Endothelialization of PTFE-covered stents for aneurysms and arteriovenous fistulas created in canine carotid arteries.

To investigate the endothelialization of covered and bare stents deployed in the canine carotid arteries and subclavian arteries for treating experimental aneurysms and arteriovenous fistulas, twenty aneurysms were created in 10 dogs, and 20 fistulas in another 10 dogs. The Willis balloon-expandable covered stent and a self-expandable covered stent were used to treat these lesions, and a self-expandable bare stent was deployed in the subclavian artery for comparison. Followed up for up to 12 months, the gross observation, pathological staining, and scanning electronic microscopic data were analyzed. Two weeks after creation of animal model, thirty self-expandable covered stents and ten balloon-expandable covered stents were deployed. Fifteen bare stents were deployed within the left subclavian arteries. Twenty days after stenting, the aneurysm significantly shrank. At 6 months, the thrombi within the aneurysm cavity were organized. Three to 12 months later, most covered and bare stents were covered by a thin transparent or white layer of endothelial intima. Layers of intima or pseudomembrane were formed on the stent 20-40 days after stent deployment. Over three months, the pseudomembrane became organized, thinner, and merged into the vascular wall. Under scanning electronic microscopy, the surface of covered and bare stents had only deposition of collagen fibers and rare endothelial cells 20-40 days after stenting. From three to ten months, the endothelial cells on the internal surface of stent became mature, with spindle, stripe-like or quasi round morphology along the blood flow direction. Over time, the endothelial cells became mature. In conclusion, three months after deployment in canines' arteries, the self-expandable bare and covered stents have mostly been covered by endothelial cells which become maturer over time, whereas the balloon-expandable covered stents do not have complete coverage of endothelial cells at three months, especially for protruding stent struts and areas. Over time, the endothelialization will become mature.

Effects of high-intensity focused ultrasound combined with levonorgestrel-releasing intrauterine system on patients with adenomyosis.

It is very important to treat adenomyosis which may cause infertility, menorrhagia, and dysmenorrhea for women at the reproductive age. High-intensity focused ultrasound (HIFU) is effective in destroying target tumor tissues without damaging the path of the ultrasound beam and surrounding normal tissues. The levonorgestrel-releasing intrauterine system (LN-IUS) is a medical system which is inserted into the uterine to provide medicinal treatment for temporary control of the symptoms caused by adenomyosis. This study was to investigate the effect of HIFU combined with the LN-IUS on adenomyosis. In the HIFU treatment, the parameters of the ultrasound were transmission frequency 0.8 MHz and input power 50-400 W (350 ± 30), and the temperature in the target tissue under these conditions would reach 60-100 °C (85 °C ± 6.3 °C). Size reduction and blood flow signal decrease were used to assess the effect of combined treatment. In this study, 131 patients with adenomyosis treated with HIFU combined with LN-IUS were retrospectively enrolled. The clinical and follow-up data were analyzed. After treatment, the volume of the uterine lesion was significantly decreased with an effective rate of 72.1%, and the adenomyosis blood flow signals were significantly reduced, with an effective rate of 71.3%. At six months, the menstrual cycle was significantly (P < 0.05) decreased from 31.4 ± 3.5 days before treatment to 28.6 ± 1.9 days, the menstrual period was significantly shortened from 7.9 ± 1.2 days before HIFU to 6.5 ± 1.3 days, and the menstrual volume was significantly (P < 0.05) decreased from 100 to 49% ± 13%. The serum hemoglobin significantly (P < 0.05) increased from 90.8 ± 6.2 g/L before treatment to 121.6 ± 10.8 g/L at six months for patients with anemia. Among seventy-two (92.3%) patients who finished the six-month follow-up, sixty-five (90.3%) patients had the dysmenorrhea completely relieved, and the other seven (9.7%) patients had only slight dysmenorrhea which did not affect their daily life. Adverse events occurred in 24 (18.3%) patients without causing severe consequences, including skin burns in two (1.5%) patients, skin swelling in four (3.1%), mild lower abdominal pain and low fever in 15 (11.5%), and subcutaneous induration in three (2.3%). Six months after treatment, no other serious side effects occurred in any patients with follow-up. In conclusions, the use of high-intensity focused ultrasound combined with the levonorgestrel-releasing intrauterine system for the treatment of adenomyosis is safe and effective even though the long-term effect remains to be confirmed.

Safety and effects of endovascular treatment of basilar tip aneurysms in patients with moyamoya diseases.

