Search

The tumor microenvironment (TME) featured by immunosuppression and hypoxia is pivotal to cancer deterioration and metastasis. Thus, regulating the TME to improve cancer cell ablation efficiency has received extensive interest in oncotherapy. However, to reverse the immunosuppression and alleviate hypoxia simultaneously in the TME are major challenges for effective cancer therapy. Herein, a multifunctional platform based on Au nanoparticles and a carbon dots modified hollow black TiO

Although previous studies have focused on the associations between peer group relations and cyber-aggression, limited attention has been paid to the heterogeneity in the functions of cyber-aggression. This study explored the unique associations of peer relations with proactive and reactive cyber-aggression and the possible mechanisms underlying them in a sample of adolescents using a longitudinal study design. A total of 829 middle school students completed the Cyber-rage and Cyber-reward Aggression Subscales of the Cyber-Aggression Typology Questionnaire, the Peer Relations Scale, the Social Information Processing-Attributional Bias Questionnaire, and the Self-efficacy for Aggression Scale twice at a 6-month interval. Multiple mediation analyses and bootstrapping were conducted using the Mplus 8 software. The results indicated that satisfying peer relations were negatively correlated with reactive cyber-aggression and positively associated with proactive cyber-aggression. Moreover, hostile intent attribution and self-efficacy for aggression mediated the associations between peer relations and both functions of cyber-aggression, however, in different ways. Unsatisfying peer relations were associated with higher levels of hostile intent attribution and lower levels of self-efficacy for aggression and predicted increases in reactive cyber-aggression. In contrast, satisfying peer relations were associated with lower levels of hostile intent attribution and higher levels of self-efficacy for aggression and predicted increases in proactive cyber-aggression. The findings indicated that different functions of cyber-aggression might be related to different mediation mechanisms, which sheds light on the prevention of cyber-aggression in the future.

Synovial macrophage polarization and inflammation are essential for osteoarthritis (OA) development, yet the molecular mechanisms and regulation responsible for the pathogenesis are still poorly understood. Here, we report that pseudolaric acid B (PAB) attenuated articular cartilage degeneration and synovitis during OA. PAB, a diterpene acid, specifically inhibited NF‐κB signalling and reduced the production of pro‐inflammatory cytokines, which further decreased M1 polarization and vessel formation. We further provide in vivo and in vitro evidences that PAB suppressed NF‐κB signalling by stabilizing PPARγ. Using PPARγ antagonist could abolish anti‐inflammatory effect of PAB and rescue the activation of NF‐κB signalling during OA. Our findings identify a previously unrecognized role of PAB in the regulation of OA and provide mechanisms by which PAB regulates NF‐κB signalling through PPARγ, which further suggest targeting synovial inflammation or inhibiting vessel formation at early stage could be an effective preventive strategy for OA.

Knotted suture bridge repair (KSBR) has been widely proven to be an effective method for rotator cuff repairs. However, the occurrence of type 2 failure after suture bridge repair remains a frequent problem because of the stress concentration and disturbance of tendon perfusion in the medial row. The authors have developed the H-loop knotless double-row repair (HLDR) to counteract these problems.To compare the biomechanical and histological outcomes of HLDR and KSBR for rotator cuff tear in the rabbit model.Controlled laboratory study.Acute bilateral supraspinatus tears were created on the shoulders of 46 New Zealand White rabbits. HLDR and KSBR were randomly performed on the left side or right side. Thirteen animals each were sacrificed at 2, 4, and 8 weeks after surgery (n = 39), with 6 rabbits used for histological evaluation and the other 7 rabbits for biomechanical testing. The remaining 7 animals from the original 46 were only used for initial biomechanical evaluation at week 0.Macroscopically, all repaired tendons were connected to their footprint on the greater tuberosity without postoperative complications at 8 weeks after surgery. The HLDR group had significantly better histological bone-to-tendon integration compared with the KSBR group in terms of fibrocartilage regeneration, collagen composition, and fiber organization. The biomechanical outcomes in the HLDR group were demonstrated to be better than those of the KSBR group at time 0 and 8 weeks after surgery.Both repair techniques were effective for rotator cuff tears in a rabbit rotator cuff tear model; however, HLDR demonstrated more advantages in improving biomechanical properties and histological tendon-to-bone healing compared with KSBR.This animal study suggested that HLDR might be an alternative choice for rotator cuff tears in humans to increase tendon-to-bone healing and reduce the rate of failure to heal.

Multiple studies have confirmed the pro-oncogenic effects of PAX3 in an array of cancers, but its role in prostate cancer (PCa) remains largely undefined. The aim of this study is to investigate the role of PAX3 in PCa. PAX3 expression was compared between PCa tumor tissue and nontumor tissues and PCa cell lines and normal prostate epithelial cells (PNT2) by western blot analysis and immunohistochemistry staining. MTT and immunofluorescence assays were used to detect PCa cell proliferation. Flow cytometry was used to evaluate cell apoptosis in PCa. Transwell assays were used for the determination of cell migration and PCa cell invasion. PAX3 expression was higher in PCa tissues and human PCa cell lines. Moreover, PAX3 silencing inhibited the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of PCa cells, and increased the rates of apoptosis. PAX3 silencing inhibited transforming growth factor-β (TGF-β)/Smad signaling in PCa cells. The effects of si-PAX3 on the proliferation, apoptosis, metastasis, and EMT of PCa cells were alleviated by TGF-β1 treatment. PAX3 silencing inhibits PCa progression through the inhibition of TGF-β/Smad signaling. This reveals PAX3 as a novel biomarker and therapeutic target for future PCa treatments.

Background Eosinophilic cystitis (EC) is a rare inflammatory disease characterized by the gathering and infiltration of numerous eosinophilia (EOS) in the bladder wall. Because of Few cases of EC have been reported globally, the epidemiology of EC is not well known. We report herein the details of one very scarce case of large tumor-like eosinophilic cystitis complicated with cystitis glandularis (CG) diagnosed by biopsy. Case presentation A 45-year-old Chinese man was referred to our hospital for the treatment of right lumbago and odynuria. Ultrasound examination indicated the low echo on the right portion wall and the neck of the bladder. Computed tomography showed a remarkable enhancing large mass that measured 5.0 cm × 2.3 cm located on the right portion of the bladder with undefined margin. For further treatment, diagnostic transurethral resection of the bladder was performed, the postoperative histopathological diagnosis was EC complicated with CG. After transurethral resection, antibiotics, glucocorticoids, and antihistamines were treated. The patient recovered uneventfully and was discharged on postoperative day 8 without evidence of recurrence followed-up for 6 months. Conclusion Large tumor-like eosinophilic cystitis complicated with cystitis glandularis is rare, malignant tumors need to be ruled out. We deem that prompt biopsy led to the exact diagnosis, appropriate treatment led to better prognosis.

