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Tyrosine kinases expressed by BCR-ABL fusion genes can cause changes in cell proliferation, adhesion, and survival properties, which are the main causes of chronic myelogenous leukemia (CML). Inhibiting the activity of BCR-ABL tyrosine kinase has become one of the effective methods for the treatment of chronic myelogenous leukemia. Initially, imatinib was the first small molecule of BCR-ABL tyrosine kinases inhibitors (TKIs) for the effective treatment of chronic myelogenous leukemia. Later, due to the emergence of various BCR-ABL mutations, especially T315I mutation, imatinib developed strong resistance. The second-generation kinase inhibitors dasatinib and nilotinib were able to overcome most of the mutation resistance but not T315I mutations. Therefore, in order to further overcome the problem of drug resistance, new types of KTIs such as flumatinib and radotinib have been developed, providing more options for clinical treatment. Some new drugs have entered clinical trials. In this review, two new BCRABL inhibitors (flumatinib and radotinib) and five new BCR-ABL inhibitors have been introduced into the clinical market in recent years. We reviewed their research status, synthesis methods, and clinical applications.

Metastatic breast cancer is a leading health burden worldwide. Previous studies have shown that metadherin (MTDH) promotes breast cancer initiation, metastasis and therapy resistance; however, the therapeutic potential of targeting MTDH remains largely unexplored. Here, we used genetically modified mice and demonstrate that genetic ablation of Mtdh inhibits breast cancer development through disrupting the interaction with staphylococcal nuclease domain-containing 1 (SND1), which is required to sustain breast cancer progression in established tumors. We performed a small-molecule compound screening to identify a class of specific inhibitors that disrupts the protein–protein interaction (PPI) between MTDH and SND1 and show that our lead candidate compounds C26-A2 and C26-A6 suppressed tumor growth and metastasis and enhanced chemotherapy sensitivity in preclinical models of triple-negative breast cancer (TNBC). Our results demonstrate a significant therapeutic potential in targeting the MTDH–SND1 complex and identify a new class of therapeutic agents for metastatic breast cancer. Kang and colleagues identify a specific compound blocking MTDH1–SND1 interaction, which prevents metastatic breast cancer progression, induces regression of established metastasis in preclinical models and restores chemosensitivity.

Shui Fu,1 Xian-Guo Wu,2 Liang Zhang,1 Li-Feng Wu,1 Zhang-Mei Luo,1 Qi-Lei Hu1 1Department of Clinical Laboratory, The First People’s Hospital of Yuhang District, Hangzhou, Hangzhou, Zhejiang, 311100, People’s Republic of China; 2Department of Clinical Laboratory, The Second Affiliated Hospital Zhejiang University School Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Qi-Lei HuDepartment of Clinical Laboratory, The First People’s Hospital of Yuhang District, Hangzhou, No. 369 Yingbin Road of Nanyuan Street, Linping District, Hangzhou, 311100, People’s Republic of ChinaTel +86 571 89369404Email egglandmine@163.comObjective: To explore the application effect of lean management in improving the quality of outpatient blood collection services.Methods: For this study, a total of 146,907 patients whose blood was sampled by outpatient services between April 2020 and September 2020 were selected. We analyzed the influence of various factors on the waiting time and satisfaction levels of the patients for blood collection and eliminated confounders based on the results of the analysis. Lean management for the outpatient blood collection service was implemented in July 2020. Thus, the 38,275 cases sampled on weekday mornings between April and June 2020 were selected as the ordinary management group, while the 39,473 cases sampled on weekday mornings between July and September 2020 belonged to the lean management group. Finally, the changes in waiting time and the satisfaction levels of the patients were evaluated.Results: The age and gender of the patients and the length of service of the staff, who administered blood collection had a negligible effect on the waiting time (Z=− 1.243, P=0.418; Z=− 1.569, P=0.389; Z = − 1.062, P= 0.563), while there was a statistical difference in the waiting time between different days and different sessions (Z = − 2.581, P = 0.013 and Z = − 4.672, P < 0.001). We also found that the length of service of blood collection staff, day, session, and age and gender of patients did not have a meaningful effect on patient satisfaction (P > 0.05). Overall, the median waiting time of outpatients decreased from 22 min to 13 min after the implementation of lean management (Z =10.522, P < 0.001), while the satisfaction level of outpatients increased from 95.37% to 98.33% (χ2 = 559.580, P < 0.001).Conclusion: The application of lean management can significantly shorten outpatient waiting time for blood collection, improve patients satisfaction levels, and enhance the overall patient experience. Thus, lean management can significantly improve the service quality of outpatient blood collection.Keywords: lean management, outpatient blood collection, waiting time, satisfaction, service quality

