Dihydroartemisinin inhibits HNSCC invasion and migration by controlling miR-195-5p expression.

Objectives: Dihydroartemisinin (DHA), an artemisinin derivative extracted from the traditional Chinese medicinal herb Artemisia annua, has the potential to suppress head and neck squamous cell carcinoma (HNSCC) progression. However, the mechanisms underlying these effects remain unclear. Therefore, we aimed to examine the mechanisms underlying the effects of DHA on tumor invasion and migration. Methods: Human HNSCC cell lines CAL-27 and FaDu were exposed to varying DHA concentrations (0, 5, 20, and 80 µM) for 24 h. Cell proliferation, invasion, and migration were assessed using CCK8, transwell, and wound-healing assays, respectively. Quantitative real-time PCR, western blotting, and immunofluorescence were used to assess the expression levels of the target genes and proteins. Results: DHA suppressed the invasion and migration of CAL-27 and FaDu cells. Additionally, miR-195-5p suppressed the invasion and migration of HNSCC cells. This study revealed significant differences in the expression of miR-195-5p and TENM2 between clinical samples and multiple public databases. DHA treatment and miR-195-5p overexpression significantly reduced TENM2 expression in HNSCC cells, which suggested that miR-195-5p overexpression enhanced the inhibitory effect of DHA on TENM2. Conclusions: This study provides the first evidence that DHA inhibits cell invasion and migration by regulating the miR-195-5p/TENM2 axis in HNSCC cells, suggesting it as a potentially effective treatment strategy for HNSCC.

Study on key parameters of buckling deformation instability and fracture of rock beams and asymmetric distribution law of stope stress.

The moving deformation of the strata and the redistribution of stope stress after mining show asymmetrical characteristics, which do not conform to the symmetrical structural characteristics of the original rock beam fracture. To further analyze the deformation of rock beams and the asymmetry law of stope pressure distribution after strata caving, the detailed process of instability and deformation of composite rock beams before failure was revealed through similar material simulation, theoretical analysis, and numerical simulation. Through similar simulation experiments, the structural characteristics of strata caving were observed. After excavation, the caving angle near the open-off cut side of the model is greater than that on the stop-mining line side. The maximum bending moment of the rock beam is located at the open-off cut side. The rock beam fracture is located on the partial open-off cut side in the middle of the rock beam. The rock beam on the open-off cut side is easy to shear slip and not easy to hinge. The rock beam in front of the advancing direction of the working face is easily hinged. Based on the structural characteristics of strata caving, considering the thickness of the composite rock beam, the two-hinged arch mechanical model for rock beam fracture is established. On this basis, the key parameters of rock beam instability and fracture such as limit load, additional horizontal stress, limit break distance, and break position are analyzed. Based on the deformation characteristics of two hinged arches, the caving structure and the asymmetric distribution mechanism of stress redistribution during the deformation of overburden in stope are explained. Finally, the deformation of rock beam and the asymmetry of stress distribution in stope are verified by numerical calculation. The results show that the concentrated stress value of the coal pillar at the open-off cut side is greater than that in front of the working face. There is a pressure relief area behind the working face, and the pressure relief area has a certain range. The range of stress concentration area, pressure relief area, and stress value tend to be stable, and only the range of the original rock stress zone expands when the working face is advanced to a certain distance. The asymmetric distribution of compaction stress in goaf is related to the buckling deformation of strata.

Highly Sensitive Qualitative and Quantitative Identification of Cashmere and Wool Based on Terahertz Electromagnetically Induced Transparent Metasurface Biosensor.

Cashmere and wool are both natural animal fibers used in the textile industry, but cashmere is of superior quality, is rarer, and more precious. It is therefore important to distinguish the two fibers accurately and effectively. However, challenges due to their similar appearance, morphology, and physical and chemical properties remain. Herein, a terahertz electromagnetic inductive transparency (EIT) metasurface biosensor is introduced for qualitative and quantitative identification of cashmere and wool. The periodic unit structure of the metasurface consists of four rotationally symmetric resonators and two cross-arranged metal secants to form toroidal dipoles and electric dipoles, respectively, so that its effective sensing area can be greatly improved by 1075% compared to the traditional dipole mode, and the sensitivity will be up to 342 GHz/RIU. The amplitude and frequency shift changes of the terahertz transmission spectra caused by the different refractive indices of cashmere/wool can achieve highly sensitive label-free qualitative and quantitative identification of both. The experimental results show that the terahertz metasurface biosensor can work at a concentration of 0.02 mg/mL. It provides a new way to achieve high sensitivity, precision, and trace detection of cashmere/wool, and would be a valuable application for the cashmere industry.

