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Atrial fibrillation (AF) is the most common persistent arrhythmia and is likely to cause strokes and damage to heart function in patients. Electrocardiogram (ECG) is the gold standard for detecting AF. However, ECGs have short boards with short monitoring cycles and problems with gathering. It is also difficult to detect a burst AF through ECG. In contrast, photoplethysmography (PPG) is easy to perform and suitable for long-term monitoring. In this study, we propose a method that combines time-frequency analysis with deep learning and identifies AF based on PPG. The advantage of the method is that there is no need for the noise filtering and feature extraction of PPG, and it has a high generalization capability. The data for the experiment came from three publicly accessible databases. The first part of the experimental method uses data augmentation to convert the 10 s PPG segment into a time-frequency chromatograph by means of time-frequency analysis. The second part inputs the chromatograph into a hybrid framework that combines a convolutional neural network (CNN) and long short-term memory (LSTM) for AF/nonAF classification. The experimental results show that the method has a high classification accuracy, sensitivity, specificity, and F1 score, which are equal to 98.21%, 98.00%, 98.07% and 98.13%, respectively. The area under the receiver operating characteristic curve (AUC) is 0.9959. The model we propose not only aids doctors in diagnosing AF but also provides a method for identifying AF through portable wearable devices.

Introduction: The self-adhesive mesh has become increasingly popular since its launch and has been proven to be reliable in laparoscopic hernia reparation. However, self-adhesive mesh may ...

Objective: Increasing evidence emphasizes the clinical implications of RNA binding proteins (RBPs) in cancers. This study aimed to develop a RBP signature for predicting prognosis in glioma.Methods: Two glioma datasets as training (n = 693) and validation (n = 325) sets were retrieved from the CGGA database. In the training set, univariate Cox regression analysis was conducted to screen prognosis-related RBPs based on differentially expressed RBPs between WHO grade II and IV. A ten-RBP signature was then established. The predictive efficacy was evaluated by ROCs. The applicability was verified in the validation set. The pathways involving the risk scores were analyzed by ssGSEA. scRNA-seq was utilized for evaluating their expression in different glioma cell types. Moreover, their expression was externally validated between glioma and control samples.Results: Based on 39 prognosis-related RBPs, a ten RBP signature was constructed. High risk score distinctly indicated a poorer prognosis than low risk score. AUCs were separately 0.838 and 0.822 in the training and validation sets, suggesting its well performance for prognosis prediction. Following adjustment of other clinicopathological characteristics, the signature was an independent risk factor. Various cancer-related pathways were significantly activated in samples with high risk score. The scRNA-seq identified that risk RBPs were mainly expressed in glioma malignant cells. Their high expression was also found in glioma than control samples.Conclusion: This study developed a novel RBP signature for robustly predicting prognosis of glioma following multi-data set verification. These RBPs may affect the progression of glioma.

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p

Oculomotor nerve palsy (ONP) caused by posterior communicating aneurysm (PcomAA) is mainly treated by surgical clipping or endovascular coiling. However, there are still some controversies about which treatment method could provide the more beneficial prognosis. This study aimed to compare ONP recovery rate between surgical clipping and endovascular coiling in patients diagnosed as PcomAA combined with ONP, and explore the potential risk factors of ONP recovery. The clinical data of 152 patients with ONP caused by PcomAA were retrospectively analyzed. Diameter of aneurysm, different treatment methods (surgical clipping or endovascular coiling), subarachnoid hemorrhage (SAH), degree of preoperative ONP, time from ONP onset to treatment, as well as degree of ONP symptom recovery were collected from medical records. All patients were followed up for at least 1 year. One hundred twelve patients underwent surgical clipping and 40 patients received endovascular coiling. There were no significant differences in age, gender, aneurysm diameter, hypertension, dyslipidemia, time from ONP symptom onset to treatment, SAH, and preoperative ONP degree between the 2 groups (all P > .05). Time to complete or partial recovery was 86.7 ± 35.7 days for patients receiving surgical clipping and 132.6 ± 37.5 days for patients receiving endovascular coiling, respectively (Log rank test, P