Acute lung injury (ALI) is a life-threatening clinical syndrome with high morbidity and mortality. The main pathological features of ALI are increased alveolar-capillary membrane permeability, edema, uncontrolled migration of neutrophils to the lungs, and diffuse alveolar damage, resulting in acute hypoxemic respiratory failure. Glucocorticoids, aspirin, and other anti-inflammatory drugs are commonly used to treat ALI. Respiratory supports, such as a ventilator, are used to alleviate hypoxemia. Many treatment methods are available, but they cannot significantly ameliorate the quality of life of patients with ALI and reduce mortality rates. Herbal active ingredients, such as flavonoids, terpenoids, saponins, alkaloids, and quinonoids, exhibit advantages for ALI prevention and treatment, but the underlying mechanism needs further study. This paper summarizes the role of herbal active ingredients in anti-ALI therapy and progresses in the understanding of their mechanisms. The work also provides some references and insights for the discovery and development of novel drugs for ALI prevention and treatment.

In this paper, the problems of finite-time stability analysis and finite-time stabilization are investigated for Markovian jump linear systems with incomplete transition descriptions. Two sufficient conditions are proposed to guarantee that the system states do not exceed a certain threshold in mean-square sense during a specified time interval for the continuous-time Markovian jump linear systems with partly unknown transition rates and the discrete-time Markovian jump linear systems with partly unknown transition probabilities, respectively. On the basis of the above results, two state feedback controllers are developed to solve the finite-time stochastic stabilization problems of the considered systems in continuous-time domain and discrete-time domain, respectively. For the sake of computational convenience, all the conditions are cast in the format of linear matrix inequalities (LMIs). The main feature of the proposed methods is that the total number of LMIs is much less than that in some existing results. Thus, the solution of the finite-time controllers is more concise both in theory and in engineering. In the end, the validity of the developed theoretical results are demonstrated by two illustrative examples.

Tumor growth inhibition can be achieved by inhibiting angiogenesis, which has been a field of great concern in recent years. Important targets to inhibit angiogenesis include vascular endothelial growth factor receptor (VEGFR) and its homologous tyrosine kinase receptor. Anti-angiogenic therapy based on inhibition of VEGFR-2 is an effective clinical treatment strategy. The research progress of VEGFR-2 inhibitors is reviewed in this paper from the aspects of drug development and chemical synthesis.

Urinary tract infections (UTIs) are among the most frequent causes for antibiotic prescription and; therefore, alternative treatment options for UTIs can potentially reduce antibiotic usage and development of resistance. To evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDS) for the treatment of uncomplicated lower UTIs in women, this study implemented a meta-analytic approach to evaluate the results of available randomized clinical studies from online databases. A total of four trials involving 1144 patients with uncomplicated lower UTIs were included in the final evaluation. Results showed that symptom resolution at Day 3–4 in the NSAIDs group was significantly lower than that in the antibiotics group [pooled odds ratio (OR) = 0.41, 95% confidence interval (CI): 0.23–0.74, P < 0.05]. However, there was no significant difference between the NSAIDs and antibiotics groups in symptom resolution at Day 7 (pooled OR = 0.43, 95% CI: 0.17–1.06, P = 0.07), secondary antibiotic treatment rate at Day 28–30 (pooled OR = 1.15, 95% CI: 0.16–7.98, P = 0.89) and adverse events rate (pooled OR = 1.09, 95% CI: 0.61–1.96, P = 0.77). Therefore, this meta-analysis suggests that, although inferior to antibiotics in fast symptom resolution, symptomatic treatment with NSAIDs can be considered as an alternative treatment option for uncomplicated lower UTIs in women. However, given the low number of randomized controlled trials that met inclusion criteria in this meta-analysis, efficacy of NSAIDs for treatment of uncomplicated lower UTIs should be further evaluated in more comprehensive clinical studies.

