Efficacy and safety of Wuhu oral liquid in treating acute soft tissue injuries: a multicenter, randomized, double-blind, double-dummy, parallel-controlled trial.

Background: Wuhu Oral Liquid (WHOL) is a modified preparation derived from the famous Wuhu Powder, which has a long history of use in treating traumatic injuries. This preparation has anti-inflammatory and analgesic properties and accelerates recovery following acute soft tissue injuries. Aims: To evaluate the efficacy and safety of WHOL in treating acute soft tissue injury associated with qi stagnation and blood stasis syndrome and to provide a basis for applying for the protection of varieties of Chinese medicine for WHOL. Methods: This study was a randomized, controlled, double-blind, multicenter clinical trial in which Fufang Shang Tong Capsule (FFSTC) was selected as the control drug. A total of 480 subjects with acute soft tissue injury associated with qi stagnation and blood stasis syndrome were randomly divided into a test and control group in a 3:1 ratio. The duration of drug treatment was 10 days. The primary outcome was Visual Analogue Scale (VAS) score for pain (including pain at rest and pain on activity). Secondary outcomes included the disappearance time of the pain at rest and on activity; the curative effect of TCM syndrome and improvement in the individual symptoms of TCM (swelling, ecchymosis, and dysfunction); and changes in C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Safety was assessed using vital signs, laboratory examinations, electrocardiograms, and physical examinations. Results: Patient compliance was satisfactory in both groups (all between 80% and 120%). After 4 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain at rest (-1.88 ± 1.13 vs. -1.60 ± 0.93, p < 0.05) and on activity (-2.16 ± 1.18 vs. -1.80 ± 1.07, p < 0.05). After 7 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain on activity (-3.87 ± 1.60 vs. -3.35 ± 1.30, p < 0.01) and improving swelling (cure rate: 60.4% vs. 46.2%, p < 0.05; obvious effective rate: 60.7% vs. 47.0%, p < 0.05). After 10 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the levels of CRP (-0.13 ± 2.85 vs. 0.25 ± 2.09, p < 0.05) and improving the TCM syndrome (cure rate: 44.1% vs. 30.8%, p < 0.05) and swelling (cure rate: 75.6% vs. 67.5%, p < 0.01; obvious effective rate: 75.6% vs. 68.4%, p < 0.05; effective rate: 77.0% vs. 71.8%, p < 0.05). The disappearance time of pain at rest was 8 days in both groups and 9 days on activity in both groups. In addition, there was no statistical difference between the incidence of adverse events (4.5% vs. 2.6%, p > 0.05) and adverse reactions (0.3% vs. 0%, p > 0.05) between the WHOL group and the FFSTC group. No serious adverse events occurred in either group, and no subjects were withdrawn because of adverse events. Conclusion: WHOL relieves the symptoms caused by acute soft tissue injury associated with qi stagnation and blood stasis syndrome more rapidly than FFSTC, and it is effective and safe in the treatment of acute soft tissue injury. Future studies still need a larger sample size to verify its efficacy and safety. Clinical Trial Registration: https:// www.chictr.org.cn/showproj.html?proj=149531, Identifier ChiCTR2200056411.

MVKT-ECG: Efficient single-lead ECG classification for multi-label arrhythmia by multi-view knowledge transferring.