Ferroptosis is an iron-dependent form of cell death characterized by the accumulation of intracellular lipid reactive oxygen species (ROS). Ferroptosis is significantly different from other types of cell death including apoptosis, autophagy, and necrosis, both in morphology and biochemical characteristics. The mechanisms that are associated with ferroptosis include iron metabolism, lipid oxidation, and other pathophysiological changes. Ferroptosis inducers or inhibitors can influence its occurrence through different pathways. Ferroptosis was initially discovered in tumors, though recent studies have confirmed that it is also closely related to a variety of neurological diseases including neurodegenerative disease [Alzheimer’s disease (AD), Parkinson’s disease (PD), etc.] and stroke. This article reviews the definition and characteristics of ferroptosis, the potential mechanisms associated with its development, inducers/inhibitors, and its role in non-neoplastic neurological diseases. We hope to provide a theoretical basis and novel treatment strategies for the treatment of central nervous system diseases by targeting ferroptosis.

Marital status proved to be an independent prognostic factor for survival in patients with breast cancer. We therefore strove to explore the impact of dynamic changes in marital status on the prognosis of breast cancer patients. We selected patients meeting the eligibility criteria from the Surveillance, Epidemiology, and End Results cancer database. We then used multivariate Cox proportional hazard regression model to analyze the effect of dynamic changes in marital status on the prognosis of overall survival (OS) and breast cancer-specific special survival (BCSS). Compared with the patients in the Single–Single group and the divorced/separated/widowed–divorced/separated/widowed (DSW–DSW) group, patients in the Married–Married group were significantly associated with better BCSS (HR 1.13, 95% CI: 1.03–1.19, P P P P P = 0.660; HR 1.06, 95% CI: 0.97–1.15, P = 0.193, respectively) but better OS (HR 1.14, 95% CI: 1.09–1.19, P P P = 0.003) but no difference in OS (HR 1.08, 95% CI: 0.98–1.18, P = 0.102); In contrast to the Married–DSW group, the Married–Married group exhibited better BCSS (HR 1.11, 95% CI: 1.05–1.18, P P

Objectives N6‐methyladenosine (m6A) is a ubiquitous epigenetic RNA modification that plays a pivotal role in tumour development and metastasis. In this study, we aimed to investigate the expression profiling, clinical significance, biological function and the regulation of m6A‐related genes in hepatoblastoma (HB). Materials and Methods The mRNA and protein expression levels of m6A‐related genes were analysed using Gene Expression Omnibus (GEO) and tissue microarray (TMA) cohort. Kaplan‐Meier analysis was performed to evaluate the prognostic value of m6A‐related genes in HB. Knockdown of m6A‐related genes was conducted to analyse its function on cell proliferation, migration and invasion. Furthermore, bioinformatics analysis and experimental verification were used to explore the potential molecular mechanism and signalling pathway. Results We found that most m6A‐related genes were significantly upregulated in HB tumour tissues. High levels of methyltransferase‐like 3 (METTL3, P = .013), YTHDF2 (P = .037) and FTO (P = .032) indicated poor clinical outcomes, and the upregulation of METTL3 was an independent prognostic factor in HB patients. Functional assays showed that knockdown of METTL3 could dramatically suppress the proliferation, migration and invasion of HB cells. In addition, METTL3 was identified to be a direct target of microRNA‐186 (miR‐186). Consistently, miR‐186 was low expressed in HB tumour tissues. Moreover, overexpression of miR‐186 significantly inhibited cell aggressive phenotype both in vitro and in vivo, while the inhibitory effect could be reversed by METTL3 overexpression. Mechanism study indicated that miR‐186/METTL3 axis contributed to the progression of HB via the Wnt/β‐catenin signalling pathway. Conclusions M6A‐related genes were frequently dysregulated in HB. miR‐186/METTL3/Wnt/β‐catenin axis might serve as novel therapeutic targets and prognostic biomarkers in HB.