The relative pose (position and attitude) measurement of space noncooperative targets is very important for on-orbit servicing activities, such as target tracking, approaching, and capturing. The traditional methods rarely consider the instability of feature extraction and image blurring caused by target tumbling. In this paper, a method based on the maximum outer contour (MOC) recognition is proposed to measure the pose of the target. Different feature extraction algorithms can simultaneously achieve close- and long-range measurement tasks. First, the trailing image is restored by the image enhancement method. Second, the “rough + fine” combination recognition method is used for contour extraction and connected component labeling of the restored image, and the target feature extraction time is reduced to one-third of traditional methods. Furthermore, the elliptical surface on the MOC is fitted by the least squares method (LSM), and the ellipse parameters (i.e., the center position, the long- and short-axes, and the deflection angle) are extracted. The accuracy of the target recognition is improved. Third, for the close-range measurement, based on the detected ellipse parameter, the pose of the noncooperative target is solved by the binocular imaging algorithm of the space circle; for the long-range measurement, the contour centroid of the target is calculated by the detected MOC, and the position of the target is solved by the LSM. Moreover, the effectiveness of the method is verified by the OpenSceneGraph numerical simulation system. Finally, an experimental system consisting of a binocular camera, a UR5 manipulator, and a satellite mockup was built. The experimental results verified the proposed method.

Purpose The overall survival (OS) of patients diagnosed with stage II‐III colorectal cancer (CRC) can vary greatly, even between patients with the same tumor stage. We aimed to design a nomogram to predict OS in resected, stage II‐III CRC and stratify patients with CRC into different risk groups. Patients and Methods Based on data from 873 patients with CRC, we used univariate Cox regression analysis to select the significant prognostic features, which were subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for feature selection. Cross‐validation was used to confirm suitable tuning parameters (λ) for LASSO logistic regression. Then, the nomogram was used to estimate 3‐ and 5‐year OS based on the multivariable Cox regression model. The survival curves of the two groups were produced using the Kaplan‐Meier method. Risk group stratification was performed to assess the predictive capacity of the nomogram. Results Preoperative mean platelet volume, preoperative platelet distribution width, monocytes, and postoperative adjuvant chemotherapy were identified as independent prognostic factors by LASSO regression and integrated for the construction of the nomogram. The nomogram provided good discrimination, with C‐indices of 0.67 and 0.69 for the training and validation sets, respectively. Calibration plots illustrated excellent agreement between the nomogram predictions and actual observations for 3‐ and 5‐year OS. Moreover, a significant difference in OS was shown between patients stratified into different risk groups (P, Four points are allocated for preoperative mean platelet volume, preoperative platelet distribution width, monocytes, and postoperative adjuvant chemotherapy. Nomogram for predicting 3‐ and 5‐year probabilities of colorectal cancer patients was established. Draw a vertical straight line from the variable value to the axis labeled “Points”. Then calculate all variables’ points. The total points on the bottom scales that correspond to the 3‐ and 5‐year survival were showed apparently.

High-quality axis-encircling electron beam is essential to drive a high-harmonic gyrotron. A magnetic cusp gun that can generate a low-spread axis-encircling electron beam at an extremely high magnetic-compression ratio was developed for a 1-THz fourth-harmonic gyrotron toward continuous-wave operation. The optimized gun could generate an axis-encircling electron beam with 80-kV voltage, 1-A current, and a nearly constant pitch factor of about 1.5 in a wide range of magnetic field strength. The transverse velocity spread was less than 2.1% and the guiding center radius was 26.6 μm. The design was verified by using MAGIC, EGUN, and CST simulations and good agreements were achieved.