A novel cuproptosis-related gene signature of prognosis and immune microenvironment in head and neck squamous cell carcinoma cancer.

BACKGROUND: Cuproptosis is a novel form of cell death that is highly related to mitochondrial metabolism and mediated by protein lipoacetylation. This study systematically assessed the differential expression and genetic alterations of cuproptosis-related genes (CRGs) in head and neck squamous-cell carcinoma (HNSCC) and constructed CRG risk models to predict survival in patients with HNSCC. METHODS: We investigated the expression of 19 CRGs in HNSCC and noncancerous tissues, and the relationship between mutation load, immune infiltration, and clinical features was examined based on data from public databases. CRG risk models were constructed by univariate Cox analysis and lasso regression and validated by independent datasets for their accuracy in predicting survival outcomes in patients with HNSCC. The expression distribution of CRGs in HNSCC cells was further explored in the HNSCC single-cell sequencing dataset. RESULTS: NFE2L2, ATP7A, FDX1, LIAS, DLD, DLAT, PDHB, MTF1 and DBT were highly expressed in noncancerous samples, while GLS, CDKN2A and DLST were highly expressed in HNSCC samples (p < 0.05). Gene copy number variation frequency (CNV) revealed CDKN2A, FDX1 and DLAT copy number deletions and LIPT2 and NFE2L2 copy number increases. Ten CRGs were used to construct a risk model to predict overall survival (OS) in HNSCC, yielding reduced OS in the high-risk group compared to the low-risk group, training group (p = 9.733e - 05), and testing group (p = 0.040). The CRG risk model was significantly correlated with various immune cells, regulatory T cells (Tregs) and memory B cells were significantly negatively correlated (p = 0.027, p = 0.00084), and resting CD4 memory T cells was significantly positively correlated (p = 9e - 04). Most CRGs significantly affected the clinical characteristics of HNSCC. NFE2L2, SLC31A1, PDHA1, CDKN2A and DBT were highly expressed in epithelial cells of HNSCC, while SLC31A1, DBT and NFE2L2 were highly expressed in T cells, and SLC31A1 in B cells. In monocytes, NFE2L2, SLC31A1 and PDHA1 were highly expressed. CONCLUSION: The CRG risk model can be used as a potential prognostic factor for HNSCC patients and may provide new insights into cancer treatment from the perspective of copper metabolism.

Application of an Interpretable Machine Learning Model to Predict Lymph Node Metastasis in Patients with Laryngeal Carcinoma.

Objectives: A more accurate preoperative prediction of lymph node metastasis (LNM) plays a decisive role in the selection of treatment in patients with laryngeal carcinoma (LC). This study aimed to develop a machine learning (ML) prediction model for predicting LNM in patients with LC. Methods: We collected and retrospectively analysed 4887 LC patients with detailed demographical characteristics including age at diagnosis, race, sex, primary site, histology, number of tumours, T-stage, grade, and tumour size in the National Institutes of Health (NIH) Surveillance, Epidemiology, and End Results (SEER) database from 2005 to 2015. A correlation analysis of all variables was evaluated by the Pearson correlation. Independent risk factors for LC patients with LNM were identified by univariate and multivariate logistic regression analyses. Afterward, patients were randomly divided into training and test sets in a ratio of 8 to 2. On this basis, we established logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), and light gradient boosting machine (LightGBM) algorithm models based on ML. The area under the receiver operating characteristic curve (AUC) value, accuracy, precision, recall rate, F1-score, specificity, and Brier score was adopted to evaluate and compare the prediction performance of the models. Finally, the Shapley additive explanation (SHAP) method was used to interpret the association between each feature variable and target variables based on the best model. Results: Of the 4887 total LC patients, 3409 were without LNM (69.76%), and 1478 had LNM (30.24%). The result of the Pearson correlation showed that variables were weakly correlated with each other. The independent risk factors for LC patients with LNM were age at diagnosis, race, primary site, number of tumours, tumour size, grade, and T-stage. Among six models, XGBoost displayed a better performance for predicting LNM, with five performance metrics outperforming other models in the training set (AUC: 0.791 (95% CI: 0.776-0.806), accuracy: 0.739, recall rate: 0.638, F1-score: 0.663, and Brier score: 0.165), and similar results were observed in the test set. Moreover, the SHAP value of XGBoost was calculated, and the result showed that the three features, T-stage, primary site, and grade, had the greatest impact on predicting the outcomes. Conclusions: The XGBoost model performed better and can be applied to forecast the LNM of LC, offering a valuable and significant reference for clinicians in advanced decision-making.