Transcranial ultrasound stimulation (TUS) is a promising noninvasive brain stimulation technique with advantages of high spatial precision and ability to target deep brain regions. This study aimed to develop a TUS protocol to effectively induce brain plasticity in human subjects.An 80-second train of theta burst patterned TUS (tbTUS), regularly patterned TUS (rTUS) with the same sonication duration, and sham tbTUS was delivered to the motor cortex in healthy subjects. Transcranial magnetic stimulation (TMS) was used to examine changes in corticospinal excitability, intracortical inhibition and facilitation, and the site of plasticity induction. The effects of motor cortical tbTUS on a visuomotor task and the effects of occipital cortex tbTUS on motor cortical excitability were also tested.The tbTUS produced consistent increase in corticospinal excitability for at least 30 minutes, whereas rTUS and sham tbTUS produced no significant change. tbTUS decreased short-interval intracortical inhibition and increased intracortical facilitation. The effects of TMS in different current directions suggested that the site of the plastic changes was within the motor cortex. tbTUS to the occipital cortex did not change motor cortical excitability. Motor cortical tbTUS shortened movement time in a visuomotor task.tbTUS is a novel and efficient paradigm to induce cortical plasticity in humans. It has the potential to be developed for neuromodulation treatment for neurological and psychiatric disorders, and to advance neuroscience research. ANN NEUROL 2022;91:238-252.

To provide essential information of environmental triggers leading to CRD.We investigated the short-term effects of ambient air pollutants on CRD-related hospitalizations in people aged ≥ 65 years in Ningbo. Data on 23,610 cases of CRD requiring hospitalization were collected from January 2015 to August 2017. After adjusting for temporal trends, seasonality, meteorological conditions, day of week (DOW), and public holidays, we used generalized additive Poisson distribution models to calculate the excess risks (ERs) and 95% confidence intervals (95% CIs) of CRD related hospitalizations.Our results showed that fine particulate matter (PMIn conclusion, air pollution may have adverse effects on CRD-related hospitalizations among people aged ≥ 65 years in Ningbo. Therefore, public health measures should be taken to improve air quality.

Growing evidence suggests that both the medial prefrontal cortex (mPFC) and the subthalamic nucleus (STN) play crucial roles in conflict processing, but how these two structures coordinate their activities remains poorly understood. We simultaneously recorded electroencephalogram from the mPFC and local field potentials from the STN using deep brain stimulation electrodes in 13 Parkinson's disease patients while they performed a Stroop task. Both mPFC and STN showed significant increases in theta activities (2-8 Hz) in incongruent trials compared to the congruent trials. The theta activity in incongruent trials also demonstrated significantly increased phase synchronization between mPFC and STN. Furthermore, the amplitude of gamma oscillation was modulated by the phase of theta activity at the STN in incongruent trials. Such theta-gamma phase-amplitude coupling (PAC) was much stronger for incongruent trials with faster reaction times than those with slower reaction times. Elevated theta-gamma PAC in the STN provides a novel mechanism by which the STN may operationalize its proposed “hold-your-horses” role. The co-occurrence of mPFC-STN theta phase synchronization and STN theta-gamma PAC reflects a neural substrate for fronto-subthalamic communication during conflict processing. More broadly, it may be a general mechanism for neuronal interactions in the cortico-basal ganglia circuits via a combination of long-range, within-frequency phase synchronization and local cross-frequency PAC.

Magnetic Resonance (MR) imaging plays an important role in medical diagnosis and biomedical research. Due to the high in-slice resolution and low through-slice resolution nature of MR imaging, the usefulness of the reconstruction highly depends on the positioning of the slice group. Traditional clinical workflow relies on time-consuming manual adjustment that cannot be easily reproduced. Automation of this task can therefore bring important benefits in terms of accuracy, speed and reproducibility. Current auto-slice-positioning methods rely on automatically detected landmarks to derive the positioning, and previous studies suggest that a large, redundant set of landmarks are required to achieve robust results. However, a costly data curation procedure is needed to generate training labels for those landmarks, and the results can still be highly sensitive to landmark detection errors. More importantly, a set of anatomical landmark locations are not naturally produced during the standard clinical workflow, which makes online learning impossible. To address these limitations, we propose a novel framework for auto-slice-positioning that focuses on localizing the canonical planes within a 3D volume. The proposed framework consists of two major steps. A multi-resolution region proposal network is first used to extract a volume-of-interest, after which a V-net-like segmentation network is applied to segment the orientation planes. Importantly, our algorithm also includes a Performance Measurement Index as an indication of the algorithm's confidence. We evaluate the proposed framework on both knee and shoulder MR scans. Our method outperforms state-of-the-art automatic positioning algorithms in terms of accuracy and robustness.

Chemical messengers have been recognized as signaling molecules involved in regulating various physiological and metabolic activities. Nevertheless, they usually show limited regulatory efficiency due to the complexity of biological processes. Especially for tumor cells, antideath pathways and tumor metastasis are readily activated to resist chemical messenger regulation, further impairing antitumor outcomes. Therefore, it is imperative to develop strategies for tumor eradication with chemical messengers. Herein, a nanomessenger was prepared with signaling transduction cascades to amplify the regulatory activity of chemical messengers and mediate antitumor immunotherapy. Casup2+/supand Hsub2/subS as two chemical messengers were released from nanomessengers to synergistically elevate intracellular Casup2+/supstress and mediate subsequent cell death. Meanwhile, zinc protoporphyrin (ZnPP) as a messenger amplifier suppressed the antideath effect of tumor cells. As a result, tumor cells underwent Casup2+/sup-dependent cell deathivia/isignaling transduction cascades to release tumor-associated antigens, which further served as aniin situ/itumor vaccine to activate antitumor immunity.iIn vivo/istudies revealed that both primary tumors and distant metastases were markedly eradicated. Furthermore, immunological memory was fabricated to arrest tumor metastasis and recurrence. This work introduces cascade engineering into chemical messengers and thus offers a strategy for amplifying chemical messenger-mediated cellular regulation, which would promote the future development of chemical messenger-mediated immunotherapy.̀.

A hydrogel drug cargo based on 2D tungsten nitride nanosheets was fabricated. It exhibits stable NIR-II responsive photothermal properties and drug release behaviour. Moreover, this hydrogel shows excellent tumour ablation efficiency in vivo via NIR-II triggered multiple chemo/photothermal therapy.

Knee osteoarthritis (OA) is one of the most common musculoskeletal disorders. OA diagnosis is currently conducted by assessing symptoms and evaluating plain radiographs, but this process suffers from the subjectivity of doctors. In this study, we retrospectively compared five commonly used machine learning methods, especially the CNN network, to predict the real-world X-ray imaging data of knee joints from two different hospitals using Kellgren-Lawrence (K-L) grade of knee OA to help doctors choose proper auxiliary tools. Furthermore, we present attention maps of CNN to highlight the radiological features affecting the network decision. Such information makes the decision process transparent for practitioners, which builds better trust towards such automatic methods and, moreover, reduces the workload of clinicians, especially for remote areas without enough medical staff.