Hepatoblastoma (HB) is the most common and aggressive malignant hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Recently, long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) has been reported to be an oncogenic gene in multiple cancers. However, the expression status and specific role of ZFAS1 involved in cancer progression of human HB remain unknown. This study aimed to identify the role of ZFAS1/miR-193a-3p/RALY axis in the development of HB. Here we showed that the expression of ZFAS1 was significantly upregulated in both HB tissues and cell lines. High ZFAS1 expression was significantly associated with aggressive tumor phenotypes and poorer overall survival in HB. In vitro and in vivo function assays indicated that silencing of ZFAS1 significantly suppressed HB cell proliferation and invasion. Furthermore, miR-193a-3p was identified to be the target of ZFAS1. Subsequently, RALY was confirmed to be regulated by miR-193a-3p/ZFAS1 axis. Mechanistically, our results indicated that the ZFAS1 participated to the progression of HB via regulating the HGF/c-Met signaling. Collectively, these data demonstrated that ZFAS1 acted as an oncogene to promote initiation and progression of HB by regulating miR-193a-3p/RALY (RALY Heterogeneous Nuclear Ribonucleoprotein) axis via HGF/c-Met Pathway, which provides an efficient marker and new therapeutic target for HB.

The mutation of B-RafV600E is widespread in a variety of human cancers. Its inhibitors vemurafenib and dabrafenib have been launched as drugs for treating unresectable melanoma, demonstrating that B-RafV600E is an ideal drug target. This study focused on developing novel B-RafV600E inhibitors as drug leads against various cancers with B-RafV600E mutation. Using molecular modeling approaches, 200 blockbuster drugs were spliced to generate 283 fragments followed by molecular docking to identify potent fragments. Molecular structures of potential inhibitors of B-RafV600E were then obtained by fragment reassembly followed by docking to predict the bioactivity of the reassembled molecules. The structures with high predicted bioactivity were synthesized, followed by in vitro study to identify potent B-RafV600E inhibitors. A highly potent fragment binding to the hinge area of B-RafV600E was identified via a docking-based structural splicing approach. Using the fragment, 14 novel structures were designed by structural reassembly, two of which were predicted to be as strong as marketed B-RafV600E inhibitors. Biological evaluation revealed that compound 1m is a potent B-RafV600E inhibitor with an IC50 value of 0.05 μmol/L, which was lower than that of vemurafenib (0.13 μmol/L). Moreover, the selectivity of 1m against B-RafWT was enhanced compared with vemurafenib. In addition, 1m exhibits desirable solubility, bioavailability and metabolic stability in in vitro assays. Thus, a highly potent and selective B-RafV600E inhibitor was designed via a docking-based structural splicing and reassembly strategy and was validated by medicinal synthesis and biological evaluation.

Hepatoblastoma (HB) is the most common hepatic neoplasm in childhood and the therapeutic outcomes remain undesirable due to its recurrence and metastasis. Increasing evidence shows that dipeptidase 1 (DPEP1) has pivotal function in tumorigenesis in multiple tumors. However, the expression pattern, biological function, and underlying mechanism of DPEP1 in HB have not been reported. Here we showed that DPEP1 was significantly upregulated and was associated with poor prognosis in HB patients. In vitro and in vivo assays indicated that silencing DPEP1 significantly suppressed HB cell proliferation, migration, and invasion, while DPEP1 overexpression exhibited the opposite effect. In addition, we identified that DPEP1 was a direct target of microRNA-193a-5p (miR-193a-5p). Functional experiments demonstrated that overexpression of miR-193a-5p significantly inhibited cell proliferation and invasion of HB cells, while the inhibitory effect could be reversed by DPEP1 overexpression. Moreover, miR-193a-5p was decreased in HB tumor tissues and associated with a poor clinical prognosis. Mechanistically, our results indicated that the miR-193a-5p/DPEP1 axis participated to the progression of HB via regulating the PI3K/Akt/mTOR (phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin) signaling. In conclusion, our findings suggest that the miR-193a-5p /DPEP1 axis might be a good prognostic predictor and therapeutic target in HB.