Electrocardiogram (ECG) is a widely used technique for diagnosing cardiovascular disease. The widespread emergence of smart ECG devices has sparked the demand for intelligent single-lead ECG-based diagnostic systems. However, it is challenging to develop a single-lead-based ECG interpretation model for multiple disease diagnosis due to the lack of some key disease information. We aim to improve the diagnostic capabilities of single-lead ECG for multi-label disease classification in a new teacher-student manner, where the teacher trained by multi-lead ECG educates a student who observes only single-lead ECG We present a new disease-aware Contrastive Lead-information Transferring (CLT) to improve the mutual disease information between the single-lead-based ECG interpretation model and multi-lead-based ECG interpretation model. Moreover, We modify the traditional Knowledge Distillation into Multi-label disease Knowledge Distillation (MKD) to make it applicable for multi-label disease diagnosis. The whole knowledge transferring process is inter-lead Multi-View Knowledge Transferring of ECG (MVKT-ECG). By employing the training strategy, we can effectively transfer comprehensive disease knowledge from various views of ECG, such as the 12-lead ECG, to a single-lead-based ECG interpretation model. This enables the model to extract intricate details from single-lead ECG signals and enhances the model's capability of diagnosing and identifying single-lead signals. Extensive experiments on two commonly used public multi-label datasets, ICBEB2018 and PTB-XL demonstrate that our MVKT-ECG yields exceptional diagnostic performance improvements for single-lead ECG. The student outperforms its baseline observably on the PTB-XL dataset (1.3 % on PTB.super, and 1.4 % on PTB.sub), and on ICBEB2018 dataset (3.2 %).

Synthesis and Characterization of [Fe3 (As3 )3 (As4 )]3- , a Binary Fe/As Zintl Cluster With an Fe3 Core.

We report here the synthesis and structural characterization of the first binary iron arsenide cluster anion, [Fe3 (As3 )3 (As4 )]3- , present in both [K([2.2.2]crypt)]3 [Fe3 (As3 )3 (As4 )] (1) and [K(18-crown-6)]3 [Fe3 (As3 )3 (As4 )]⋅en (2). The cluster contains an Fe3 triangle with three short Fe-Fe bond lengths (2.494(1) Å, 2.459(1) Šand 2.668(2) Šfor 1, 2.471(1) Å, 2.473(1) Šand 2.660(1) Šfor 2), bridged by a 2-butene-like As4 unit. An analysis of the electronic structure using DFT reveals a triplet ground state with direct Fe-Fe bonds stabilizing the Fe3 core.

Synthesis and characterisation of the ternary intermetalloid clusters {M@[As8(ZnMes)4]}3- (M = Nb, Ta) from binary [M@As8]3- precursors.

The development of rational synthetic routes to inorganic arsenide compounds is an important goal because these materials are finding applications in many areas of materials science. In this paper, we show that the binary crown clusters [M@As8]3- (M = Nb, Ta) can be used as synthetic precursors which, when combined with ZnMes2, generate ternary intermetalloid clusters with 12-vertex cages, {M@[As8(ZnMes)4]}3- (M = Nb, Ta). Structural studies are complemented by mass spectrometry and an analysis of the electronic structure using DFT. The synthesis of these clusters presents new opportunities for the construction of As-based nanomaterials.

Synthesis and Characterization of Ternary Clusters Containing the [As16]10- Anion, [MM'As16]4- (M = Nb or Ta; M' = Cu or Ag).

The [Nb@As8]3- anion was first isolated from solution in 1986, and a number of isostructural [M@Pn8]n- clusters (M = Nb, Cr, or Mo; Pn = As or Sb; n = 2 or 3) have since been reported. We show here how anions of this class can be used as synthetic precursors that, in combination with sources of low-valent late transition metals (Cu and Ag), generate ternary polyarsenide cluster anions with unprecedented structural motifs. Chain type [MM'As16]4- (M = Nb or Ta; M' = Cu or Ag) units are found in compounds 2-5. These clusters contain a nortricyclane-like As7 cage and a [M@As8] crown, linked by a single As atom, and represent a fusion of two quite distinct branches of polyarsenide chemistry. Our analysis of the electronic structure confirms that the cluster retains many of the features of the component units. Electrospray ionization mass spectrometry reveals a series of smaller component ions containing 8-12 As atoms, the density functional theory-computed structures of which can be understood in terms of the pseudoelement concept. This work not only presents a new type of coordination mode for As clusters but also offers a point of entry for the rational design of multinary arsenic-based materials.

End-to-end keyword search system based on attention mechanism and energy scorer for low resource languages.