Clinical and experimental study of a terahertz time-domain system for the determination of the pathological margins of laryngeal carcinoma.

OBJECTIVE: Laryngeal cancer is a common malignancy in otorhinolaryngological head and neck surgery, accounting for approximately one-third of all head and neck malignancies. Terahertz time-domain spectroscopy (THz-TDS) has recently been found to be useful for the detection of tumors. This study was conducted to investigate the application of THz-TDS in the diagnosis of pathological resection margins of laryngeal cancer. METHODS: Fresh laryngeal cancer tissues from 10 patients with laryngeal cancer were extracted, and after simultaneous HE staining and terahertz imaging, the tumor area, paracancerous area, and normal tissue area of each laryngeal cancer tissue sample were located under a microscope according to the pathological results of HE staining. RESULTS: The shape contours of the tumor region revealed by terahertz imaging maps and HE staining were similar. In the terahertz spectrum in the frequency range of 0.5-1.9 THz, both the absorption coefficient and refractive index values followed the order tumor > para cancer > normal tissue, with statistically significant differences (P < 0.01). When the terahertz frequency was 1.5 THz, the absorption coefficient of terahertz light waves by laryngeal cancer tissue and the percentage of nuclei showed an extremely high positive correlation (P < 0.01, r = 0.971). In the frequency ranges of 0.5-1.2 THz and 1.6-1.9 THz, the absorption coefficients of the highly differentiated group were higher than those of the moderately differentiated group. In the frequency range of 1.2-1.6 THz, the results were reversed, with statistically significant differences (P < 0.05). In the frequency range of 0.5-1.9 THz, the highly differentiated group had a higher refractive index than the moderately differentiated group, with a statistically significant difference (P < 0.05). CONCLUSIONS: THz-TDS can be used to determine the pathological margins of laryngeal cancer based on the absorption coefficient and refractive index, and the magnitudes of the absorption coefficient and refractive index are related to the percentage of nuclei. The degree of differentiation of laryngeal cancer tissue can be assessed by THz-TDS. The study shows that the terahertz time-domain system is promising for applications in the diagnosis of laryngeal cancer, especially for the more accurate identification of intraoperative margins.

The sensing mechanism of a flavone-based ESIPT fluorescent chemodosimeter for selective recognition towards fluoride: a theoretical.

The sensing mechanism of 3-hydroxyflavone-based (3-HF) fluorescent chemodosimeter 3-triisopropylsilylflavone (3-TPSF) for detecting fluoride (F-) has been theoretically investigated. The calculated Laplacian bond order confirms that the Si-O bond of 3-TPSF is the reaction site of F-. The free energy barrier of 18.33 kcal mol-1 indicates that F-triggered desilylation reaction can occur and then form the anionic state of 3-HF (3-HF-) with a fluorescence peak at 545 nm. 3-HF- captures H+ of the mixed aqueous medium to be transformed into 3-HF with an intramolecular hydrogen bond (O1-H⋯O2). The energy barrier of 1.86 kcal mol-1 in the S1 state obtained from the constructed potential energy curves confirms that the excited state intramolecular proton transfer (ESIPT) in 3-HF occurs to form a tautomer structure, which produces a long-wavelength emission of 549 nm. The fluorescence emitted from both 3-HF- and 3-HF agrees with the experimental value of 530 nm appearing after adding F-. Charge transfer analyses indicate that the extent of intramolecular charge transfer in 3-HF- is more intense than that of 3-TPSF, which induces a large Stokes shift of 180 nm. Therefore, the sensing mechanism is attributed to the combination of a large charge transfer feature and ESIPT that are caused by desilylation reaction. The significant fluorescence change makes 3-TPSF a chemodosimeter for detecting F-.