The role of primary tumor surgery in the management of differentiated thyroid cancer (DTC) with distant metastases (DM) remains controversial. We aimed to explore the survival benefit of primary tumor surgery in patients with different metastatic sites. A retrospective cohort study based on the SEER database was conducted to identify DTC patients with DM diagnosed between 2010 and 2016. Patients were divided into following 2 groups: surgery and non-surgery group. Propensity score weighting was employed to balance clinicopathologic factors between the 2 groups. Of 3537 DTC patients with DM, 956 (66.0%) patients underwent primary tumor surgery while 493 (34.0%) patients did not. There were 798 all-cause deaths and 704 DTC-specific deaths over a median follow-up of 22 months. The weighted 3-year overall survival (OS) for the surgery group was 55.2%, compared to 27.8% (P

Glioblastoma is a malignant brain tumor originating in the central nervous system. Successfully therapy of this disease required the efficient delivery of therapeutic agents to the tumor cells and tissues. Delivery of anticancer drugs using novel nanocarriers is promising in glioma treatment.Polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) were constructed for the delivery of temozolomide (TMZ). The anti-tumor effects of the three kinds of nanocarriers were compared to provide the optimum choice for gliomatosis cerebri treatment.TMZ-loaded PNPs (T-PNPs), SLNs (T-SLNs), and NLCs (T-NLCs) were formulated. Their particle size, zeta potential, drug encapsulation efficiency (EE), and drug loading (DL) capacity were evaluated. Anti-tumor efficacies of the three kinds of nanocarriers were evaluated on U87 malignant glioma cells (U87 MG cells) and mice-bearing malignant glioma model.T-NLCs displayed the best anti-tumor activity than other formulations in vivo and in vitro. The most significantly glioma inhibition was observed on NLCs formulations than PNPs and SLNs.This work demonstrates that NLCs can deliver TMZ into U87MG cells more efficiently, with higher inhibition efficacy than PNPs and SLNs. T-NLCs could be an excellent drug delivery system for glioblastoma chemotherapy.

Jicai Zhang, Xiang Xiao, Jianming Zhu, Ziyun Gao, Xianliang Lai, Xingen Zhu, Guohua Mao Department of Neurosurgery, Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China Purpose: Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system in adults. Based on nanotechnology such as liposomes, polymeric nanoparticles, and lipid nanoparticles, recent research efforts have been aimed to target drugs to the brain. Methods: In this study, lactoferrin- and arginine–glycine–aspartic acid (RGD) dual-ligand-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers (L/R-T/V-NLCs) were introduced for GBM combination therapy. The physicochemical properties of L/R-T/V-NLCs such as particle size, zeta potential, and encapsulated efficiency are measured. The drug release profile, cellular uptake, cytotoxicity, tissue distribution, and antitumor activity of L/R-T/V-NLCs are further investigated in vitro and in vivo. Results: L/R-T/V-NLCs were stable with nanosize and high drug encapsulation efficiency. L/R-T/V-NLCs exhibited sustained-release behavior, high cellular uptake, high cytotoxicity and synergy effects, increased drug accumulation in the tumor tissue, and obvious tumor inhibition efficiency with low systemic toxicity. Conclusion: L/R-T/V-NLCs could be a promising drug delivery system for glioblastoma chemotherapy. Keywords: gliomatosis cerebri, combination therapy, nanostructured lipid carriers, lactoferrin, arginine–glycine–aspartic acid peptide, vincristine, temozolomide

Hsp90 regulates the stability of oncoproteins important in tumor development and progression, and represents a potential therapeutic target. However, all Hsp90 inhibitors currently in clinical trials target Hsp90 ATPase activity and exhibit low selectivity and high toxicity. In this study, we discovered a new Hsp90 inhibitor, DCZ3112, with a novel mechanism of action. DCZ3112 directly bound to the N-terminal domain of Hsp90 and inhibited Hsp90-Cdc37 interaction without inhibiting ATPase activity. DCZ3112 inhibited the proliferation predominantly in HER2-positive breast cancer cells, including those resistant to the classical Hsp90 inhibitor geldanamycin, which mainly targets ATPase. DCZ3112 produced synergistic in vitro activity in inhibiting cell proliferation, inducing G1-phase arrest and apoptosis, and reducing AKT and ERK phosphorylation. Consistent with this, DCZ3112 alone inhibited the growth of HER2-positive BT-474 xenografts, and exhibited enhanced antitumor activity when combined with the anti-HER2 antibody trastuzumab. Importantly, DCZ3112 also significantly inhibited the growth of trastuzumab-resistant BT-474 cells, and combined treatment retained synergistic antitumor activity. Thus, our findings show that disrupting Hsp90-Cdc37 interaction may represent a promising strategy against HER2-positive breast cancer, especially those with acquired resistance to trastuzumab.

