Bladder cancer selective chemotherapy with potent NQO1 substrate co-loaded prodrug nanoparticles.

Currently, clinical intravesical instillation chemotherapy has been greatly compromised by the toxicological and physiological factors. New formulations that can specifically and efficiently kill bladder cancer cells are in urgent need to overcome the low residence efficiency and dose limiting toxicity of current ones. The combination of mucoadhesive nanocarriers and cancer cell selective prodrugs can to great extent address these limitations. However, the insignificant endogenous stimulus difference between cancer cells and normal cells in most cases and the high local drug concentration make it essential to develop new drugs with broader selectivity-window. Herein, based on the statistically different NQO1 expression between cancerous and normal bladder tissues, the reactive oxygen species (ROS) activatable epirubicin prodrug and highly potent NQO1 substrate, KP372-1, was co-delivered using a GSH-responsive mucoadhesive nanocarrier. After endocytosis, epirubicin could be promptly activated by the NQO1-dependent ROS production caused by KP372-1, thus specifically inhibiting the proliferation of bladder cancer cells. Since KP372-1 is much more potent than some commonly used NQO1 substrates, for example, ß-lapachone, the cascade drug activation could occur under much lower drug concentration, thus greatly lowering the toxicity in normal cells and broadening the selectivity-window during intravesical bladder cancer chemotherapy.

High serum miR-484 expression is associated with the diagnosis and prognosis of patients with non-small cell lung cancer.

The aim of the current study was to assess the expression and clinical significance of serum microRNA (miR)-484 in patients with non-small cell lung cancer (NSCLC). Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of miR-484 in the serum of patients with NSCLC and NSCLC cell lines. Cell counting kit-8, flow cytometry, cell migration and cell invasion assays were performed to assess the role of miR-484 in the malignant changes associated with NSCLC cells. Furthermore, to assess the diagnostic value of miR-484, receiver operating curve (ROC) analysis was performed and the clinical relevance of serum miR-484 expression in patients with NSCLC was determined. A Kaplan-Meier analysis with the log-rank test was performed to assess the overall survival rate patients. To the best of our knowledge, the current study demonstrates for the first time that serum miR-484 was increased in patients with NSCLC compared with healthy controls. Additionally, serum miR-484 was revealed to be positively associated with histological grade, lymph node metastasis, distant metastasis and clinical stage. Patients with NSCLC and high serum miR-484 levels demonstrated significantly poorer overall survival rates compared with those exhibiting lower serum miR-484 expressions. ROC analysis revealed that serum miR-484 could screen patients with NSCLC patients from healthy controls with a high sensitivity and specificity. In vitro analysis also demonstrated that miR-484 was significantly upregulated in NSCLC cell lines, including 95D and H358 cells. Furthermore, the suppression of miR-484 decreased cell proliferation, cell migration and invasion. In summary, the results of the present study demonstrated that increased serum miR-484 expression is associated with the diagnosis and prognosis of patients with NSCLC.

A compact high-voltage pulse forming module with hundreds of nanoseconds quasi-squared output pulse.

A pulse forming module (PFM) with a multifunction of energy storage and a quasi-squared pulse output is developed to meet the challenge of a compact design and square output waveform in a high-power Marx generator. A simplified pulse forming circuit comprising only 2 parallel connected LC sections, in which every section contains an inductor and a capacitor in series, has been proposed and investigated carefully to obtain a quasi-squared waveform. Influences of inductance values in the circuit on its output waveform to a resistive load are investigated. PFMs are designed and fabricated based on the 2 LC section circuit, in which series folded film capacitors are employed to achieve a high energy density of 0.04 J/cm3 at a charging voltage of 120 kV. The as-designed module can output a quasi-squared waveform with FWHM of about 180 ns and the flattop duration greater than 90 ns. It can work at a repetition rate as high as 50 Hz, while the output waveforms show small differences. This research has developed a PFM with a quasi-squared output waveform based on a simplified 2 LC section circuit, which shows potential to reduce the size of the high power generator system that is based on it.

Higher expression of circulating miR-182 as a novel biomarker for breast cancer.

MicroRNAs (miRNAs), present in the serum in a stable and reproducible manner, may be used as biomarkers for various diseases. Few studies have previously investigated circulating miRNAs in the peripheral blood of breast cancer (BC) patients. To identify the role of serum miR-182 levels in BC, the present study detected miR-182 levels in the serum of 46 BC patients and 58 controls, by quantitative PCR. The results showed that the serum miR-182 levels in BC patients were significantly higher compared with the serum of healthy controls (P<0.01). The miR-182 was also overexpressed in the BC tissues compared with the para-carcinoma tissues. Furthermore, the serum levels of miR-182 in the estrogen receptor (ER)-positive patients were considerably lower compared with those in the ER-negative patients. The serum levels of miR-182 in the progesterone receptor (PR)-positive patients were also found to be lower compared with those in the PR-negative patients. The current study highlights results consistent with miR-182 as a novel and valuable biomarker for the diagnosis of BC.

[Effects of adhesion releasing under nerve block and arthrolysis on adhesive scapulohumeral periarthritis: a comparative study].

OBJECTIVE: To compare the effects of adhesion releasing under nerve block and arthrolysis on adhesive scapulohumeral periarthritis. METHODS: Sixty patients with adhesive scapulohumeral periarthritis 24 males and 36 females, aged 52.5 (40 - 67), were randomly divided into 4 equal groups: Group I, undergoing adhesion releasing under brachial plexus block, Group II, undergoing adhesion releasing under stellate ganglion block, Group III, undergoing limited adhesion releasing under stellate ganglion block, and Group IV undergoing arthrolysis under stellate ganglion block. The clinical effects were recorded and compared. RESULTS: The short-term effect of Group IV was significantly superior to the other 3 groups (all P < 0.05). The frequency of block + manipulation treatment of Group I was significantly less than those of the other 3 groups (all P < 0.01), and the frequency of pain point injection of Group I was significantly higher than those of the other 3 groups (all P < 0.01). CONCLUSION: The 4 methods are all effective for the treatment of adhesive scapulohumeral periarthritis. In particular, arthrolysis under stellate ganglion block shows greater improvement in the joint function and less uncomfortableness caused by numbness and weakness of the arm.