The influence of distance weight on the inverse distance weighted method for ore-grade estimation.

In order to study the influence of distance weight on ore-grade estimation, the inverse distance weighted (IDW) is used to estimate the Ni grade and MgO grade of serpentinite ore based on a three-dimensional ore body model and related block models. Manhattan distance, Euclidean distance, Chebyshev distance, and multiple forms of the Minkowski distance are used to calculate distance weight of IDW. Results show that using the Minkowski distance for the distance weight calculation is feasible. The law of the estimated results along with the distance weight is given. The study expands the distance weight calculation method in the IDW method, and a new method for improving estimation accuracy is given. Researchers can choose different weight calculation methods according to their needs. In this study, the estimated effect is best when the power of the Minkowski distance is 3 for a 10 m × 10 m × 10 m block model. For a 20 m × 20 m × 20 m block model, the estimated effect is best when the power of the Minkowski distance is 9.

Prognostic Value of Lymph Node Density in Patients With T3 and T4 Pyriform Sinus Carcinoma.

BACKGROUND/AIM: Lymph node density is a parameter used to more accurately predict tumor recurrence and patient survival. However, its association with surgical outcome in pyriform sinus carcinoma remains unclear. The purpose of this study was to assess the prognostic value of lymph node density in advanced pyriform sinus carcinoma. PATIENTS AND METHODS: A total of 87 patients with pyriform sinus carcinoma treated between 2008 and 2015 were enrolled. Then, 5-year overall survival, 5-year disease-specific survival, 5-year disease-free survival, and 5-year regional recurrence-free survival were utilized to assess the prognostic significance of lymph node density. RESULTS: With a median follow-up period of 31.8 months, 5-year overall survival, disease-specific survival, disease-free survival, and regional recurrence-free survival were 37.9%, 46.0%, 41.4%, and 54.0%, respectively. Univariate analysis revealed that lymph node density ≥ 0.093 was a significant predictor of poor 5-year overall survival (P = .005), disease-specific survival (P = .008), disease-free survival (P = .0013), and regional recurrence-free survival (P = .003). Furthermore, multivariate analysis demonstrated that lymph node density was negatively associated with adverse 5-year overall survival (hazard ratio = 1.62, 95% CI: 1.15-2.29, P = .006), disease-specific survival (hazard ratio = 1.86, 95% CI: 1.24-2.80, P = .003), disease-free survival (hazard ratio = 0.45, 95% CI: 0.24-0.85, P = .014), and regional recurrence-free survival (hazard ratio = 2.97, 95% CI: 1.43-6.17, P = .004). CONCLUSION: Taken together, these results reveal that lymph node density is a powerful prognostic factor for patients with T3 and T4 pyriform sinus carcinoma, and the median lymph node density cutoff values ≥ 0.093 are associated with a greater risk of recurrence and poorer survival.

Clinical experience of 23 cases of adenoid cystic carcinoma of the external auditory canal.