Keyword search (KWS) means searching for keywords given by the user from continuous speech. Conventional KWS systems are based on Automatic Speech Recognition (ASR), where the input speech has to be first processed by the ASR system before keyword searching. In the recent decade, as deep learning and deep neural networks (DNN) become increasingly popular, KWS systems can also be trained in an end-to-end (E2E) manner. The main advantage of E2E KWS is that there is no need for speech recognition, which makes the training and searching procedure much more straightforward than the traditional ones. This article proposes an E2E KWS model, which consists of four parts: speech encoder-decoder, query encoder-decoder, attention mechanism, and energy scorer. Firstly, the proposed model outperforms the baseline model. Secondly, we find that under various supervision, character or phoneme sequences, speech or query encoders can extract the corresponding information, resulting in different performances. Moreover, we introduce an attention mechanism and invent a novel energy scorer, where the former can help locate keywords. The latter can make final decisions by considering speech embeddings, query embeddings, and attention weights in parallel. We evaluate our model on low resource conditions with about 10-hour training data for four different languages. The experiment results prove that the proposed model can work well on low resource conditions.

Application of Delphi method in screening of indexes for measuring soil pollution value evaluation.

Soil pollution is one of the most important issues in environmental governance at present. Using scientific and reasonable methods to estimate the economic losses caused by soil pollution is the basis for maximizing the effectiveness of governance resources. This study combines the methods of mixed group discussion and literature analysis to establish preliminary soil pollution value loss measurement indicators. The Delphi method is used to modify, add, and delete indicators to obtain a set of feasible soil pollution value loss measurement indicator systems. It laid a method foundation for further quantifying the loss of soil pollution value and provided support to related government decisions such as land resource management and soil pollution control. The response coefficients of the two rounds of expert consultations were 81.2% and 77.8%; the degree of expert authority was 0.647 and 0.708; the coordination coefficients were 0.155 and 0.194; the final indicator system included three dimensions of economic, social, and environmental, a total of eight indicators. The experts in the soil pollution value loss measurement index system established in this study have unified final opinions and a good degree of coordination, which can be used to measure soil pollution value loss.

Sustainable Ligand-Free, Palladium-Catalyzed Suzuki-Miyaura Reactions in Water: Insights into the Role of Base.

A simple and efficient system was developed for the ligand-free Pd-catalyzed Suzuki-Miyaura reaction in water under mild conditions. Quaternary ammonium hydroxides with long chains were found to be very suitable bases. This ligand-free Pd-catalyzed Suzuki-Miyaura reaction showed improved durability in water with Pd loadings decreased to ppm level. Bases were shown to stabilize active palladium species in addition to acting as a base during the catalytic process. In the catalytic system with a strong base, the soluble active PdII ion exhibited anti-reduction properties, which prevented aggregation and deactivation of Pd species. The entire catalytic system could be recycled after separating the product by simple filtration. The water-compatible and air-stable effective catalytic protocol described herein represents an attractive and green synthetic advance in Suzuki-Miyaura couplings.

"On Water" Catalytic Aldol Reaction between Isatins and Acetophenones: Interfacial Hydrogen Bonding and Enamine Mechanism.

"On water" catalytic aldol reaction catalyzed by polyetheramine (D230) has been developed for easy access to 3-substituted 3-hydroxyindolin-2-ones through the reaction between various substituted isatins and acetophenones/cyclic ketones in high yields under room temperature. Systematic mechanism investigation uncovers the secret for the on water catalytic aldol reaction: comparison of the heterogeneous and homogeneous reaction circumstances with yields of 95 and 20%, respectively, indicates the on-water reaction dominating; interfacial hydrogen bonding between isatin with H2O is tested based on the downfield shift of the C2 and C3's 13C NMR signals when water was added to the CDCl3 solution of isatin; Lewis base polyetheramine D230 catalyzes the aldol reaction via the enamine mechanism verified by in situ NMR and ESI-MS analysis.

Serum levels of chromogranins and secretogranins correlate with the progress and severity of Parkinson's disease.