// Tong Tong 1 , Zhong Yang 2 , John W. Chen 3 , Jianming Zhu 4 , Zhenwei Yao 2 1 Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Radiology, Fudan University Huashan Hospital, Shanghai, China 3 Institute for Innovation in Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 4 Department of Radiation Oncology, The University of North Carolina, Chapel Hill, NC, USA Correspondence to: Zhenwei Yao, e-mail: aocnhnr@126.com John W. Chen, e-mail: jwchen@mgh.harvard.edu Keywords: clinical paper, magnetic resonance imaging, magnetic resonance spectroscopy, glioma, differential diagnosis Received: May 18, 2015 Accepted: August 07, 2015 Published: August 20, 2015 ABSTRACT Purpose: To determine whether the changes of [Cho/NAA] ratio in patients with glioma, measured by dynamic 1 H-MRS can be used to differentiate between high-grade and low-grade gliomas. Materials and Methods: This prospective study was approved by the institutional ethics committee. Written informed consent was obtained. Forty-nine patients with biopsy-proven glioma and 20 normal control subjects were recruited in this study. The maximum [Cho/NAA] ratios, acquired at 0 min, and at 6 min, were calculated and assessed from volume of interests (VOI) in the tumor areas and in the surrounding normal tissue for each patient. Absolute difference in the [Cho/NAA] ratios, from MRS acquired at 0 and 6 min, in high-grade glioma, low-grade glioma, and control subjects were compared. Results: The maximum [Cho/NAA] ratio acquired from the tumor area at the 0 min is 6.08 ± 2.02, which was significantly different ( p = .017) from that acquired after 6 min, 4.87 ± 2.13. The [Cho/NAA] ratio from the surrounding normal tissue area did not change significantly from spectra acquired at different times (0 min, 6 min). Absolute difference in [Cho/NAA] ratios acquired at 0 and 6 min time points were significantly higher ( P < 0.001) in high-grade glioma (= 3.86 ± 3.31) than in low-grade glioma (= 0.81 ± 0.90), and control subjects (0.061 ± 0.026, P = 0.000), while there was no significantly difference in low-grade glioma and control subjects. Conclusions: Dynamic 1 H-MRS can be useful for differential diagnosis between high-grade and low-grade gliomas as well as insight into the heterogeneity within the tumor.

Co-delivery of gene and anticancer drug into the same cancer cells or tissues by multifunctional nanocarriers may provide a new paradigm in cancer treatment. In this study, nanostructured lipid carriers (NLCs) were constructed as multifunctional nanomedicine for co-delivery of enhanced green fluorescence protein plasmid (DNA) and temozolomide (TMZ).TMZ- and DNA-loaded NLCs (TMZ/DNA-NLCs) were prepared. Their particle size, zeta potential, gene-loading capacity (GL) and drug encapsulation efficiency (EE) were evaluated. In vitro cytotoxicity study TMZ/DNA-NLCs was tested in U87 malignant glioma cells (U87 MG cells). In vivo gene transfection and anti-tumor efficacy of the carriers were evaluated on mice bearing malignant glioma model.The optimum TMZ/DNA-NLCs formulations with the particle size of 179 nm and with a +23 mV surface charge; got 91% of GL and 83% of EE. The growth of U87 MG cells in vitro was obviously inhibited. TMZ/DNA-NLCs also displayed the highest gene transfection efficiency and the best antitumor activity than other formulations in vivo.The results demonstrated that TMZ/DNA-NLCs were efficient in selective delivery to malignant glioma cells. Also TMZ/DNA-NLCs transfer both drug and gene to the gliomatosis cerebri, enhance the antitumor capacity and gene transfection efficacy. Thus, TMZ/DNA-NLCs could prove to be a superior co-delivery nanomedicine to achieve therapeutic efficacy and this report could be a new promising strategy for treatment in malignant gliomatosis cerebri.