The effect and safety of endovascular treatment of basilar tip aneurysms associated with moyamoya disease are unknown. This study was to investigate the safety and effect of endovascular treatment of basilar tip aneurysms associated with moyamoya disease. Patients with moyamoya disease concurrent with basilar tip aneurysms were retrospectively enrolled and treated with endovascular embolization. The clinical and angiographic data were analyzed. Thirty patients with a basilar tip aneurysm were enrolled, including 8 (26.67%) male and 22 (73.33%) female patients aged 38 to 72 years (mean 54.4 ± 8.15). Endovascular treatment was successfully performed in 29 (96.67%) patients but failed in 1 (3.33%). Immediately after embolization, aneurysm occlusion degree was Raymond-Roy grade I in 26 (89.66%), grade II in 2 (6.90%), and grade III in 1 (3.45%). Intraprocedural complications occurred in 2 (10%) patients, including aneurysm rupture in 1 (3.33%), leading to death of the patient, and stent thrombosis in 2 (6.67%) which was successfully treated with thrombolysis. At discharge, good clinical outcome (modified Rankin Scale 0-2) was achieved in 29 (96.67%) and death in 1 (3.03%). Follow-up was performed 6 to 26 months (median 15) in 27 (93.1%) patients. Aneurysm occlusion degree was Raymond-Roy grade I in 21 (77.78%) patients, grade II in 4 (14.81%), and grade III in 2 (7.41%), not significantly (P = .67) different from those immediately after embolization. Aneurysm recurrence was found in 4 patients (14.81%). The clinical outcome was modified Rankin Scale 0 to 2 in all 27 patients, not significantly different from that at discharge. Endovascular embolization can be performed safely and effectively for basilar tip aneurysms associated with moyamoya disease even though more advanced embolization techniques are necessary.

A-kinase interacting protein 1 might serve as a novel biomarker for worse prognosis through the interaction of chemokine (C-X-C motif) ligand 1/chemokine (C-X-C motif) ligand 2 in acute myeloid leukemia.

BACKGROUND: This study aimed to explore the association of A-kinase interacting protein 1 (AKIP1) with chemokine (C-X-C motif) ligand (CXCL) 1/CXCL2, and further investigate their correlation with clinical features and prognosis in acute myeloid leukemia (AML) patients. METHODS: Totally 160 de novo AML patients were recruited, and their bone marrow samples were collected before treatment for detecting the expressions of AKIP1, CXCL1, and CXCL2 by the quantitative polymerase chain reaction. Complete remission (CR) was assessed after induction treatment, and event-free survival (EFS) and overall survival (OS) were calculated. RESULTS: AKIP1 expression was positively associated with CXCL1 (P < .001) and CXCL2 expression (P < .001). AKIP1 high expression was correlated with FAB classification (P = .022), monosomal karyotype (P = .001), and poor risk stratification (P = .013), while CXCL2 high expression was associated with monosomal karyotype (P = .001). As for treatment response, AKIP1 high expression exhibited a trend to be increased in non-CR patients compared with CR patients, while without statistical significance (P = .105). However, no correlation of CXCL1 (P = .418) or CXCL2 (P = .685) with CR achievement was observed. Most importantly, AKIP1 and CXCL1 were negatively correlated with accumulating EFS and OS (all P < .05), while CXCL2 only showed a trend to be negatively associated with accumulating EFS (P = .069) and OS (P = .055; but without statistical significance). CONCLUSION: AKIP1 might serve as a novel biomarker for worse AML prognosis through the interaction of CXCL1/CXCL2.

Swainsonine protects H9c2 cells against lipopolysaccharide-induced apoptosis and inflammatory injury via down-regulating miR-429.

Pediatric myocarditis (PM) is usually related to myocardial dysfunction. Generally, 30% of PM patients will die or undergo heart transplantation. Swainsonine (SW) is a natural alkaloid and an anti-cancer substance. Our goal was to determine the roles of SW in PM in current study. H9c2 cells were pre-treated by lipopolysaccharide (LPS). Viability and apoptosis were evaluated utilizing CCK-8 assay and flow cytometry. Inflammatory cytokines' mRNA expression and production were assessed by western blot and ELISA. Western blot was utilized to distinguish apoptosis and immune-related factors expression. Sequentially, the abovementioned parameters were reassessed when miR-429 was overexpressed. LPS declined viability as well as raised apoptosis and inflammatory injury in H9c2 cells. SW alleviated apoptosis and inflammatory injury induced by LPS. MiR-429 expression was elevated by LPS and suppressed by SW. SW-induced the increasing of viability and the reduction of inflammatory injury were reversed by overexpression of miR-429. Eventually, SW inhibited p38MAPK/NF-κB pathway which activated by LPS via overexpressing miR-429. SW exerted its anti-apoptosis and anti-inflammatory function in LPS-treated H9c2 cells through p38MAPK/NF-κB pathway and down-regulation of miR-429.