Background Osteosarcoma (OS) is the most common primary bone cancer in adolescents and lung metastasis is the leading cause of death in patients with OS. However, the molecular mechanisms that promote OS growth and metastasis remain unknown. Methods We investigated the expression of myosin light chain kinase family members between metastasis and non-metastasis patients in the TARGET database and ensured that only myosin light chain kinase family member 4 (MYLK4) had higher expression in metastatic osteosarcoma patients. Then we confirmed the results by immunohistochemistry (IHC) and Western blotting (WB) of OS tissues. The effect of MYLK4 on the metastasis and proliferation of OS cells was investigated by wound healing, Transwell and colony-formation assays. Mass spectrum analysis was used to ensure the new binding protein of MYLK4. Tissue microarrays analysis was used to show the correlation between MYLK4 and pEGFR (Y1068). A series of in vivo experiments were conducted to reveal the mechanisms by which MYLK4 modulated the metastasis and proliferation of OS. Results Myosin Light Chain Kinase Family Member 4 (MYLK4) was significantly upregulated in metastatic human OS tissues. Growth and metastasis of OS could be accelerated by MYLK4 overexpression, whereas silencing MYLK4 expression resulted in decreased cell growth and metastasis. Mechanistically, mass spectrum analysis showed that MYLK4 interacted with the epidermal growth factor receptor (EGFR) in osteosarcoma cells and promoted growth and metastasis via the EGFR signaling pathway. Tissue microarrays analysis also showed that MYLK4 expression had a positive correlation with the expression of pEGFR (Y1068). Moreover, the EGFR inhibitor gefitinib could partially reverse the effect of cell proliferation and metastasis caused by MYLK4 overexpression. Importantly, the combination of MYLK4 and EGFR inhibitors had synergistic effects on growth and metastasis of OS in vitro and in vivo. Conclusion Our results indicate that MYLK4 promotes OS growth and metastasis by activating the EGFR signaling pathway and can be a novel therapeutic target for the treatment of OS patients.

To evaluate the efficacy of combined pneumatic and enzymatic vitreolysis for treatment of severe cases of vitreomacular traction (VMT).We analyzed a retrospective, consecutive series of five patients diagnosed with severe VMT refractory to pneumatic vitreolysis who then received an additional ocriplasmin injection while their gas bubble from pneumatic vitreolysis was still present between February 2015 and February 2019. Vitreomacular traction release was confirmed using spectral-domain optical coherence tomography.Four of the five patients treated with combined pneumatic and enzymatic vitreolysis achieved VMT release by Day 28, and all cases eventually achieved complete VMT release. In addition to having VMT refractory to pneumatic vitreolysis, patient characteristics included broad adhesion diameter (1,500 µ m, n = 1), presence of epiretinal membrane (n = 2), age65 years (n = 4), and pseudophakia (n = 1). The visual acuity improved by three or more lines at 6 months in both of the patients with initial vision worse than 20/50 on an Early Treatment Diabetic Retinopathy Study chart but not in those whose vision was already fairly good (i.e., visual acuity20/60). None of the patients experienced the following complications after receiving this combined treatment: retinal tears or detachments, vitreous floaters, and ellipsoid zone changes.Sequential, combined pneumatic and enzymatic vitreolysis resulted in VMT release in all 5 cases (4 cases by 28 days) and may be a potentially useful alternative to surgical intervention for refractory VMT cases.

We investigated the effects of a relatively inexpensive, non-invasive, short-term treatment with low-dose normobaric hyperoxia (NBH) on macular edema in patients with retinal vein occlusion (RVO).Participants with macular edema associated with RVO were treated with 5 LPM of NBH via facemask (40% fraction of inspired oxygen, FIO2) for 3 h. Patients with non-fovea involving edema who elected to be observed returned for a second treatment 1 month later to test reproducibility.A 3-h session of NBH (n = 45) resulted in decreased maximum macular thickness (MMT) (mean 7.10%, tThree-hour treatment with 40% FIO2 NBH results in a significant reduction in MMT and CMT. This study supports an ischemic mechanism for macular edema associated with retinal vein occlusion.Short-term low-dose normobaric hyperoxia is a simple, inexpensive, and ubiquitous treatment that may provide an alternate or adjunctive approach to treating macular edema in patients who are resistant to or cannot afford anti-VEGF medications.

This study aimed to evaluate the impact of the echocardiographic parameter ratio E/E’ on the late recurrence of paroxysmal atrial fibrillation in patients after receiving radiofrequency catheter ablation. We retrospectively examined total of 288 paroxysmal atrial fibrillation (PAF) patients that underwent a preliminary radiofrequency catheter ablation (RFCA) in our hospital. During the first phase in this study, the patients were divided into 2 groups upon AF recurrence after RFCA: Recurrent group, n = 67 patients with rapid trial arrhythmia that lasted for more than 30 seconds at 3 months after RFCA and the Nonrecurrent group, n = 221. The clinical conditions were compared between the 2 groups. During the second phase of this study, based on the results in the first phase, the patients were divided into another 2 groups according to whether the ratio of E/E’ ≥13 .45: Higher ratio of E/E’ group, n = 55 and Lower ratio of E/E’ group n = 233. The late AF recurrent rates were also compared between the 2 groups. During the first phase, the univariate analysis indicated that the risk factors(P

Background. Amiodarone and propafenone are commonly used to maintain sinus rhythm in patients with atrial fibrillation (AF). However, it is not known which one is better in reducing early recurrence (ER) during the blanking period (the first three months after catheter ablation). Objective. To compare the efficacy and safety of amiodarone and propafenone in reducing ER during the blanking period after radiofrequency catheter ablation (RFCA) in AF patients. Materials and Methods. A total of 694 patients who underwent their first RFCA between May 2014 and May 2018 were enrolled in this retrospective study. Subsequently, 202 patients were excluded according to the exclusion criteria. The remaining 492 patients were divided into two groups based on the choice of antiarrhythmic drugs (AADs) (amiodarone or propafenone) in the blanking period. The primary outcomes were incidence of ER and AAD-associated adverse effects during the blanking period after RFCA. Propensity score matching (PSM) analyses were used to compare the outcomes of the two groups while controlling for confounders. Results. Among the 492 patients who took AADs in the blanking period (187 amiodarone and 305 propafenone), PSM selected 135 unique pairs of patients with similar characteristics. Amiodarone was associated with a lower ER incidence rate (23.7% versus 48.9%, p<0.001) and a similar rate of AAD-associated adverse effects (2.1% versus 1.5%, p=0.652). Treatment with amiodarone in the blanking period was significantly associated with a lower ER incidence rate compared to treatment with propafenone (HR=0.416, 95% CI 0.272–0.637, p<0.001). Conclusions. Compared with propafenone, amiodarone was associated with a lower ER incidence rate, and they had similar rates of AAD-associated adverse effects. Treatment with amiodarone in the blanking period was shown to be more effective in reducing ER than propafenone.

