we detected MCM7 and MCM3 protein level in five subtypes of lung adenocarcinoma by immunohistochemistry. The five subtypes can be divided into 3 grades-grade 1: lepidic adenocarcinoma, grade 2: acinar or papillary adenocarcinoma and grade 3: solid or micropapillary adenocarcinoma. The immunostaining showed that MCM7 level was lowest in the grade 1 subtype and highest in the grade 3 subtypes. The statistical analysis proved that MCM7 expression increased step wisely with the ascending of tumor grades. However, there is no significant relationship between MCM3 expression and tumor grades. In addition, we investigated the association of MCM7 and MCM3 expression with clinicopathological characteristics. The results showed that tumors with lymph node metastasis had higher MCM7 level than those without lymph node metastasis statistically (P<0.0001). MCM3 expression has no significant relationship with clinicopathological characteristics. In conclusion, our results suggested that MCM7 may be a useful biomarker for the pathological diagnosis of subtypes of lung adenocarcinoma and it also may be a potential prognostic marker for lung adenocarcinoma.

Salicylate-induced changes in immediate-early genes in the hippocampal CA1 area.

Studies have suggested that salicylate affects neuronal function via interactions with specific membrane channels/receptors. However, the effect of salicylate on activity and synaptic morphology of the hippocampal Cornu Ammonis (CA) 1 area remains to be elucidated. The activation of immediate-early genes (IEGs) was reported to correlate with neuronal activity, in particular activity-regulated cytoskeleton-associated protein and early growth response gene 1. The aim of the present study was to evaluate the expression of these IEGs, as well that of N-methyl D-aspartate (NMDA) receptor subunit 2B in rats following acute and chronic salicylate treatment. Protein and messenger RNA levels of all three genes were increased in rats following chronic administration of salicylate (300 mg/kg for 10 days), returning to baseline levels 14 days post-cessation of treatment. The transient upregulation of gene expression following treatment was accompanied by ultrastructural alterations in hippocampal CA1 area synapses. An increase in synaptic interface curvature was observed as well as an increased number of presynaptic vesicles; in addition, postsynaptic densities thickened and lengthened. In conclusion, the results of the present study indicated that chronic exposure to salicylate may lead to structural alteration of hippocampal CA1 neurons, and it was suggested that this process occurs through induced expression of IEGs via NMDA receptor activation.