The prevalence, risk factors, and prognostic value of anxiety and depression in refractory or relapsed acute myeloid leukemia patients of North China.

This study aimed at investigating the prevalence of anxiety and depression, and their risk factors as well as their correlation with prognosis in refractory or relapsed (R/R) acute myeloid leukemia (AML) patients.A total of 180 R/R AML patients were enrolled and their anxiety and depression were assessed by Hospital Anxiety and Depression Scale (HADS) before treatment. Besides, HADS was also evaluated in 180 de novo AML patients prior treatment and 180 healthy controls (HCs), respectively.Both the HADS-Anxiety and HADS-Depression scores were increased in R/R AML patients compared with de novo AML patients and HCs (all P < .001). Meanwhile, the prevalence of anxiety and depression was 53.9% and 45.6% in R/R AML patients, which were also greatly higher compared with de novo AML patients and HCs (all P < .01). Regarding risk factors, higher Eastern Cooperative Oncology Group score and lines of salvage therapy were correlated with anxiety and depression in R/R AML patients (all P < .05). Furthermore, anxiety and depression were associated with shorter overall survival (OS) in R/R AML patients (all P < .05), while no association of different degrees of anxiety and depression with OS was observed (all P > .05).Anxiety and depression are highly prevalent and implicated in the management and prognosis of R/R AML.

Shikonin potentiates paclitaxel antitumor efficacy in esophageal cancer cells via the apoptotic pathway.

Shikonin is a natural naphthoquinone pigment that can suppress the growth of a number of cancer cell types. Paclitaxel is an antineoplastic chemotherapy drug, which is used for the treatment of various types of solid tumor cancer. However, acquired paclitaxel resistance results in the failure of therapy, and consequent metastasis and relapse. The aim of the present study was to investigate whether shikonin can sensitize esophageal cancer cells to paclitaxel-treatment and to elucidate the underlying mechanisms. The biological effects of these two agents on esophageal cancer cell lines KYSE270 and KYSE150 were investigated by MTT assay, cell cycle analysis, Annexin-V apoptosis assay, western blotting and reverse transcription-quantitative polymerase chain reaction. The results demonstrated that shikonin could significantly increase the cell growth inhibition effect induced by paclitaxel in the examined cell lines (P<0.001). The addition of shikonin to paclitaxel promoted cancer cell mitotic arrest and induced significantly higher levels of cell apoptosis. Notably, the mRNA and protein levels of Bcl-2 were downregulated, while p53 was upregulated in KYSE270 and KYSE150 cells following combined treatment. In summary, shikonin can sensitize esophageal cancer cells to paclitaxel-treatment by promoting cell mitotic arrest and reinforcing the susceptibility of esophageal cancer cells to apoptosis induced by paclitaxel, which is potentially associated with altered levels of Bcl-2 and p53.

Inorganic Nanomaterials as Carriers for Drug Delivery.

For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study.

Hybrid Mesoporous Silica-Based Drug Carrier Nanostructures with Improved Degradability by Hydroxyapatite.

Potential bioaccumulation is one of the biggest limitations for silica nanodrug delivery systems in cancer therapy. In this study, a mesoporous silica nanoparticles/hydroxyapatite (MSNs/HAP) hybrid drug carrier, which enhanced the biodegradability of silica, was developed by a one-step method. The morphology and structure of the nanoparticles were characterized by TEM, DLS, FT-IR, XRD, N2 adsorption-desorption isotherms, and XPS, and the drug loading and release behaviors were tested. TEM and ICP-OES results indicate that the degradability of the nanoparticles has been significantly improved by Ca(2+) escape from the skeleton in an acid environment. The MSNs/HAP sample exhibits a higher drug loading content of about 5 times that of MSNs. The biological experiment results show that the MSNs/HAP not only exhibits good biocompatibility and antitumor effect but also greatly reduces the side effects of free DOX. The as-synthesized hybrid nanoparticles may act as a promising drug delivery system due to their good biocompatibility, high drug loading efficiency, pH sensitivity, and excellent biodegradability.

Spatiotemporal drug release visualized through a drug delivery system with tunable aggregation-induced emission.

Tetraphenylethene and doxorubicin are assembled into a self-indicating drug delivery system (TD NPs). TD NPs are decomposed into DOX and TPE NPs in lysosome. Since TD NPs, TPE NPs and DOX are all fluorescent, the detachment of DOX from TPE NPs is accompanied by fluorescence changing. By observing the fluorescence changes, the spatiotemporal drug release is visualized.