Prior expectations play an important role in the process of perception. In real life, facial expressions always appear within a scene, which enables individuals to generate predictions that affect facial expression judgments. In the present study, using event-related potentials, we investigated the influence of scene-based expectation on facial expression processing. In addition, we used a cognitive task to manipulate cognitive load to interfere with scene-based expectation. Results showed that under the condition of sufficient cognitive resources, faces elicited more negative N170 amplitudes and more positive N400 amplitudes when the emotional valence of the scenes and faces was congruent. However, in the condition of cognitive load, no such difference was observed. The findings suggested that the effect of expectation on facial expression recognition emerges during both the early and late stages of facial expression processing, and the effect is weakened when cognitive resources are occupied by unrelated tasks.

A benzothiazole-based turn-on fluorescent probe with a large Stokes shift (190nm) has been developed for hypochlorous acid detection. The probe displays prompt fluorescence response for HClO with excellent selectivity over other reactive oxygen species as well as a low detection limit of 0.08μM. The sensing mechanism involves the HClO-induced specific oxidation of oxime moiety of the probe to nitrile oxide, which was confirmed by HPLC-MS technique. Furthermore, imaging studies demonstrated that the probe is cell permeable and can be applied to detect HClO in living cells.

We reported an enzyme-free ELISA to detect breast cancer biomarker human epidermal growth factor receptor 2 (HER2) in human serum samples. Instead of enzymes (such as horseradish peroxidase) used in traditional ELISA, CuO nanoparticles were utilized as the signal probe. Compared to traditional enzymes, CuO nanoparticles have the advantages of low cost and good stability. After dissolving CuO nanoparticles with acid, the Cu (II) ions generated catalyzed the reaction of o-phenylenediamine with ascorbic acid to produce fluorescent quinoxaline derivative molecules. The immunoassay displays high sensitivity and good selectivity towards HER2 with detection limit as low as 9.65pg·mL-1. The assay was successfully applied to the analysis of HER2 in serum of breast cancer patients. The analysis results demonstrated the HER2 level in the serum samples determined by our assay were in good agreement with those determined by commercial HER2 ELISA kit. This enzyme-free ELISA assay can be easily adapted to the detection of other analytes. With these merits, the simple, sensitive and cost effective fluorescence immunoassay shows great potential for clinical applications.

Alterations in brain connectivity have been extensively reported in autism spectrum disorder (ASD), while their effects on the topology of brain network are still unclear. This study investigated whether and how the brain networks in children with ASD were abnormally organized with resting state EEG. Temporal synchronization analysis was first applied to capture the aberrant brain connectivity. Then brain network topology was characterized by three graph analysis methods including the commonly-used weighted and binary graph, as well as minimum spanning tree (MST). Whole brain connectivity in ASD group was found to be significantly reduced in theta and alpha band compared to typically development children (TD). Weighted graph found significantly decreased path length together with marginally significantly decreased clustering coefficient in ASD in alpha band, indicating a loss of small-world architecture to a random network. Such abnormal network topology was also demonstrated in the binary graph. In MST analysis, children with ASD showed a significant lower leaf fractions with a decrease trend of tree hierarchy in the alpha band, suggesting a shift towards line-like decentralized organization in ASD. The altered brain network may offer an insight into the underlying pathology of ASD and possibly serve as a biomarker that may aid in diagnosis of ASD.

We have developed a new DNA self-assembly amplification technology that generates electric current for electrochemical biosensing. The new technology was used for detection of human epidermal growth factor receptor 2 (HER2). In our technology, an aptamer was utilized both as a ligand for recognition and as a signal generating reporter. The aptasensor is based on a sandwich format and a DNA primer on a HER2 aptamer initiates auxiliary DNA self-assembled on the electrode to form a long one-dimensional DNA. The resulting DNA is then reacted with molybdate to generate electrochemical current. The sensitivity of the aptasensor with DNA self-assembly was greater than that of the aptasensor without DNA self-assembly due to the extended length of the DNA strand. Aptasensor analysis of HER2 in serum of breast cancer patients and healthy individuals is highly correlated (R2 = 0.9924) with ELISA measurements, with a p value of 1.37 × 10–7. The analysis of HER2 in serum (confirmed by ELISA) suggests that HER2 levels ...

Objective The study aimed to explore the modification to cortical oscillations of Parkinson disease (PD) patients by subthalamic nucleus deep brain stimulation (STN DBS). Methods With Magnetoencephalogram (MEG) detection, we examined the changes in absolute power spectrum of cortical oscillations in the PD patients with the treatment of STN DBS. Results The power analysis of PD patients showed a dominant over-synchronization of alpha and beta bands in temporal and occipital areas relative to the healthy control subjects. STN DBS on-state showed marked power increase in the gamma band of PD patients in the frontal and parietal relative to the DBS off-state. The alleviation of motor symptoms by STN DBS negatively correlated to the increase of high gamma oscillation in the right frontal cortex, and also correlated to the suppression of the alpha and beta oscillations in the right temporal cortex. Conclusion The treatment of STN DBS to PD patients might involve the augmentation of gamma activity and suppression of alpha and beta activities in cortical oscillations.

A multifunctional platform based on two-dimensional nanomaterials for combined antibacterial and anti-inflammatory therapy is developed. Bi2Se3 nanodiscs selectively eradicate Gram-positive bacteria with a low risk of drug resistance. Moreover, Bi2Se3 nanodiscs with antioxidant activity relieve intracellular oxidative stress of macrophages to suppress inflammation caused by bacterial infections.

Alzheimer's disease (AD) is the most common type of progressive neurodegenerative disorder, and is responsible for the most common form of dementia in the elderly. Inflammation occurs in the brains of patients with AD, and is critical for disease progression. In the present study, the effects of rapamycin (RAPA) on neuroinflammation lipopolysaccharide (LPS)-induced were investigated. SH‑SY5Y human neuroblastoma cells were treated with 20 µg/ml LPS and 0.1, 1 or 10 nmol/l RAPA, and were analyzed at various time points (6, 12 and 24 h). The mRNA expression levels of interleukin (IL) 1β, IL6 and hypoxia‑inducible factor 1α (HIF1α) were determined using reverse transcription‑quantitative polymerase chain reaction. The protein expression levels of phosphorylated (p‑)S6, p‑nuclear factor κB (NFκB), p‑inhibitor of NFκB kinase subunit β (IKKβ) and p‑tau protein were measured by western blot analysis. p‑IKKβ, p‑NFκB, p‑S6 and p‑tau were significantly decreased at 6, 12 and 24 h when cells were treated with ≥0.1 nmol/ml RAPA. In addition, female Sprague Dawley rats were intracranially injected with a single dose of 100 µg/kg LPS in the absence or presence of 1 mg/kg RAPA pretreatment. Brain tissues were subjected to immunohistochemical analysis 6‑24 h later, which revealed that the expression levels of HIF1α and p‑S6 in rat cerebral cortex were increased following LPS injection; however, this increase was abrogated by RAPA treatment. RAPA may therefore be considered a potential therapeutic agent for the early or emergency treatment of neuroinflammation.