PurposeTo evaluate the value of F-18 FDG PET/CT in the differentiation of malignant and benign upper urinary tract-occupying lesions.Patients and Methods64 patients with upper urinary tract-occupying lesions underwent F-18 FDG PET/CT at RenJi Hospital from January 2015 to February 2019 in this retrospective study. Of the 64 patients, 50 patients received nephroureterectomy or partial ureterectomy; 14 patients received ureteroscopy and biopsy. The comparisons of PET/CT parameters and clinical characteristics between malignant and benign upper urinary tract-occupying lesions were investigated.ResultsOf the 64 patients, 49 were found to have malignant tumors. Receiver operating characteristic analysis determined the lesion SUVmax value of 6.75 as the threshold for predicting malignant tumors. There were significant associations between malignant and benign upper urinary tract-occupying lesions and SUVmax of lesion (P6.75) and negative (SUVmax ≤6.75) PET groups in 38 of the 49 patients with malignant tumors.ConclusionThe SUVmax of lesion and patient age is associated with the nature of upper urinary tract-occupying lesions. F-18 FDG PET/CT may be useful to distinguish between malignant and benign upper urinary tract-occupying lesions and determine a suitable therapeutic strategy.

Noncooperative target pose (position and attitude) measurement is very important for on-orbital servicing tasks, such as malfunctioned spacecraft capturing and repairing, space debris removal, and so on. Traditional stereovision-based methods require the two cameras to observe the same object and form a common observation area, limiting system flexibility, and measurement distance. In this paper, a virtual stereovision (VSV) modeling and pose measurement method are proposed for a dual-arm space robotic system. Each arm only carries one camera to observe different objects. The geometry features (i.e., the triangle, quadrilateral, or circular features) are independently extracted from the images of each camera. The two separate cameras are mapped to a stereo measurement range and the, respectively, identified features are converted into an equivalent “virtual common feature.” Then, a “VSV measurement system” is constructed. The rocket nozzle and the triangular support of the satellite are considered as different objects to be observed by the two cameras of a dual-arm space robot. The pose of the nozzles and the triangular brackets is further achieved based on the VSV information. Finally, we developed an experimental system, which is composed of a satellite mockup, two monocular cameras, and high precision laser tracker (used to evaluate the vision measure accuracy). The experimental results verified the proposed method. The average position error of the method is less than 6.1367 mm, and the average attitude error is less than 2.415°.

The helicopter tail drive shaft system is a typical multi-point supported drive shaft system, with a long span that can lead to serious vibration problems. Shaft vibration can be effectively reduced by installing a rubber-silicone oil combined damper between the bearing and bearing pedestal at the support point along the tail drive shaft. Stiffness and damping characteristics of the rubber-silicone oil combined damper are important factors affecting shaft vibration. In this study, the effects of silicone oil on the stiffness and damping of rubber-silicone oil combined damper were analyzed through simulations. The simulation method was experimentally verified and factors influencing the static stiffness, dynamic stiffness, and damping characteristics of the damper were investigated. In addition, the influence of damper dimensions and external excitation frequency on the stiffness and loss factor of the damping ring in the presence and absence of silicone oil were examined. The presence of silicone oil increases the difference between the dynamic stiffness and the loss factor. As the viscosity of the silicone oil increases, the static stiffness, dynamic stiffness, and loss factor of rubber-silicone oil combined dampers increase. The results have important guiding significance in the design of dampers for shafting systems.

In this paper, the attitude tracking control problem for rigid spacecraft is investigated in the presence of parameter uncertainties and external disturbances. An extended state observer is designed to estimate the parameter uncertainties and external disturbances. Then, by using the obtained estimation, a robust finite-time controller is proposed to achieve attitude tracking for the rigid spacecraft via the backstepping technique. The practical finite-time stability of the closed-loop system under the presented controller is proven by the Lyapunov stability theory. Finally, some simulation results are provided to illustrate the effectiveness and superiority of the proposed controller compared with some existing control schemes.