Multifunctional hybrid silica nanoparticles for controlled doxorubicin loading and release with thermal and pH dually response.

Controlled drug loading and release into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to resistance and inefficient cellular uptake. Here a temperature and pH dually responsive PNiPAM/AA@SiO2 core-shell particles with internal controlled release were designed and fabricated for efficient cancer treatment, which could recognize the intrinsic pH differences between cancers and normal tissues. Upon lowering the temperature, doxorubicin was loaded into the PNiPAM/AA@SiO2 nanoparticles, whereas by increasing the acidity, previously loaded doxorubicin was quickly released. Comparing with common mesoporous silica particles (MSNs), this core-shell particle has more uniform size and better dispersity. In addition, dried PNiPAM/AA@SiO2 nanoparticles could be easily redispersed in distilled water. The in vitro cell culture experiments showed that not only PNiPAM/AA@SiO2 particles were more biocompatible and lower cytotoxic than MSN, but also DOX@PNiPAM/AA@SiO2 had higher drug releasing efficiency in the lysosomes and stronger inhibitory effect on tumor cell growth than DOX@MSN. All these features indicated that PNiPAM/AA@SiO2 particles have great potential in therapy applications.

Metallofullerene nanoparticles promote osteogenic differentiation of bone marrow stromal cells through BMP signaling pathway.

Although endohedral metallofullerenol [Gd@C(82)(OH)(22)](n) nanoparticles have anti-tumor efficiency and mostly deposit in the bones of mice, how these nanoparticles act in bone marrow stromal cells (MSCs) remains largely unknown. Herein, we observed that [Gd@C(82)(OH)(22)](n) nanoparticles facilitated the differentiation of MSCs toward osteoblasts, as evidenced by the enhancement of alkaline phosphatase (ALP) activity and mineralized nodule formation upon [Gd@C(82)(OH)(22)](n) nanoparticle treatment. Mechanistically, the effect of [Gd@C(82)(OH)(22)](n) nanoparticles on ALP activity was inhibited by the addition of noggin as an inhibitor of the BMP signaling pathway. Moreover, the in vivo results of the ovariectomized rats further indicated that [Gd@C(82)(OH)(22)](n) nanoparticles effectively improved bone density and prevented osteoporosis.

[Progress in biofixation of CO2 from combustion flue gas by microalgae].

Global warming caused by the increasing CO2 concentration in atmosphere is a serious problem in the international political, economic, scientific and environmental fields in recent years. Intensive carbon dioxide capture and storage (CCS) technologies have been developed for a feasible system to remove CO2 from industrial exhaust gases especially for combustion flue gas. In these technologies, the biofixation of CO2 by microalgae has the potential to diminish CO2 and produce the biomass. In this review, the current status focusing on biofixation of CO2 from combustion flue gases by microalgae including the selection of microalgal species and effect of flue gas conditions, the development of high efficient photobioreactor and the application of microalgae and its biomass product were reviewed and summarized. Finally, the perspectives of the technology were also discussed.

[The analysis method of the Hilbert spectrum entropy of dividing frequency range for signals of heart rate variability].

The signal analysis of heart rate variability (HRV) has been very significant for heart disease of aided diagnosis, monitoring and evaluation. We proposed a new method of HRV signal analysis based on the Hilbert spectrum entropy dividing frequency range. According to Hilbert spectrum characteristics of the multi-resolution and the characteristic of HRV signal frequency spectrum, the Hilbert time-frequency spectrum entropy of HRV signal in different frequency range and the full frequency Hilbert time-frequency spectrum entropy with weighting factor were calculated. This approach was analyzed after the appropriate separation for various physiological factors based on the frequency range and it is more conducive to reflect the physiological and the pathological characteristics. Applying the new approach to the actual HRV signal of the MIT-BIH standard database, we obtained the results which showed that this method could effectively differentiate from the sample group for the young, the elder and the patients with atrial fibrillation, and for the sample group for the healthy persons and CHF patients, the performance in statistical analysis was superior to those of the general time-frequency entropy method. The approach could provide an effective analysis method for clinical HRV signal.

[Adaptive de-noising of ECG signal based on stationary wavelet transform].

According to the limitations of wavelet threshold in de-noising method, we approached a combining algorithm of the stationary wavelet transform with adaptive filter. The stationary wavelet transformation can suppress Gibbs phenomena in traditional DWT effectively, and adaptive filter is introduced at the high scale wavelet coefficient of the stationary wavelet transformation. It would remove baseline wander and keep the shape of low frequency and low amplitude P wave, T wave and ST segment wave of ECG signal well. That is important for analyzing ECG signal of other feature information.