Placental dysfunction and oxidative stress contribute to the pathogenesis of preeclampsia, which is a pregnancy-specific disorder. It has been suggested that the incidence of preeclampsia has a seasonal variation. Melatonin, as a seasonal factor, has been suggested to be involved in a successful pregnancy. In this study, we investigated the association of circulating levels of melatonin with preeclampsia. Serum was collected from women with preeclampsia (n=113) and gestation-matched healthy pregnant women, and the levels of melatonin were measured. In addition, the expression of melatonin receptors was examined in preeclamptic placentae (n=27). The association of the incidence of preeclampsia and seasonal variation was also analysed from 1491 women with preeclampsia within 77 745 healthy pregnancies. The serum levels of melatonin were significantly reduced in women with preeclampsia at presentation and these reduced serum levels of melatonin were not associated with the severity or time onset of preeclampsia nor with seasonal variation. The expression of melatonin receptor, MT1 was reduced in preeclamptic placentae. The incidence of preeclampsia was did exhibit seasonal variation, but this was largely due to the increase in the incidence of mild or late-onset preeclampsia. Our results demonstrate that reduced melatonin levels are associated with the development of preeclampsia but that the circulating levels of melatonin do not appear to be subject to seasonal variation during pregnancy.

Objectives. As a method of measuring the phase difference between 2 signals, the phase lag index (PLI) of the alpha and beta bands in patients with Parkinson’s disease (PD) was investigated by using magnetoencephalography (MEG). Methods. Eighteen PD patients were measured by MEG in the state of overnight withdrawal of levodopa and after levodopa treatment; meanwhile, Unified Parkinson’s Disease Rating Scale (UPDRS) III scale was evaluated. Results. Compared with healthy controls, alpha (8-13 Hz) PLI in the frontal and parietal areas elevated in PD patients, while the elevation was reversed by the levodopa treatment. The alterations of the UPDRS III total scale ( rs = 0.552, P = .013, n = 16) and the changes of akinesia scale ( rs = 0.622, P = .005, n = 16) were correlated to the change of beta (13-30 Hz) PLI in the left parietal area. The change of the UPDRS total scale was negatively correlated to duration of disease ( rs = 0.432, P = .047, n = 16). There was a negative correlation between the age of PD patients and the change of alpha PLI in the left frontal area ( rs = 0.519, P = .020, n = 16). Conclusions. PD patients showed a higher mu PLI in the sensorimotor area relative to the healthy controls. The improvement of motor symptoms of PD patients by levodopa was correlated to the inhibition of beta PLI in the sensorimotor area.

The authors describe a fluorometric method for the determination of the activity and inhibition of protein kinase A (PKA). In the presence of ATP, PKA catalyzes the transfer of phosphate groups from ATP to a peptide, and the generated phosphorylated peptide quenches the fluorescence (measured at excitation/emission peaks of 340/440 nm) of the hydroxyapatite nanoparticles (HAP-NPs). A linear logarithmic relationship of PKA concentrations with fluorescence intensity in the range from 1 to 50 U·L−1 was obtained, and the lower limit of detection (LOD) is 0.5 U·L−1. This is much lower than LODs reported in the literature. The PKA inhibitor H-89 was studied, and the inhibition plot has a sigmoidal shape with a half-maximal inhibitory concentration of around 750 nM of H-89. At a 4.5 nM level of H-89, fluorescence of HAP-NPs fell to levels of no PKA controls, demonstrating that the assay is a viable tool to screen for kinase inhibitors. An assay with Hela cell lysates in combination with forskolin (an activator of adenylyl cyclase) and IBMX (a phosphodiesterase inhibitor used to activate the cellular activity of PKA) resulted in decreased fluorescence of HAP-NPs. This suggests that the assay can be applied for testing in vitro cell kinase activity. In our perception, this method will enable high-throughput screening for kinase-related drugs and fluorometric enzymatic detection in various areas.

In this study, three types of galactosylated cholesterol (i.e., gal-PEG194-chol, gal-PEG1000-chol and gal-PEG2000-chol) were synthesized with one terminal of polyethylene glycol of various chain lengths conjugated to the galactoside moiety, and the other terminal conjugated to the cholesterol. The galactose-modified liposomes were prepared by thin film-hydration method and doxorubicin (DOX) was loaded to the liposomes by using a ammonium sulfate gradient procedure. The liposomal formulations with galactosylated cholesterol were characterized. Flow cytometry and laser confocal scanning microscopy analyses showed that the galactose-modified liposomes facilitated the intracellular uptake of liposomes into HepG2 via asialoglycoprotein receptor (ASGP-R) mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of galactose-modified liposomes was higher than that of the unmodified liposomes. Additionally, the study on frozen section of liver showed that the galactose-modified liposomes enhanced the intracellular uptake of liposomes into hepatocytes. Taken together, these results suggested that liposomes containing such galactosylated cholesterol (i.e., gal-PEG-chol), had a great potential as drug delivery carriers for hepatocyte-selective targeting.

Extensive studies have indicated brain function connectivity abnormalities in autism spectrum disorder (ASD). However, there is a lack of longitudinal or cross-sectional research focused on tracking age-related developmental trends of autistic children at an early stage of brain development or based on a relatively large sample. The present study examined brain network changes in a total of 186 children both with and without ASD from 3 to 11 years, an early and key development period when significant changes are expected. The study aimed to investigate possible abnormal connectivity patterns and topological properties of children with ASD from early childhood to late childhood by using resting-state electroencephalographic (EEG) data. The main findings of the study were as follows: (1) From the connectivity analysis, several inter-regional synchronizations with reduction were identified in the younger and older ASD groups, and several intra-regional synchronization increases were observed in the older ASD group. (2) From the graph analysis, a reduced clustering coefficient and enhanced mean shortest path length in specific frequencies was observed in children with ASD. (3) Results suggested an age-related decrease of the mean shortest path length in the delta and theta bands in TD children, whereas atypical age-related alteration was observed in the ASD group. In addition, graph measures were correlated with ASD symptom severity in the alpha band. These results demonstrate that abnormal neural communication is already present at the early stages of brain development in autistic children and this may be involved in the behavioral deficits associated with ASD.