OBJECTIVE To observe the effect of zoledronic acid on the reduction of acute bone loss and fracture rate in elderly postoperative patients with intertrochanteric fracture. METHODS From August 2012 to January 2015, a total of 482 patients with senile osteoporotic femoral intertrochanteric fracture, who accepted proximal femoral intramedullary fixation under anesthesia were analysed. The patients were divided into two groups. Treatment group (353 cases) were treated with 100 mL/5 mg of zoledronic acid injection in 1 week after operation, as well as orally taken 600 mg/d of calcium carbonate and active vitamin D3 400 IU/d. Control group (129 cases) were given the same dose of calcium carbonate and active vitamin D3 orally. Efficacy evaluation were conducted during different periods of medication RESULTS: Compared with pre-medication, indexes of bone metabolism (TARP-5b, CTX) in the treatment group were brought down, especially significantly statistically different after 12 months of medication. The treatment group performed superior to control group in alleviating the pain of back and posture changing (P

The chemokine C-C motif ligand 11, also known as eotaxin-1, has been identified as a novel mediator of inflammatory bone resorption. However, little is known regarding a potential role for CCL11/Eotaxin-1 in postmenopausal osteoporosis.The scope of this study was to explore the relationship between serum CCL11/Eotaxin-1 concentrations and disease progression of postmenopausal females with osteoporosis.A total of 83 postmenopausal women diagnosed with osteoporosis were enrolled. Meanwhile, 82 postmenopausal women with normal bone mineral density (BMD) and 85 healthy controls inner child-bearing age were enrolled as control. The Dual-energy X-ray absorptiometry was used to examine the BMDs at the femoral neck, lumbar spine 1-4 and total hip of all participants. Serum CCL11/Eotaxin-1 levels were examined by enzyme-linked immunosorbent assay. We also included inflammation marker interleukin-6 (IL-6) as well as a serum marker of bone resorption C-telopeptide cross-linked collagen type 1 (CTX-1). The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were recorded to evaluate the clinical severity in POMP females.Serum CCL11/Eotaxin-1 levels were significantly elevated in postmenopausal osteoporotic patients PMOP patients compared with PMNOP and healthy controls. We observed a significant negative correlation of serum CCL11/Eotaxin-1 levels with lumbar spine, femoral neck and total hip BMD. Furthermore, serum CCL11/ Eotaxin-1 concentrations were also positively related to the VAS and ODI scores. Last, serum CCL11/ Eotaxin-1 concentrations were positively associated with IL-6 and CTX-1 levels. These correlations remain significant after adjusting for age and BMI. Multivariate linear regression analysis demonstrated that CCL11/Eotaxin-1 could serve as an independent marker.Serum CCL 11/Eotaxin-1 may serve as a candidate biomarker for postmenopausal osteoporosis. Therapeutics targeting CCL11/Eotaxin-1 and its related signalling way to prevent and slow progression of PMOP deserve further study.Hemokin (C-C motiv) ligand 11, poznat i pod nazivom eotaksin-1, identifikovan je kao novi posrednik zapaljenske resorpcije kostiju. Međutim, malo se zna o potencijalnoj ulozi CCL11/Eotaksin-1 u postmenopauzalnoj osteoporozi.Cilj Cilj ove studije bio je istraživanje odnosa između serumskih koncentracija CCL11/Eotaksin-1 i progresije bolesti osteoporoze kod žena u postmenopauzi.U istraživanju su ukupno učestvovale 83 žene sa dijagnozom osteoporoze u postmenopauzi. U međuvremenu su u studiju uključene 82 žene u postmenopauzi sa normalnom mineralnom gustinom kostiju (BMD) i 85 zdravih žena sposobnih za rađanje kao kontrolna grupa. Za ispitivanje BMD-a na vratu femura, lumbalne kičme 1–4 i celog kuka svih učesnica korišćena je dvoenergentska rentgenska apsorpciometrija. Serumske koncentracije CCL11/Eotakisn-1 su ispitane pomoću enzimski vezanih imunosorbentnih testova. Takođe smo uključili i inflamatorni marker interleukin-6 (IL-6), kao i serumski marker koštane resorpcije C-telopeptidnog ukrštenog kolagena tipa 1 (CTKS-1). Zabeleženi su rezultati na Vizuelnoanalognoj skali (VAS) kao i Oswestry indeks invalidnosti (ODI) za procenu ozbiljnosti kliničke slike kod žena sa postmenopauzalnom osteoporozom.Serumski CCL11/Eotaksin-1 nivoi su bili značajno povišeni kod pacijenata sa postmenopauzalnom osteoporozom (PMOP) u poređenju sa PMNOP i zdravom kontrolnom grupom. Posmatrali smo značajnu negativnu korelaciju serumskih nivoa CCL11/Eotaksin-1 sa BMD-omlumbalne kičme, vratom femura i celog kuka. Pored toga, serumska koncentracija CCL11/Eotaksin-1 takođe je pozitivno povezana sa rezultatima VAS i ODI. Poslednje, serumska koncentracija CCL11/ Eotaksin-1 je bila pozitivno povezana sa nivoima IL-6 i CTKS-1. Ove korelacije i dalje ostaju značajne nakon usklađivanja sa godinama i BMI. Multivarijantna linearna regresiona analiza pokazala je da CCL11/Eotaksin-1 može poslužiti kao nezavisni marker.Serumski CCL 11/Eotaksin-1 može poslužiti kao kandidat za biomarker za postmenopauzalna osteoporozu. Terapija koja targetira CCL11/Eotaksin-1 i njegov signalni put u cilju sprečavanja i usporavanja progresije PMOP-a zaslužuje dalja istraživanja.