Little is known about the relevance of chromogranins (Cgs) and secretogranins (Sgs) in Parkinson's disease (PD). In this study, we determined serum levels of CgA, CgB, and SgII in PD patients and assessed their association with disease severity. PD patients were recruited, identified, and classified as having early (n = 14), intermediate (n = 18), or late (n = 4) stage disease according to Hoehn-Yahr scores. The serum concentrations of CgA, CgB, and SgII in patients with well-defined PD (n = 36) and in healthy controls (n = 52) were measured by enzyme-linked immunosorbent assay. Compared with controls, serum CgA levels were significantly elevated and serum SgII levels were significantly reduced in PD patients (both P < 0.05). There was no difference in serum CgB levels between the two groups. Both serum CgA and SgII levels changed progressively over time from early to intermediate to late stage (P < 0.05). Spearman correlation analysis revealed that serum CgA and SgII levels correlated with Hoehn-Yahr and UPDRS scores (P < 0.001). These results indicate that changes in serum levels of CgA and SgII may be closely related to the severity of PD.

A robust multifunctional ligand-controlled palladium-catalyzed carbonylation reaction in water.

A novel, hydrophilic and recyclable methoxypolyethylene glycol (PEG)-modulated s-triazine-based multifunctional Schiff base/N,P-ligand L9 was prepared and used in Pd-catalyzed Heck-type carbonylative coupling reactions, affording diverse chalcone derivatives and 1,4-dicarbonyl esters in good yields.

House dust mite extract induces growth factor expression in nasal mucosa by activating the PI3K/Akt/HIF-1α pathway.

Growing evidence suggests that hypoxia-inducible factor-α (HIF-1α) plays an important role in the progression of allergic airway inflammation and remodeling. However, the biochemical mechanisms leading to the activation of HIF-1α and the effects of HIF-1α on the expression of growth factors, including vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and fibroblast growth factor-2 (FGF-2), in allergic nasal inflammation are not clear. We examined the relationship between HIF-1α activation and production of VEGF, TGF-ß1, and FGF-2 in primary cultured nasal epithelial cells (NECs) after stimulation with house dust mite (HDM) extract. Moreover, we evaluated the importance of phosphoinositide3-kinase(PI3K)/Akt signaling in HDM-induced production of these growth factors in vitro and in the nasal mucosa of a murine model of allergic rhinitis (AR). Our results indicate HDM extract induced the expression of VEGF, TGF-ß1, and FGF-2 by activating the PI3K/Akt/HIF-1α pathway in human primary cultured NECs and in the nasal mucosa of a murine model. HIF-1α regulated the expression of VEGF, TGF-ß1, and FGF-2 in the nasal mucosa through direct and indirect pathways, which suggested that targeting the HIF-1α pathway could be a novel therapeutic approach for reducing nasal airway inflammation and remodeling in AR.

Differential distribution patterns of ammonia-oxidizing archaea and bacteria in acidic soils of Nanling National Nature Reserve forests in subtropical China.

In addition to ammonia-oxidizing bacteria (AOB) the more recently discovered ammonia-oxidizing archaea (AOA) can also oxidize ammonia, but little is known about AOA community structure and abundance in subtropical forest soils. In this study, both AOA and AOB were investigated with molecular techniques in eight types of forests at surface soils (0-2 cm) and deep layers (18-20 cm) in Nanling National Nature Reserve in subtropical China. The results showed that the forest soils, all acidic (pH 4.24-5.10), harbored a wide range of AOA phylotypes, including the genera Nitrosotalea, Nitrososphaera, and another 6 clusters, one of which was reported for the first time. For AOB, only members of Nitrosospira were retrieved. Moreover, the abundance of the ammonia monooxygenase gene (amoA) from AOA dominated over AOB in most soil samples (13/16). Soil depth, rather than forest type, was an important factor shaping the community structure of AOA and AOB. The distribution patterns of AOA and AOB in soil layers were reversed: AOA diversity and abundances in the deep layers were higher than those in the surface layers; on the contrary, AOB diversity and abundances in the deep layers were lower than those in the surface layers. Interestingly, the diversity of AOA was positively correlated with pH, but negatively correlated with organic carbon, total nitrogen and total phosphorus, and the abundance of AOA was negatively correlated with available phosphorus. Our results demonstrated that AOA and AOB were differentially distributed in acidic soils in subtropical forests and affected differently by soil characteristics.