Abnormalities in the development of placental vasculature in early pregnancy and the failure of transformation of the spiral arteries are associated with the pathogenesis of preeclampsia. Sex hormones influence neovascularisation during pregnancy. However the profiling of estrogen and progesterone in preeclampsia is controversial. In this study we investigated the serum levels of estrogen and progesterone in women with preeclampsia. Blood samples were collected from 86 preeclamptic and 97 gestation-matched normotensive pregnancies. The levels of 17β-estradiol (E2), progesterone and 2-methoxyestradiol (2-ME) in serum were measured. In addition, the levels of E2 and progesterone in conditioned media from preeclamptic or normotensive term placental explant cultures or placental explants that had been treated with hydrogen peroxide (H2O2) were measured. The expression of estrogen receptors (ER) and progesterone receptors (PR) in preeclamptic and control placentae were measured by immunohistochemistry. The serum levels of E2, progesterone and 2-ME were significantly reduced in women with preeclampsia compared to controls. There was no difference in the serum levels of E2 and progesterone between severe and mild or between early-onset and late-onset preeclampsia as well as between preeclampsia with and without fetal growth restriction (FGR). The levels of E2 and progesterone in preeclamptic placental explants cultures were significantly lower than in normotensive term placental explant cultures. Treatment with H2O2 was found to be associated with a reduction in E2 production by the placenta. We demonstrated lower levels of estrogen in preeclampsia and speculate that this reduction may be due to the impairment of placental function in preeclampsia.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children. Neuroimaging studies have revealed abnormalities of neural activities in some brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Recently, some investigators have demonstrated that nonlinear complexity analysis of neural activity may provide a new index to indicate ADHD. In the present study, we used the permutation entropy (PE) to measure the complexity of functional near-infrared spectroscopy (fNIRS) signals in children with and without ADHD during a working memory task, it was aimed to investigate the relationship between the PE values and the cortical activations, and the different PE values between the children with and without ADHD. We found that PE values exhibited significantly negative correlation with the cortical activations (r = −0.515, p = 0.003), and the PE values of right dorsolateral prefrontal cortex in ADHD children were significantly larger than those in normal controls (p = 0.027). In addition, the PE values of right dorsolateral prefrontal cortex were positively correlated to the ADHD index (r = 0.448, p = 0.012). These results suggest that complexity analysis of fNIRS signals could be a promising tool in diagnosing children with ADHD.

OBJECTIVE: To investigate the effect of androgen receptor (AR) on IgG protein expression and the proliferation and migration of prostate cancer cells. METHODS: Western blotting was used to detect the expression of AR protein and IgG in androgen-dependent prostate cancer LNCap cells and castration-resistant prostate cancer PC-3 cells. In AR-overexpressing cells (PC-3-AR cells) established by transfecting PC-3 with AR gene (pCDNA3.1) and LNCap cells with small interfering RNA-mediated AR silencing (LNCap-siAR cells) were analyzed for expressions of AR protein and IgG with Western blotting; the expression of IgG mRNA was detected by Q-PCR, and the cell proliferation and migration were assessed with MTT assay and wound healing assay, respectively. RESULTS: Compared with PC-3 cells, LNCap cells expressed a higher level of AR protein and a lower level of IgG (P < 0.05). PC-3-AR cells showed attenuated proliferation and migration with a lowered expression of IgG (P < 0.01), while LNCap-siAR cells showed enhanced proliferation and migration with increased expression of IgG (P < 0.01). CONCLUSION: The expression of AR is inversely correlated with IgG and is associated with the proliferation and migration of prostate cancer cells in vitro.

To enhance the solubility and improve the bioavailability of hydrophobic curcumin, a new kind of imprinted-like biopolymeric micelles (IBMs) was designed. The IBMs were prepared via co-assembly of gelatin-dextran conjugates with hydrophilic tea polyphenol, then crosslinking the assembled micelles and finally removing the template tea polyphenol by dialysis. The obtained IBMs show selective binding for polyphenol analogous drugs over other drugs. Furthermore, curcumin can be effectively encapsulated into the IBMs with 5×10(4)-fold enhancement of aqueous solubility. We observed the sustained drug release behavior from the curcumin-loaded IBMs (CUR@IBMs) in typical biological buffers. In addition, we found the cell uptake of CUR@IBMs is much higher than that of free curcumin. The cell cytotoxicity results illustrated that CUR@IBMs can improve the growth inhibition of HeLa cells compared with free curcumin, while the blank IBMs have little cytotoxicity. The in vivo animal study demonstrated that the IBMs could significantly improve the oral bioavailability of curcumin.

Breast cancer is the most common cancer in women worldwide. In this study, we evaluate the potential risk factors for lymph node metastasis in invasive breast cancer patients with axillary dissection. 147 patients were included into this prospective study. The prognostic biomarkers including Ki-67, human epidermal growth factor receptor 2 (HER-2), hormone receptor status, p53, and lymph node involvement were determined by immunohistochemistry. The association between lymph node metastasis and these biomarkers was analyzed. Lymph node metastasis was found in 62 patients out of 147 patients. The high levels of Ki-67 positive (greater than 20 %) were positively correlated with a higher incidence of lymph node metastasis, including the numbers of lymph nodes that contain tumor cells and the lymph node metastatic rate. The high rate of positive lymphovascular invasion (LVI) is associated with lymph node metastasis. However, the levels of Ki-67 positive were not correlated with the positive rate of LVI. There was also no association between lymph node metastasis and other prognostic biomarkers, such as HER-2, estrogen receptor, progesterone receptor, and p53. In addition, apart from p53, the levels of Ki-67 positive were correlated with other prognostic biomarkers. Our data suggest that Ki-67 positivity has value as a prognostic and predictive biomarker in breast cancer and may be a valuable proliferation marker in routine diagnosis of breast cancer.

The involvement of hormonal factors in developing endometrial cancer is well documented. In particular, excess or unopposed estrogen is a major risk factor. Endometrial cancer is divided into estrogen-dependent and estrogen-independent types. Studies suggested that the subtypes of endometrial cancer share many common risk factors. Whether the levels of sex hormones differ between types 1 and 2 endometrial cancer has not been investigated. In this study, levels of estrogen, progesterone, testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were investigated between type 1 and type 2 endometrial cancer taking into account menopausal status and parity. The sex hormones levels and estrogen and progesterone receptors were measured in 187 women with endometrial cancer. The levels of estradiol (E2), progesterone, testosterone, FSH and LH were not different between the subtypes of endometrial cancer regardless of menopausal status. In addition, the sex hormones were not different between patients of different party regardless of the menopausal status. The majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive. Our data suggest that type 2 endometrial cancer is not completely estrogen independent, and type 1 and type 2 endometrial cancers may have a similar pathogenesis.

Nine biflavonoids (1–9) were isolated from ethanolic extract of Selaginella uncinata (Desv.) Spring. Their structures were determined by spectra analysis. Compounds 1–9 were classified into four types according to the connection styles of the two flavonoid parts. Among them, 1 was elucidated as a new compound, while 4 was one with a new configuration. All isolates exhibited inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) in an enzyme assay with IC50 values ranging from 4.6 to 16.1 μM, and the relationship between the structures and activities was discussed. Docking simulations of these compounds demonstrated they had tight binding capacities towards the allosteric site of PTP1B. Additionally, the glucose uptake activities of 1–9 were evaluated in insulin-resistant HepG2 cells, while the effect of 1 on the activation of IRS-1/PI3K/Akt pathway was revealed by Western Blot analysis.