The optimization of a series of fused β-homophenylalanine inhibitors of dipeptidyl peptidase-4 (DPP-4) is described. Modification on the P2-binding moiety of 6 (IC50 = 10 nM) led to the discovery of β-homophenylalanine derivatives containing pyrrolidin-2-ylmethyl amides. The introduction of a sulfamine in the meta position of the phenyl ring improved the potency against DPP-4 (6-12-fold increase). Compound 14k showed DPP-4 inhibitory activity with an IC50 value of 0.87 nM. Meanwhile, in vivo experiments exhibited that 14h had an efficiency comparable to sitagliptin at the dose of 10 mg/kg.

Glioma is a well‑known aggressive and malignant brain tumor, and accounts for ~30% of all brain and central nervous system tumors. A number of studies have indicated that the abnormal expression of specific microRNAs (miR) serves vital roles in the tumorigenesis and tumor development of human cancer, including glioma. miR‑216b has been studied in a number of types of cancer. However, the expression pattern, molecular function and underlying mechanisms of miR‑216b in glioma remain unclear. In the present study, it was demonstrated that the level of miR‑216b was significantly decreased in glioma tissues and cell lines compared with matched normal tissues and primary normal human astrocytes. The reduced miR‑216b expression level was correlated with the Karnofsky Performance Score and the World Health Organization grade of gliomas. Upregulation of miR‑216b repressed cell proliferation and invasion in glioma. Additionally, metadherin (MTDH) was identified as a direct target gene of miR‑216b in glioma. MTDH expression was demonstrated to be significantly upregulated and inversely associated with miR‑216b expression in glioma specimens. MTDH knockdowns could simulate the cellular conditions induced by miR‑216b overexpression in glioma cells. In addition, miR‑216b regulated phosphatidylinositol 3,4,5‑trisphosphate 3‑phosphatase and dual‑specificity protein phosphatase PTEN/protein kinase B signaling pathways in glioma. These results suggested that miR‑216b acted as a tumor suppressor in glioma by directly targeting MTDH and that the miR‑216b/MTDH axis may be an effective therapeutic target for the treatment of patients with this disease.

Objective The aim of this study was to investigate the clinical efficacy of superficial temporal artery-middle cerebral artery anastomosis (STA-MCA) + encephalo-duro-myo-synangiosis (EDMS) in treating ischemic Moyamoya disease (IMD) in adults. Methods A total of 30 adult patients with IMD were selected to be included in the study; they underwent STA-MCA + EDMS and were followed up for 3 months to 2 years. The digital subtraction angiography findings, modified Rankin scale (mRs) score, and complications of all the patients were compared. Results Thirty patients successfully completed the surgery. Three patients had postoperative complications (two patients with cerebral infarction on the surgical side and one patient with poor scalp healing). The postoperative morbidity rate was 10%. Angiography conducted at 3 to 6 months postoperatively showed 28 cases of anastomotic patency; the anastomotic patency rate was 93.3%. The mRs scores of the patients’ neurological function 3 months after surgery were lower than those before surgery. Conclusion STA-MCA + EDMS is effective in treating Moyamoya disease.

An efficient new way to access two regio-isomeric dibenzoxazepinones is reported from 8-aminoquinoline benzamides and 2-bromophenols. Through choice of conditions, the reaction proceeds either through a sequential C-H etherification and subsequent Goldberg reaction, both controlled by the aminoquinoline group and Cu(I), or via a C-H etherification and subsequent Smiles rearrangement promoted by Cu(II) and t-BuOK. The 8-aminoquinoline moiety, e.g., 8-amino-5-methoxyquinoline, is readily removable from the structures of dibenzoxazepinones under moderate conditions.