Tumor-specific pH-responsive peptide-modified pH-sensitive liposomes containing doxorubicin for enhancing glioma targeting and anti-tumor activity.

The pH environment in gliomas is acidic. Therefore, in the present research, we selected our previously reported tumor-specific pH-responsive peptide H7K(R2)2 as a targeting ligand, which could respond to the acidic pH environment in gliomas, possessing CPP characteristics. The pH-sensitive liposomes were selected as carriers which could also respond to the acidic pH environment in gliomas triggering encapsulated drug release from these pH-sensitive liposomes. The H7K(R2)2-modified pH-sensitive liposomes containing doxorubicin (DOX-PSL-H7K(R2)2) were designed and prepared in order to evaluate their potential targeting of glioma tumor cells and their anti-tumor activity in mice with glioma tumor cells. DOX-PSL-H7K(R2)2 was prepared by the thin-film hydration method followed by remote loading using an ammonium sulfate gradient method. The in vitro release of DOX from pH-sensitive liposomes was tested and the in vitro targeting characteristics of H7K(R2)2-modified liposomes regarding C6 (rat C6 glioma cells) and U87-MG (human glioblastoma cells) were evaluated. The in vivo anti-tumor activity of DOX-PSL-H7K(R2)2 was also investigated in C6 tumor-bearing mice and in U87-MG orthotopic tumor-bearing nude mice. A specific targeting effect triggered by an acidic pH was observed in our in vitro experiments in C6 and U87-MG glioma cells. The pH-triggered DOX release from the pH-sensitive liposomes under acidic conditions was also confirmed in our in vitro experiment. Anti-tumor activity of DOX-PSL-H7K(R2)2 was found in C6 tumor-bearing mice and U87-MG orthotopic tumor-bearing nude mice in in vivo experiments. The antiangiogenic activity of DOX-PSL-H7K(R2)2 was confirmed in C6 tumor-bearing mice in the in vivo experiment. These H7K(R2)2-modified pH-sensitive liposomes containing anti-tumor drugs developed in this study are a promising delivery system involving the response stimuli at the acidic pH in the glioma tumor microenvironment and are suitable for anti-tumor therapy.

Does ligand-receptor mediated competitive effect or penetrating effect of iRGD peptide when co-administration with iRGD-modified SSL?

Ligand-mediated targeting of anticancer therapeutic agents is a useful strategy for improving anti-tumor efficacy. It has been reported that co-administration of a tumor-penetrating peptide iRGD (CRGDK/RGPD/EC) enhances the efficacy of anticancer drugs. Here, we designed an experiment involving co-administration of iRGD-SSL-DOX with free iRGD to B16-F10 tumor bearing mice to examine the action of free iRGD. We also designed an experiment to investigate the location of iRGD-modified SSL when co-administered with free iRGD or free RGD to B16-F10 tumor bearing nude mice. Considering the sequence of iRGD, we selected the GPDC, RGD and CRGDK as targeting ligands to investigate the targeting effect of these peptides compared with iRGD on B16-F10 and MCF-7 cells, with or without enzymatic degradation. Finally, we selected free RGD, free CRGDK and free iRGD as ligand to investigate the inhibitory effect on RGD-, CRGDK- or iRGD-modified SSL on B16-F10 or MCF-7 cells. Our results indicated that iRGD targeting to tumor cells was ligand-receptor mediated involving RGD to αv-integrin receptor and CRGDK to NRP-1 receptor. Being competitive effect, the administration of free iRGD would not be able to further enhance the anti-tumor activity of iRGD-modified SSL. There is no need to co-administrate of free iRGD with the iRGD-modified nanoparticles for further therapeutic benefit.

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo.