The purpose of this study was to investigate the long-term effects of laparoscopic splenectomy (LS) for patients with chronic immune thrombocytopenia (ITP), and to identify predictive factors for promising hematological outcomes. We retrospectively analyzed the clinical records and follow-up data in patients who underwent LS for chronic ITP from November 2005 to August 2012. The related parameters were assessed by univariate and multivariate logistic regression analyses. The curve of life table was drawn to clarify the long-term response rate. Of the 92 included patients, 49 (53.3 %) patients achieved a complete response, 21 patients (22.8 %) a partial response, and the remaining 22 (23.9 %) showed no response to LS. Eleven patients relapsed within 1 year after LS, especially within 3 months (n = 7), while three patients relapsed 17, 26, and 28 months after LS, respectively. Long-term specific complications after LS were not observed. Platelet counts on postoperative month 3 (POM 3) is a significant independent predictor of long-term favorable hematological outcomes (P < 0.001). Based on our study, we conclude that LS is associated with promising long-term response for patients with chronic ITP, and platelet counts on POM 3 could be used as a predictor of long-term hematological outcome.

To evaluate the different traits of mesenchymal stem cell (MSC) isolated from osteosarcoma (OS) and normal bone marrow (BM) induced by bone-morphogenetic protein-2 (BMP-2). MSCs from implanted osteosarcoma or femur bone marrow were isolated and cultured. Differentiation potency was verified and phenotypes were evaluated by flow cytometry. Increased or decreased expressions of BMP-2 were delivered by adenovirus and lentivirus vector, respectively. Expressions of VEGF, EMMPRIN, and MMP-9 were examined. Cell cycle, apoptosis, invasiveness, and proliferation assays were performed between the transfected groups and controls. Increased BMP-2 induced over-expression of VEGF, EMMPRIN, and MMP-9 in OS- and BM-MSCs both intra- and extra-cellularly. Decreased BMP-2 expression induced inhibition of the factors. Increased BMP-2 also induced less population of cells at G1 phase, more apoptotic cells, more cells that invade through Transwell membrane, and faster proliferation in OSMSC compared to those in BMMSC. BMP-2 induced higher expression of tumorigenic factors, which could be responsible for promoting the proliferation and aggressiveness of OSMSC over BMMSC.

Objective When prefrontal-transcranial magnetic stimulation (p-TMS) performed, it may evoke hybrid artifact mixed with muscle activity and blink activity in EEG recordings. Reducing this kind of hybrid artifact challenges the traditional preprocessing methods. We aim to explore method for the p-TMS evoked hybrid artifact removal. Approach We propose a novel method used as independent component analysis (ICA) post processing to reduce the p-TMS evoked hybrid artifact. Ensemble empirical mode decomposition (EEMD) was used to decompose signal into multi-components, then the components were separated with artifact reduced by blind source separation (BSS) method. Three standard BSS methods, ICA, independent vector analysis, and canonical correlation analysis (CCA) were tested. Main results Synthetic results showed that EEMD-CCA outperformed others as ICA post processing step in hybrid artifacts reduction. Its superiority was clearer when signal to noise ratio (SNR) was lower. In application to real experiment, SNR can be significantly increased and the p-TMS evoked potential could be recovered from hybrid artifact contaminated signal. Our proposed method can effectively reduce the p-TMS evoked hybrid artifacts. Significance Our proposed method may facilitate future prefrontal TMS-EEG researches.

A black phosphorus (BP)-based drug delivery system for synergistic photodynamic/photothermal/chemotherapy of cancer is constructed. As a 2D nanosheet, BP shows super high drug loading capacity and pH-/photoresponsive drug release. The intrinsic photothermal and photodynamic effects of BP enhance the antitumor activities. The synergistic photodynamic/photothermal/chemotherapy makes BP-based drug delivery system a multifunctional nanomedicine platform.

POEMS syndrome is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. Bortezomib is an important component of the chemotherapy regimen associated with multiple myeloma, and has been previously applied to POEMS syndrome. We present a 56-year-old Chinese man who was given subcutaneous administration of bortezomib as part of the BDex (bortezomib–dexamethasone) regimen for his POEMS syndrome. The peripheral neuropathy and laboratory-test results of the patient improved dramatically with 4 cycles of treatment, resulting in a complete response. In addition, the treatment was well tolerated and adequate peripheral blood hematopoietic stem cells were collected for an ensuing autologous stem cell transplant.

To evaluate the safety and efficacy of laparoscopy-assisted distal gastrectomy (LADG) in patients with early gastric cancer (EGC) to determine whether LADG is an acceptable alternative to open distal gastrectomy (ODG).LADG combined with less than D2 or D2 lymphadenectomy for EGC is still a controversial surgical intervention for its uncertain oncological safety and economic benefit. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) and non-RCTs of LADG versus ODG to evaluate whether the safety and efficacy of LADG in patients with EGC are equivalent to those of ODG.A comprehensive search of PubMed, EMBASE, Cochrane Library, and China Knowledge Resource Integrated Database was performed. Eligible trials published between January 1, 1994, and December 31, 2010, were included in the study. Data synthesis and statistical analysis were carried out by RevMan 5.0 software. The quality of evidence was assessed by GRADEpro 3.2.2.Twenty-two studies with 3411 participants were included in this study. The mean number of lymph nodes retrieved in LADG was close to that retrieved in ODG (in the less than D2 resection: weighted mean difference [WMD] = -1.79; 95% confidence interval [95% CI], -5.78 to 2.19; P = 0.38; heterogeneity: P0.00001, I = 98%; and in the D2 resection: WMD = -1.53; 95% CI, -3.56 to 0.51; P = 0.14; heterogeneity: P = 0.23, I = 26%). The overall postoperative morbidity was significantly less in LADG than in ODG (relative risk = 0.58; 95% CI, 0.46-0.74; P0.00001; heterogeneity: P = 0.94, I = 0%). LADG reduced the intraoperative blood loss, postoperative analgesic consumption, and hospital duration, without increasing the total hospitalization costs and cancer recurrence rate. The long-term survival rate of patients undergoing LADG was similar to that of patients undergoing ODG. However, LADG was still a technically dependent and time-consuming procedure. Conversion rate of LADG was 0% to 2.94%. The reported reasons for conversion were bleeding, adhesion, and safety resection margin requirement.: There were potential biases and significant heterogeneity in some clinical outcome measures in this study. Methodologically high-quality controlled clinical trials were sparse for this new surgical intervention. According to The Grading of Recommendations Assessment, Development and Evaluation approach, when assessing the safety and efficacy of LADG by comparing with those of ODG with the defined clinical outcomes in patients with EGC, the quality of the currently available clinical evidence was very low.LADG may be a technically feasible alternative for EGC when it is performed in experienced surgical centers in which patients undergoing LADG may benefit from the faster postoperative recovery. However, the currently available evidence cannot exclude the potential clinical benefits or harms, especially in the node-positive cases. Methodologically high-quality comparative studies are needed for further evaluation.