An efficient new way to access two regio-isomeric dibenzoxazepinones is reported from 8-aminoquinoline benzamides and 2-bromophenols. Through choice of conditions, the reaction proceeds either through a sequential C-H etherification and subsequent Goldberg reaction, both controlled by the aminoquinoline group and Cu(I), or via a C-H etherification and subsequent Smiles rearrangement promoted by Cu(II) and t-BuOK. The 8-aminoquinoline moiety, e.g., 8-amino-5-methoxyquinoline, is readily removable from the structures of dibenzoxazepinones under moderate conditions.

For thousands of years, cinnamon has been used as a traditional treatment in China. However, there are no studies to date that investigate whether cinnamon supplements are able to aid in the treatment of type 2 diabetes in Chinese subjects. We hypothesized cinnamon should be effective in improving blood glucose control in Chinese patients with type 2 diabetes. To address this hypothesis, we performed a randomized, double-blinded clinical study to analyze the effect of cinnamon extract on glycosylated hemoglobin A(1c) and fasting blood glucose levels in Chinese patients with type 2 diabetes. A total of 66 patients with type 2 diabetes were recruited and randomly divided into 3 groups: placebo and low-dose and high-dose supplementation with cinnamon extract at 120 and 360 mg/d, respectively. Patients in all 3 groups took gliclazide during the entire 3 months of the study. Both hemoglobin A(1c) and fasting blood glucose levels were significantly reduced in patients in the low- and high-dose groups, whereas they were not changed in the placebo group. The blood triglyceride levels were also significantly reduced in the low-dose group. The blood levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and liver transaminase remained unchanged in the 3 groups. In conclusion, our study indicates that cinnamon supplementation is able to significantly improve blood glucose control in Chinese patients with type 2 diabetes.

Heat shock protein 90 (HSP90) is essential for cancer cells to assist the function of various oncoproteins, and it has been recognized as a promising target in cancer therapy. Although the HSP90 inhibitors in clinical trials have shown encouraging clinical efficacy, these agents induce heat shock response (HSR), which undermines their therapeutic effects. In this report, we detailed the pharmacologic properties of 4-(2-((1H-indol-3-yl)methylene)hydrazinyl)-N-(4-bromophenyl)-6-(3,5- dimethyl-1H -pyrazol-1-yl)-1,3,5-triazin-2-amine (X66), a novel and potent HSP90 inhibitor. X66 binds to the N-terminal domain in a different manner from the classic HSP90 inhibitors. Cellular study showed that X66 depleted HSP90 client proteins, resulted in cell cycle arrest and apoptosis, and inhibition of proliferation in cancer cell lines. X66 did not activate heat shock factor-1 (HSF-1) or stimulate transcription of HSPs. Moreover, the combination of X66 with HSP90 and proteasome inhibitors yielded synergistic cytotoxicity which was involved in X66-mediated abrogation of HSR through inhibition of HSF-1 activity. The intraperitoneal administration of X66 alone depleted client protein and inhibited tumor growth, and led to enhanced activity when combined with celastrol as compared to either agent alone in BT-474 xenograft model. Collectively, the HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development.

Given the limitations and risks associated with current treatments for common bile duct (CBD) stones, the authors placed a spontaneously removed endobiliary J stent in the distal CBD to decompress the biliary tract and performed a primary closure of the CBD after laparoscopic common bile duct exploration (LCBDE).In this study, 10 of 14 patients with a diagnosis of choledocholithiasis were successfully treated using LCBDE. After extraction of the CBD stones using a choledoscope, a J-shaped stent was placed into the distal CBD as an internal drainage. The J stent was fixed with a rapid absorbable suture at the choledochotomy, which was closed by primary suture.The procedures for all 10 patients were successfully completed. No complications related to placement of the endobiliary J stents were observed postoperatively. None of the patients reported discomfort, and the J stents passed spontaneously 2 to 3 weeks after discharge.Spontaneously removed endobiliary J-stent drainage is a safe and effective surgical technique that allows for straightforward postoperative management after LCBDE.