Clotted plasma proteins are present on the walls of tumor vessels and in tumor stroma. Tumor-homing peptide Cys-Arg-Glu-Lys-Ala (CREKA) could recognize the clotted plasma proteins in tumor vessels. Thermosensitive liposomes could immediately release the encapsulated drug in the vasculature of the heated tumor. In this study, we designed a novel form of targeted thermosensitive liposomes, CREKA-modified lysolipid-containing thermosensitive liposomes (LTSLs), containing doxorubicin (DOX) (DOX-LTSL-CREKA), to investigate the hypothesis that DOX-LTSL-CREKA might target the clotted plasma proteins in tumor vessels as well as tumor stroma and then exhibit burst release of the encapsulated DOX at the heated tumor site. We also hypothesized that the high local drug concentration produced by these thermosensitive liposomes after local hyperthermia treatment will be useful for treatment of multidrug resistance. The multidrug-resistant human breast adenocarcinoma (MCF-7/ADR) cell line was chosen as a tumor cell model, and the targeting and immediate release characteristics of DOX-LTSL-CREKA were investigated in vitro and in vivo. Furthermore, the antitumor activity of DOX-LTSL-CREKA was evaluated in MCF-7/ADR tumor-bearing nude mice in vivo. The targeting effect of the CREKA-modified thermosensitive liposomes on the clotted plasma proteins was confirmed in our in vivo imaging and immunohistochemistry experiments. The burst release of this delivery system was observed in our in vitro temperature-triggered DOX release and flow cytometry analysis and also by confocal microscopy experiments. The antitumor activity of the DOX-LTSL-CREKA was confirmed in tumor-bearing nude mice in vivo. Our findings suggest that the combination of targeting the clotted plasma proteins in the tumor vessel wall as well as tumor stroma by using CREKA peptide and temperature-triggered drug release from liposomes by using thermosensitive liposomes offers an attractive strategy for chemotherapeutic drug delivery to tumors.

Electro-response characteristic of starch hydrogel crosslinked with Glutaraldehyde.

The facile synthesis of the starch hydrogel with anisotropic microstructure and dynamic behaviors was developed in the presence (A-gel) and absence of DC electric field (B-gel). The microstructures of hydrogels were characterized by environmental scanning electron microscope. Their electro-responsive property of hydrogels was investigated with their storage modulus (G'). The result demonstrates that the G' of A-gel is greater than that of B-gel, and the modulus of A-gel increases along with the external field, which signifies positive electroresponse. In addition, the G' of A-gel and B-gel ((G'(A) and G'(B)) also continuously increases with increasing starch concentration, whereas both the maximum of modulus increment (ΔG' = G'(A)−G'(B) ) and that of modulus increment sensitivity (ΔG'/G'(B)) occur with the starch weight fraction at around 36.5%. To enhance the electro-responsive effects of the hydrogels, dielectric particles were dispersed in the hydrogel. It is found that BaTiO3/chitosan core-shell composite particles significantly enhance the electroresponse of the hydrogel. The mechanism of the electro-response mode is proposed.

Confocal and fluorescence lifetime imaging sheds light on the fate of a pyrene-tagged carbon monoxide-releasing Fischer carbene chromium complex.

The synthesis of a new pyrene-containing Fischer carbene complex is described. The complex has a broad absorbance spectrum between 300 and 400 nm and, on excitation at 345 nm in CH2Cl2 solution, emission is observed at 395 and 415 nm. Emission is also observed in PBS buffer, but in this case the resulting spectra are much broader. Confocal and fluorescence lifetime imaging indicate that emission occurs on treating HeLa cells with the complex and co-localisation studies demonstrate that this is from the mitochondria and lipid-rich regions of the cell.

Antitumor effect of iRGD-modified liposomes containing conjugated linoleic acid-paclitaxel (CLA-PTX) on B16-F10 melanoma.