Adenoid cystic carcinoma (ACC) of the external auditory canal (EAC) is a rare tumor. The present study aimed to describe the clinical features and survival of patients with ACC of the EAC. The present retrospective study included 23 patients (mean age, 51.4±15.4 years; 12 males) diagnosed with ACC of the EAC between January 2010 and September 2017 at The First Affiliated Hospital of The Third Military Medical University (Chongqing, China). The median disease course was 24 months. The presenting features were earache in 16 patients, otorrhea in 7 patients, hearing loss in 5 patients, feeling of aural fullness in 2 patients and EAC mass in 4 patients. Tumor stage was T1 in 13 patients, T2 in 3 patients, T3 in 3 patients and T4 in 4 patients. Among patients with T1 tumors, 5 underwent en bloc external EAC resection; 3 underwent local EAC resection; 1 underwent en bloc EAC resection and superficial parotidectomy; 1 underwent subtotal temporal bone resection for postoperative recurrence; Among patients with T4 tumors, 1 underwent extended temporal bone resection, right parotidectomy, right resection of middle cranial fossa tumors and right resection of temporomandibular joint capsule. 1 underwent subtotal temporal bone resection. Among these 15 patients who underwent surgery, 2 received postoperative radiotherapy, 1 received postoperative chemotherapy, 5 received postoperative chemo-radiotherapy, and 7 did not receive postoperative chemo-radiotherapy. The 3- and 5-year cumulative survival rates of the 23 patients were 47.8% and 17.4%, respectively. Survival may have been improved in patients who received postoperative chemo-radiotherapy and early diagnosis may be the key to improving survival.

[Determination of pathological margin of hypopharyngeal cancer by terahertz time-domain spectroscopy system].

Objective:To investigate the accuracy of the terahertz system in differentiating hypopharyngeal cancer from normal tissue and its role in determining the pathological incised margin of hypopharyngeal cancer. Method:The transplantation model of hypopharyngeal cancer in 5-week-old male BALB/c nude mice were established by subcutaneous injection. The obtained transplanted tumor specimens were pathologically diagnosed to determine the extent of tumor tissue. Tumor tissue, normal tissue and paracellular tissue of transplantation tumor were scanned by terahertz time-domain spectroscopy. The differential spectral data were obtained through the detection of frozen tissue sections and paraffin tissue sections, respectively. The results were compared by t-test. Result:The tarahertz absorption coefficient of tumor tissues was higher than that of normal tissues, and the difference was statistically significant when the detection frequency was greater than 0.48 THz in frozen sections（P<0.05）. In the paraffin sections, the difference was statistically significant within the effective spectrum range of 0.2-1.6 THz（P<0.01）. The difference of refractive index between tumor tissue and normal tissue was significant in specimens treated in two ways（P<0.01）. The absorption coefficient of adjacent tissue felt between that of normal tissue and tumor tissue. Conclusion:Terahertz technology can distinguish tumor tissues and normal tissues accurately, and can detect the spectral changes in adjacent tissues sensitively. Therefore, terahertz technology may become another tool for the judgment of pathologic margin.

The effects of electron-withdrawing and electron-donating groups on the photophysical properties and ESIPT of salicylideneaniline.

The photophysical properties and excited state intramolecular proton transfer (ESIPT) of salicylideneaniline (1a) and its derivatives (1b-1e) with different substituents have been investigated using the DFT and TD-DFT methods. The calculated results indicate that the introduction of electron-withdrawing group CN weakens the intramolecular hydrogen bond (H···N). However, the introduction of electron-donating group N(CH3)2 strengthens it. When the CN and N(CH3)2 groups are introduced simultaneously, the intramolecular hydrogen bond (H···N) is weakened. In addition, swapping the CN and N(CH3)2 group positions can enhance the intramolecular hydrogen bond (H···N). Compared to 1a, the absorption and emission spectra of compounds 1b-1e are red-shifted. Frontier molecular orbital analyses prove that the more intense intramolecular charge transfer characters caused by CN and N(CH3)2 substituents is responsible for the red shift of spectra. Potential energy curves indicate that ESIPT in salicylideneaniline (1a) and the CN substituted derivative (1b) is a non-barrier process, while in the N(CH3)2 substituted derivative (1c) and the CN and N(CH3)2 co-substituted derivative (1d), ESIPT needs to overcome the energy barriers of 2.32 kcal/mol and 3.38 kcal/mol, respectively. Exchanging the positions of CN and N(CH3)2 groups (1e) makes the ESIPT into a barrier-free process. Therefore, the substitution and position of CN and N(CH3)2 groups can affect the ESIPT process and induce different photophysical properties.

Differential Gene Expression Patterns Between Apical and Basal Inner Hair Cells Revealed by RNA-Seq.

