Novel pretreatment nomograms based on pan-immune-inflammation value for predicting clinical outcome in patients with head and neck squamous cell carcinoma.

Background: The prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients. Methods: A total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms. Results: Patients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25-7.72; p<0.0001) and overall survival (OS) (HR, 5.23; 95% CI, 3.34-8.18; p<0.0001) compared to patients with lower PIV (<123.3) in the development cohort. Predictors of Model A included age, TNM stage, neutrophil-to-lymphocyte ratio (NLR), and PIV, and that of Model B included TNM stage, lymphocyte-to-monocyte ratio (LMR), and PIV. In comparison with TNM stage alone, the two nomograms demonstrated good calibration and discrimination and showed satisfactory clinical utility in internal validation. The generality testing results showed that higher PIV was also associated with worse survival outcomes in the RT/CRT cohort and the possibility that the two nomograms may have a universal applicability for patients with different treatments. Conclusions: The nomograms based on PIV, a simple but useful indicator, can provide prognosis prediction of individual HNSCC patients after radical surgery and may be broadly applicated for patients after RT/CRT alone.

[Resveratrol increases sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia].

OBJECTIVE: To explore the sensitization effects of resveratrol on CNE2 nasopharyngeal carcinoma cell line with hypoxia-induced chemotherapy resistance and the potential mechanism. METHODS: Human CNE2 nasopharyngeal carcinoma cell line was cultured under hypoxic conditions (37 degrees centigrade, 5% CO(2), 2% O(2)) in vitro. The cultured cells were treated with different concentrations of resveratrol for 48 h. Reversal fold (RF) of reseratrol to chemotherapeutic drugs in CNE2 cells was measured by methyl thiazolyl tetrazolium (MTT) assay. Apoptotic rate of CNE2 cells was observed by flow cytometry. Reverse transcription-polymerase chain reaction (RT-PCR) method and Western blotting were used to investigate the expressions of multidrug resistance gene 1 (mdr1), multidrug resistance-associated protein 1 (MRP1) and hypoxia inducible factor 1alpha (HIF-1alpha) in CNE2 cells. RESULTS: Resveratrol combined with chemotherapeutics produced a synergistic effect. The RF of 200 micromol/L resveratrol to paclitaxel was 2.58. Combined with paclitaxel, 25, 50, 100 and 200 micromol/L of resveratrol increased the apoptotic rate of CNE2 cells from (22.14+/-1.09)% to (23.24+/-1.37)%, (27.57+/-2.01)%, and (30.36+/-2.31)%, respectively. Resveratrol could down-regulate the expressions of HIF-1alpha, mdr1 and MRP1 significantly. After being treated with resveratrol at different concentrations separately, the expressions of HIF-1alpha, mdr1 and MRP1 in CNE2 cells decreased significantly as compared with paclitaxel alone or paclitaxel plus verapamil (P<0.01). CONCLUSION: Resveratrol can enhance the sensitivity of CNE2 cells to chemotherapeutic drugs under hypoxia. The potential mechanism is partly attributed to inhibiting the gene expressions of HIF-1alpha, mdr1 and MRP1.

Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy.

Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy. In this review, we summarized currently discovered driver mutations and corresponding signaling pathways, made an overview of identification methods of driver mutations and genes, and classified targeted drugs for HCC. The knowledge of mutational landscape deepen our understanding of carcinogenesis and promise future precision medicine for HCC patients.

Effect of A disintegrin and metalloproteinase 10 gene silencing on the proliferation, invasion and migration of the human tongue squamous cell carcinoma cell line TCA8113.

The present study aimed to investigate the effect of A disintegrin and metalloproteinase 10 (ADAM10) gene silencing on the proliferation, migration and invasion of the human tongue squamous cell carcinoma cell line TCA8113. RNA interference was used to knock down the expression of ADAM10 in the TCA8113 cell line and the proliferation, migration and invasive ability of the treated cells were observed in vitro. The expression levels of epidermal growth factor receptor (EGFR) and E-cadherin in the treated cells were determined by western blot analysis. The proliferation, migration and invasion abilities of cells in the ADAM10 siRNA-treated group were significantly lower than those in the control groups (P<0.05). In addition, compared with the control groups, the expression levels of EGFR and E-cadherin in the ADAM10 siRNA-treated cells were significantly decreased (P<0.05) and increased (P<0.05), respectively. These results suggested that ADAM10 is important in regulating the proliferation, invasion and migration of the human tongue squamous cell carcinoma cell line TCA8113 and that the mechanism may, at least in part, be associated with the upregulation of EGFR and the downregulation of E-cadherin.

Effective conversion of maize straw wastes into bio-hydrogen by two-stage process integrating H2 fermentation and MECs.

The enhanced H2 production from maize straw had been achieved through the two-stage process of integrating H2 fermentation and microbial electrolysis cells (MECs) in the present work. Several key parameters affecting hydrolysis of maize straw through subcritical H2O were optimized by orthogonal design for saccharification of maize straw followed by H2 production through H2 fermentation. The maximum reducing sugar (RS) content of maize straw reached 469.7 mg/g-TS under the optimal hydrolysis condition with subcritical H2O combining with dilute HCl of 0.3% at 230 °C. The maximum H2 yield, H2 production rate, and H2 content was 115.1 mL/g-TVS, 2.6 mL/g-TVS/h, and 48.9% by H2 fermentation, respectively. In addition, the effluent from H2 fermentation was used as feedstock of MECs for additional H2 production. The maximum H2 yield of 1060 mL/g-COD appeared at an applied voltage of 0.8 V, and total COD removal reached about 35%. The overall H2 yield from maize straw reached 318.5 mL/g-TVS through two-stage processes. The structural characterization of maize straw was also carefully investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) spectra.