In the present study, we prepared a novel delivery system of iRGD (CRGDK/RGPD/EC)-modified sterically stabilized liposomes (SSLs) containing conjugated linoleic acid-paclitaxel (CLA-PTX). The anti-tumor effect of iRGD-SSL-CLA-PTX was investigated on B16-F10 melanoma in vitro and in vivo. The in vitro targeting effect of iRGD-modified SSLs was investigated in a real-time confocal microscopic analysis experiment. An endocytosis-inhibition assay was used to evaluate the endocytosis pathways of the iRGD-modified SSLs. In addition, the in vitro cellular uptake and in vitro cytotoxicity of iRGD-SSL-CLA-PTX were evaluated in B16-F10 melanoma cells. In vivo biodistribution and in vivo antitumor effects of iRGD-SSL-CLA-PTX were investigated in B16-F10 tumor-bearing mice. The induction of apoptosis by iRGD-SSL-CLA-PTX was evaluated in tumor-tissue sections. Real-time confocal microscopic analysis results indicated that the iRGD-modified SSLs internalized into B16-F10 cells faster than SSLs. The identified endocytosis pathway of iRGD-modified SSLs indicated that energy- and lipid raft-mediated endocytosis played a key role in the liposomes' cellular uptake. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-SSL-CLA-PTX-treated group was 1.9-, 2.4-, or 2.1-fold compared with that in the CLA-PTX group after a 2-, 4-, or 6-hour incubation, respectively. In the biodistribution test, the CLA-PTX level in tumor tissues from iRGD-SSL-CLA-PTX-treated mice at 1 hour (1.84±0.17 µg/g) and 4 hours (1.17±0.28 µg/g) was 2.3- and 2.0-fold higher than that of CLA-PTX solution at 1 hour (0.79±0.06 µg/g) and 4 hours (0.58±0.04 µg/g). The value of the area under the curve for the first 24 hours in the tumors of iRGD-SSL-CLA-PTX-treated mice was significantly higher than that in the SSL-CLA-PTX and CLA-PTX solution-treated groups (P<0.01). The in vivo antitumor results indicated that iRGD-SSL-CLA-PTX significantly inhibited the growth of B16-F10 tumors compared with the SSL-CLA-PTX or CLA-PTX solution-treatment groups (P<0.01). The results of tumor-cell apoptosis showed that tumors from the iRGD-SSL-CLA-PTX-treated group exhibited more advanced cell apoptosis compared with the control, CLA-PTX solution-, and SSL-CLA-PTX-treated groups. In conclusion, the antitumor effect of iRGD-SSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo.

Expression of stanniocalcin-1 and stanniocalcin-2 in laryngeal squamous cell carcinoma and correlations with clinical and pathological parameters.

BACKGROUND: Stanniocalcin-1 (STC1) and stanniocalcin-2 (STC2) are secreted glycoprotein hormones involved in various types of human malignancies. The roles of STC1 and STC2 in laryngeal squamous cell carcinoma (LSCC) remain unknown. We investigated correlations between STC1 and STC2 expression and clinicopathological or prognostic factors in LSCC. METHODS: Pre-surgical peripheral blood samples were collected between 2012 and 2013 from 62 patients with LSCC. Quantitative RT-PCR analysis was performed to examine mRNA levels of STC1 and STC2. Immunohistochemistry was performed to retrospectively analyze 90 paraffin-embedded LSCC tissue samples, which were obtained from patients who received surgery between 2006 and 2009. These patients did not have histories of treatment or malignancies. Univariate analysis of patient survival was performed by the Kaplan-Meier method. Multivariate analyses were performed with the Cox proportional hazards model. RESULTS: The relative mRNA levels of STC1 and STC2 in peripheral blood were significantly greater in LSCC patients than those of healthy volunteers (both P<0.05). STC2 protein expression in tumor tissues was associated with invasion into the thyroid cartilage, T-Stage, lymphatic metastasis, clinical stage, and pathological differentiation (all P<0.05). In addition, STC2 protein expression was an independent prognostic factor for overall survival in patients with LSCC (P = 0.025). In contrast, STC1 expression only correlated with clinical stage (P = 0.026) and was not an independent or significant prognostic factor. CONCLUSIONS: Circulating STC1 and STC2 mRNA are potentially useful blood markers for LSCC. Our results strongly suggest that the STC2 protein, but not STC1, may be a valuable biomarker for LSCC malignancies and a prognostic marker for poor outcome following surgery. Future studies should examine STC2 as a novel molecular target for the treatment of LSCC.