Tonotopic differences in the structure and physiological function, e.g., synapse number, membrane properties, Ca2+ channels, Ca2+ dependence of exocytosis and vesicle pool replenishment of inner hair cells (IHCs) along the longitudinal cochlear axis have recently been discovered, suggesting different gene expression patterns of IHCs. To determine whether IHCs present different gene expression patterns along the longitudinal cochlear axis, apical and basal IHCs were collected separately using the suction pipette technique from adult mouse cochleae for RNA-seq and genome-wide transcriptome analysis. We found 689 annotated genes showed more than 2-fold increase in expression. Interestingly, 93.4% of the differentially expressed genes (DEGs) was upregulated in apical IHCs. Although a subset of genes that related to IHC machinery and deafness were found to be differentially expressed, a gradient of gene expression was indeed detected in Ocm, Pvalb, Prkd1, Fbxo32, Nme2, and Sncg, which may play putative roles in the Ca2+ buffering and survival regulation. The expression of these genes was validated by real-time quantitative PCR (RT-qPCR) or immunostaining. We conclude that IHCs from different mouse cochlear longitudinal position have different gene expression profiles. Our data might serve as a valuable resource for exploring the molecular mechanisms underlying different biological properties as well as the survival regulation of IHCs.

[Combined inhibition of STAT3 and HIF-1α for enhancement of chemosensitivity in the model of human laryngeal squamous cacinoma in nude mice].

OBJECTIVE: To investigate the effects of combined inhibition of signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor-1α (HIF-1α) in the enhancement of chemosensitivity of the model of human laryngeal squamous cacinoma in nude mice. METHOD: Model nude mice were divided into six groups randomly: control group(A) , cisplatin group(B) , cisplatin and AG490 group(C) , cisplatin and HIF-1α⁻/⁻ group (D), cisplatin combined AG490 and HIF-1α⁻/⁻ group (E), HIF-1α⁻/⁻ group (F) (only in calculating tumor inhibition rate). 3mg/kg cisplatin was administered by peritoneal injection for 3 days. Then cisplatin and 10 mg/kg AG490 were administered every other day for 12 days. The expression of Ki67 and HIF-1α was detected by immunocytochemical method. Western blot was used to detect the expression of p-STAT3. RESULT: The expression of HIF-1α in group C and group D were lower than that in group B, and there were significant difference respectively (t1 = 2.782, t2 = 3.873, P < 0.05); The expression of HIF-1α in group E was lower than that in group C and group D respectively, and there were significant difference respectively (t1 = 6.140, t2 = 3.667, P < 0.01). The expression level of p-STAT3 in group C was markedly lower compared with that in group B, and there were significant difference between them (t = 17.840, P < 0.01); There were no difference between the expression level of p-STAT3 in group D and that in group B (t = 0.038, P > 0.05); The expression level of p-STAT3 in group E was significantly lower compared with that in group C and group D respectively (P < 0.01). Tumor inhibition rate of group E was higher than that in group B, group C , as well as group D respectively and there were significant difference respectively (t1 = 5.509, P < 0.01; t2 = 3.422, P < 0.05; t3 = 2.718, P < 0.05 ). Ki67 index of group E was lower than that in group B, group C as well as group D respectively and there were significant difference respectively(t1 = 8.307, P < 0.01; t2 = 3.736, P < 0.05; t3 = 4.524, P < 0.01). CONCLUSION: Combined inhibition of STAT3 and HIF-1α could enhance chemo-sensitivity in the model of human laryngeal squamous cacinoma in nude mice.

Dihydroartemisinin as a Putative STAT3 Inhibitor, Suppresses the Growth of Head and Neck Squamous Cell Carcinoma by Targeting Jak2/STAT3 Signaling.