The purpose of this study is to investigate brain metabolic changes in patients with amnestic mild cognitive impairment (aMCI) using multivoxel proton MR spectroscopy ((1)H-MVS).Fourteen aMCI patients and fifteen healthy control subjects participated in this experiment. All MR measurements were acquired using a 1.5-T GE scanner. (1)H-MVS point resolved spectroscopy (2D PROBE-CSI PRESS) pulse sequence (TE = 35 ms; TR = 1,500 ms; phase × frequency, 18 × 18) was used for acquiring MRS data. All data were post-processed using Spectroscopy Analysis by General Electric software and linear combination of model (LCModel). The absolute concentrations of N-acetylaspartate (NAA), choline (Cho), myoinositol (MI), creatine (Cr), and the metabolite ratios of NAA/Cr, Cho/Cr, MI/Cr, and NAA/MI were measured bilaterally in the posterior cingulate gyrus (PCG), inferior precuneus (Pr), paratrigonal white matter (PWM), dorsal thalamus (DT), and lentiform nucleus (LN).Patients with aMCI displayed significantly lower NAA levels in the bilateral PCG (p 0.01), PWM (p 0.05), and left inferior Pr (p 0.05). The metabolite ratio of NAA/MI was decreased in the bilateral PCG (p 0.01) and PWM (p 0.05) and in the left DT (p 0.01). NAA/Cr was decreased in the left PCG (p 0.01), DT (p 0.05), right PWM (p 0.05), and LN (p 0.05). However, MI/Cr was elevated in the right PCG (p 0.01) and left PWM (p 0.05). Significantly increased Cho level was also evident in the left PWM (p 0.05).Our observations of decreased NAA, NAA/Cr, and NAA/MI, in parallel with increased Cho and MI/Cr might be characteristic of aMCI patients.

The technique of stent-assisted coil embolization has been widely used in the clinic, while its efficacy and safety have yet to be evaluated. This study investigates the values of computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) in evaluating the Enterprise stent-assisted coil embolization in the treatment of intracranial wide-necked aneurysm.A total of 578 intracranial wide-necked aneurysm patients confirmed by MRA + CTA + DSA examinations were included and treated with Enterprise stent-assisted coil embolization in this study. All patients were assigned into complete embolization (CE) group and incomplete embolization (IE) group according to the results of postoperative MRA + CTA + DSA examinations and Raymond grades. Hunt-Hess grades, incidence of complication and Glasgow Outcome Scale (GOS) grades of patients were investigated to assess the therapeutic effect of Enterprise stent-assisted coil embolization in intracranial wide-necked treatment. Multivariate logistic regression analysis was performed to assess risk factors for the therapeutic effect of Enterprise stent-assisted coil embolization in intracranial wide-necked aneurysm.CTA images offered a better and clearer view than MRA and DSA images in both the CE and IE groups. Both the sensitivity and specificity of CTA were apparently higher than those of MRA. Patients in the CE group enjoyed a higher good GOS rate but a lower incidence of complication than those in the IE group. In Enterprise stent-assisted coil embolization treatment, the Hunt-Hess grade, hypertension, and size of artery aneurysm were independent factors affecting the therapeutic effect of Enterprise stent-assisted coil embolization in intracranial wide-necked aneurysm.Compared with MRA, CTA shows a higher value in evaluating the therapeutic effect of Enterprise stent-assisted coil embolization for the treatment of intracranial wide-necked aneurysm, and can thus serve as an important means of predicting the therapeutic effect of endovascular intervention in treating patients with intracranial wide-necked aneurysm.

Fluorescence imaging of nitric oxide (NO) in vitro and in vivo is essential to developing our understanding of the role of nitric oxide in biology and medicine. Current probes such as diaminofluorescein depend on reactions with oxidized NO products, but not with nitric oxide directly, and this limits their applicability. Here we report the formation of an imaging probe for nitric oxide by coordinating the highly fluorescent chemical 4-methoxy-2-(1H-naphtho[2,3-d]imidazol-2-yl)phenol (MNIP) with Cu(II). The coordination compound MNIP-Cu reacts rapidly and specifically with nitric oxide to generate a product with blue fluorescence that can be used in vitro and in vivo. In the present study MNIP-Cu was used to reveal nitric oxide produced by inducible nitric oxide synthase in lipopolysaccharide (LPS)-activated macrophages (Raw 264.7 cells) and by endothelial nitric oxide synthase in endothelial cells (HUVEC). MNIP-Cu was also used to evaluate the distribution of nitric oxide synthesis in a model of acute liver injury induced by LPS and d-galactosamine in mice. The results demonstrate that MNIP-Cu can act as a novel fluorescent probe for nitric oxide and has many potential applications in biomedical research.

Mina Yan,1,2 Zhaoguo Zhang,2 Shengmiao Cui,3 Ming Lei,2 Ke Zeng,2 Yunhui Liao,2 Weijing Chu,2 Yihui Deng,1 Chunshun Zhao2 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2SchoolofPharmaceutical Sciences, SunYat-sen University, 3Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China Abstract: Layered double hydroxide (LDH) has attracted considerable attention as a drug carrier. However, because of its poor in vivo behavior, polyethylene glycolylated (PEGylated) phospholipid must be used as a coformer to produce self-assembled core–shell nanoparticles. Inthe present study, we prepared a PEGylated phospholipid-coated LDH (PLDH) (PEG-PLDH) delivery system. The PEG-PLDH nanoparticles had an average size of 133.2 nm. Their core–shell structure was confirmed by transmission electron microscopy and X-ray photoelectron spectroscopy. In vitro liposome-cell-association and cytotoxicity experiments demonstrated its ability to be internalized by cells. In vivo studies showed that PEGylated phospholipid membranes greatly reduced the blood clearance rate of LDH nanoparticles. PEG-PLDH nanoparticles demonstrated a good control of tumor growth and increased the survival rate of mice. These results suggest that PEG-PLDH nanoparticles can be a useful drug delivery system for cancer therapy. Keywords: lipid membrane, positive charge, delivery system, cancer therapy

This study was designed to evaluate the analgesic effect of wrist-ankle acupuncture (WAA) for patients with primary liver cancer (PLC) after transcatheter arterial chemoembolization (TACE). Sixty PLC patients with post-TACE visual analog pain intensity scores greater than 3 were divided equally into two groups receiving either WAA or oral morphine sulphate (MOR) for post-TACE pain. Pain intensity scores were reassessed at 1, 2, 4, and 6 h after analgesic intervention. Patients were also monitored for adverse reactions to analgesic treatment. Pain scores recorded when the patients first felt pain after TACE showed no statistical difference between the two groups (p > 0.05). WAA and MOR had indistinguishable degrees of pain relief 1, 2, and 4 h after analgesic intervention (p > 0.05). At 6 h after intervention, the WAA group experienced significantly greater pain relief than the MOR group (p < 0.05). Incidence of abdominal distension was lower in the WAA group than in the MOR group (p < 0.05). The results suggest that WAA not only had an analgesic effect equal to or greater than MOR in PLC patients with moderate to severe post-TACE pain, but also reduced the incidence of post-operative abdominal distention.