Gynecomastia is an abnormal enlargement of one or both breasts in men. Breast-reduction surgery can help those patients who feel anxious about their abnormal appearance. Surgical treatment of gynecomastia is to excise the excess glandular tissue, which can be performed alone or in conjunction with liposuction. With two successful cases, we proposed that the endoscopic removal of gynecomastia tissue is an innovative, effective surgical treatment.Through three small incisions along the mid-axillary line, we surgically treated 2 young gynecomastia patients under an endoscope. The man first was 25 years old, with a developed right breast for 3 years, which was grade II, according to Simon's classification. The second patient was 24 and was diagnosed as bilateral gynecomastia of grade I for 10 years.The endoscopic removal of the glandular tissue was successfully completed. Only minor postoperative complications occurred. Both patients were satisfied with the cosmetic results of the surgery.Surgical treatment of gynecomastia under an endoscope is a new modality, which presents a satisfactory cosmetic result while leaving minimal and hidden scarring and seldom causes postoperative complications.

Diabetes mellitus is a chronic disease affecting patients' daily life and increasing patients' risk of other complication. Dipeptidyl peptidase-4 (DPP-4) is a serine aminopeptidase, which is one of the validated targets for Type 2 diabetes therapy due to its regulatory effect of incretin hormone. Seven DPP-4 inhibitors are commercially available nowadays on the market as Type 2 diabetes drugs. They are all chemically synthesized compounds with good therapeutic effects, but long-term safety remains unknown. On the other hand, nature provides a rich source for search of desired safe and effective medications; and actually more than half of the drugs on market are natural product related. Therefore, a systematic search for new DPP-4 inhibitors from nature sources seems to be of great utility for developing novel antidiabetic drugs. This review summarized recent progress of DPP-4 inhibitors from natural products, revealed that both pure natural products and the crude extracts of herbs or the hydrolyzates of proteins are active as DPP-4 inhibitors. Therefore, both could be served as useful clues for developing next generation of antidiabetes medicines via inhibiting DPP-4 activity.

Combined with atomic force microscope (AFM), micro-Raman spectroscope, cross-section transmission electron microscope (TEM) and high resolution electron microscope (HREM) analyses, the surface morphology and structures of a-Si:H/a-SiN x :H multilayers (MLs), irradiated by excimer laser through the phase shifting mask grating, are investigated. It is found that Si nanocrystallites (nc-Si) are formed within the initial a-Si:H sublayers, and the size of the grains can be controlled due to the constrained crystallization effect. And it is possible to use this laser interference crystallization (LIC) method to get the periodic distribution of nc-Si in both transverse and longitudinal direction.

A series of representative street dust samples were collected from a heavily industrialized city, Zhuzhou, in central China, with the aim to investigate the spatial distribution and pollution status of 17 trace metal/metalloid elements. Concentrations of twelve elements (Pb, Zn, Cu, Cd, Hg, As, Sb, In, Bi, Tl, Ag and Ga) were distinctly amplified by atmospheric deposition resulting from a large scale Pb/Zn smelter located in the northwest fringe of the city, and followed a declining trend towards the city center. Three metals (W, Mo and Co) were enriched in samples very close to a hard alloy manufacturing plant, while Ni and Cr appeared to derive predominantly from natural sources. Other industries and traffic had neglectable effects on the accumulation of observed elements. Cd, In, Zn, Ag and Pb were the five metal/metalloids with highest pollution levels and the northwestern part of city is especially affected by heavy metal pollution.

In this study for searching novel B-Raf(V600E) inhibitors, pharmacophore-based virtual screening identified 1 as a hit bearing 5-benzylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-dione. Based on 1, scaffold hopping inspired by molecular docking discovered 5-(furan-2-ylmethylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione as a new and better scaffold. Substructure search with the new scaffold identified 28 active compounds, among which 12 compounds (42.9%) showed IC(50) less than 1 μM. Especially, compound 3o, which is 10-fold more potent than the hit 1, is a potent inhibitor comparable to that of the marketed drug vemurafenib.