Protective effect of dexmedetomidine on noise-induced hearing loss.

OBJECTIVES/HYPOTHESIS: Noise generated by instruments, such as mastoid or craniotomy drills, may cause hearing damage by reducing the cochlear blood flow (CoBF). This study investigated whether dexmedetomidine can lessen noise-induced hearing loss (NIHL) in a guinea pig model. STUDY DESIGN: Animal study using noise stimulation and measurement of hearing and CoBF in guinea pigs. METHODS: Guinea pigs (n = 8 animals/group) were treated by saline vehicle (control group), dexmedetomidine (1, 3, and 10 µg/kg dex groups), saline and noise (noise group), or 3 µg/kg dexmedetomidine and noise (dex+noise group). For noise exposure, octave band noise at 124 dB sound pressure level was administered to animals for 2 hours. Blood pressure (BP) and CoBF were monitored continuously. Auditory function was measured by the auditory brain-stem response (ABR) before and 1 hour, 3 hours, 8 hours, and 10 days after noise exposure. Plasma norepinephrine (NE) was measured at baseline and 30, 60, 90, and 120 minutes after noise exposure by high-performance liquid chromatography (HPLC). RESULTS: Noise exposure caused temporary and permanent hearing damage. Dexmedetomidine concentrations of 1 µg/kg and 3 µg/kg dose dependently improved CoBF. Administration of 10 µg/kg dexmedetomidine drastically reduced BP and CoBF. Pretreatment with 3 µg/kg dexmedetomidine alleviated the noise-induced reduction in CoBF and improved hearing function by decreasing the permanent and temporary threshold shifts. CONCLUSION: Dexmedetomidine displayed protective effects against NIHL in this animal model, suppressing activation of the sympathetic nervous system and improving CoBF. These findings could have clinical relevance and deserve further investigation.

Direct bioconversion of raw corn stalk to hydrogen by a new strain Clostridium sp. FS3.

A new strain FS3 which could achieve an efficient bioconversion of raw corn stalk to hydrogen had been isolated from anaerobic acclimated sludge, and identified as Clostridium butyricum on the basis of a series of physiological and biochemical experiments and 16S rDNA gene sequence. The strain could utilize various carbon sources to produce hydrogen. On the basis of single-factor experiments, the response surface methodology (RSM) was performed to optimize the media for hydrogen production. The maximum hydrogen yield of 92.9ml/g was observed under the optimal conditions: 20g/l raw corn stalk, 1.76g/l NH4HCO3, 0.91g/l KH2PO4 and 10.4ml/l nutrient solution. This finding opens a new avenue for direct conversion of raw cellulosic biomass to bio-hydrogen.

[Induction of apoptosis of leukemic tumor cells in mouse model with G-quadruplex ligand Tel03].

This study was aimed to investigate the anti-leukemia activity of Tel03 in vivo. The K562 xenografted leukemia model was established and mice were divided randomly into three groups. Mice of different group were treated with PBS (control), 5 mg/kg Tel03 or 15 mg/kg Tel03 (ip, twice a week) respectively. Tumor volume, body weight and other behavior were observed regularly. Cell apoptosis was detected with TUNEL assay and the expression levels of Bcl-2 and Bax were detected by Western blot. The results indicated that Tel03 exerted anti-leukemia activity in mouse model. Tel03 significantly reduced tumor volume in Tel03-treated group compared with control. In addition, 5 mg/kg Tel03 induced cell apoptosis without exerting apparent toxicity in mice. After Tel03 treatment, the expression of Bcl-2 was inhibited, however, the expression of Bax was up-regulated. It is concluded that G-quadruplex ligand Tel03 can induce cell apoptosis in leukemia mouse model, and this agent may be a potential anticancer drug.

[Surgical treatment of hyperthyroidism].

OBJECTIVE: In order to explore the management of peri-operation and the therapeutic effect in the surgical treatment of hyperthyroidism. METHODS: Fifty five cases of hyperthyroidism were undergone near-total thyroidectomy, during the operation recurrent laryngeal nerve was exposed, and the parathyroid was found with microscope when necessary. The third rank of inferior thyroid arteries were ligated to guarantee the blood supply for parathyroid. RESULTS: All cases underwent near-total thyroidectomy. There was no mortality, and no permanent recurrent laryngeal nerve palsy occurred, and no permanent hypoparathyroidism, and no recurrent hyperthyroidism. Follow-up was carried out 16 months to approximately 5 years after near-total thyroidectomy patients, Hypothyroidism occurred in 15 cases (57.7%), serum calcium levels were 2.15-2.45 mmol/L. CONCLUSIONS: Special attention should be given to the management of peri-operation, the above the method can prevent operative complication in the surgical treatment of hyperthyroidism, with excellent result.