Developing drugs that can effectively block STAT3 activation may serve as one of the most promising strategy for cancer treatment. Currently, there is no putative STAT3 inhibitor that can be safely and effectively used in clinic. In the present study, we investigated the potential of dihydroartemisinin (DHA) as a putative STAT3 inhibitor and its antitumor activities in head and neck squamous cell carcinoma (HNSCC). The inhibitory effects of DHA on STAT3 activation along with its underlying mechanisms were studied in HNSCC cells. The antitumor effects of DHA against HNSCC cells were explored both in vitro and in vivo. An investigation on cooperative effects of DHA with cisplatin in killing HNSCC cells was also implemented. DHA exhibited remarkable and specific inhibitory effects on STAT3 activation via selectively blocking Jak2/STAT3 signaling. Besides, DHA significantly inhibited HNSCC growth both in vitro and in vivo possibly through induction of apoptosis and attenuation of cell migration. DHA also synergized with cisplatin in tumor inhibition in HNSCC cells. Our findings demonstrate that DHA is a putative STAT3 inhibitor that may represent a new and effective drug for cancer treatment and therapeutic sensitization in HNSCC patients.

Interaction between TNFR1 and TNFR2 dominates the clinicopathologic features of human hypopharyneal carcinoma.

Although the expression of tumor necrosis factor receptors (TNFRs) has been associated with clinicopathologic features of some other cancers, their roles in hypopharyngeal squamous cell carcinoma (HPSCC) have not been documented. Forty-five HPSCC specimens were analyzed for the expression of TNFR1 and TNFR2 and its relationship with clinicopathologic factors. Interaction between the two receptors and its effects on TNF-α was investigated by neutralizing TNFR1 and upregulation of TNFR2. The results indicated that, in HPSCC specimens, the expression of TNFR1 but not TNFR2 is associated with clinical staging, T stage, cervical lymph node metastasis, and histologic grade in HPSCC. In Fadu cells, when conjugating with its receptors, TNF-α mediates proliferation effects, and neutralizing TNFR1 and/or upregulating TNFR2 evokes proliferation-inhibiting and apoptosis-inducing effects and potentiates cisplatin (DDP)-induced growth inhibition and apoptosis induction. In conclusion, interaction of TNFR1 with TNFR2 determines the biological characters of HPSCC, and TNFR1 may dominate this process. Moreover, interaction between the two receptors plays important roles in determining the fates of HPSCC cells and thus may serve as a therapeutic target for developing new therapeutic strategies for HPSCC.

Design and implementation of Metta, a metasearch engine for biomedical literature retrieval intended for systematic reviewers.

BACKGROUND: Individuals and groups who write systematic reviews and meta-analyses in evidence-based medicine regularly carry out literature searches across multiple search engines linked to different bibliographic databases, and thus have an urgent need for a suitable metasearch engine to save time spent on repeated searches and to remove duplicate publications from initial consideration. Unlike general users who generally carry out searches to find a few highly relevant (or highly recent) articles, systematic reviewers seek to obtain a comprehensive set of articles on a given topic, satisfying specific criteria. This creates special requirements and challenges for metasearch engine design and implementation. METHODS: We created a federated search tool that is connected to five databases: PubMed, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials. Retrieved bibliographic records were shown online; optionally, results could be de-duplicated and exported in both BibTex and XML format. RESULTS: The query interface was extensively modified in response to feedback from users within our team. Besides a general search track and one focused on human-related articles, we also added search tracks optimized to identify case reports and systematic reviews. Although users could modify preset search options, they were rarely if ever altered in practice. Up to several thousand retrieved records could be exported within a few minutes. De-duplication of records returned from multiple databases was carried out in a prioritized fashion that favored retaining citations returned from PubMed. CONCLUSIONS: Systematic reviewers are used to formulating complex queries using strategies and search tags that are specific for individual databases. Metta offers a different approach that may save substantial time but which requires modification of current search strategies and better indexing of randomized controlled trial articles. We envision Metta as one piece of a multi-tool pipeline that will assist systematic reviewers in retrieving, filtering and assessing publications. As such, Metta may find wide utility for anyone who is carrying out a comprehensive search of the biomedical literature.

[The role and mechanism of anticancer of dihydroartemisinin].

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells including cancers of cervix, pancreas, prostate, liver and neuroblastoma. Numerous studies in vivo and in vitro indicate that DHA possesses unique antitumor features and appears to be a promising chemotherapeutic agents. Here we systematically review the advances in research of anticancer of dihydroartemisinin, as well as summarize the mechanisms of its inducing apoptosis,delay cell-cycle, inhibitory cell proliferation and downregulate angiogenesis.