The pose (position and attitude) measurement of space non-cooperative targets is one of the key technologies in on-orbit service. Traditional stereo-vision-based methods are easily affected by illumination conditions, while the 3D laser radar has a good stability, but the point cloud is sparse. In this paper, a method based on the 3D laser radar and stereo-vision information is proposed to measure the pose and estimate the motion for non-cooperative targets. The proposed method can not only adapt to the harsh lighting conditions, but also has better robustness and higher precision. First, find the matching point corresponding to the binocular camera by using the stereo matching algorithm, and then, calculate the 3D coordinates of the matching points according to the least squares method. Combined with the fusion calibration result, the point cloud data acquired by the 3D laser radar is converted to the left camera frame. Second, integrate the point cloud data obtained by the above two sensors to obtain a complete point cloud model of the non-cooperative target. Third, the obtained point cloud model is registered, and the rigid transformation matrix of two adjacent point clouds is solved. Then, the relative pose and velocity (linear velocity and angular velocity) of the non-cooperative target are estimated by the extended Kalman filter (EKF) algorithm. Finally, an experimental system was built. It consists of a UR5 robot, a satellite mockup, two cameras, a 3D laser radar, and an API laser tracker (for evaluating the accuracy of measurement), was built. The experiment results verified the proposed method.

In this paper, a terminal sliding mode controller based on disturbance observer is designed for rigid spacecraft. A disturbance observer is first proposed for the unmeasurable disturbance. The disturbance estimation error converges to zero in finite time. By combining this proposed observer with the sliding mode control technique, then a finite time attitude control law is presented for the rigid spacecraft. The variable boundary layer saturation function is used in the design of the switching portion of the terminal sliding mode controller to reduce chattering. The convergence of the observer and closed-loop system is proved by the Lyapunov stability theory.

Background:Hepatocellular carcinoma (HCC) is a lethal malignancy lacking effective treatment. The Cyclin-dependent kinases 4/6 (CDK4/6) and PI3K/AKT signal pathways play pivotal roles in carcinogenesis and are promising therapeutic targets for HCC. Here we identified a new CDK4/6 and PI3K/AKT multi-kinase inhibitor for the treatment of HCC.Methods:Using a repurposing and ensemble docking methodology, we screened a library of worldwide approved drugs to identify candidate CDK4/6 inhibitors. By MTT, apoptosis, and flow cytometry analysis, we investigated the effects of candidate drug in reducing cell-viability,inducing apoptosis, and causing cell-cycle arrest. The drug combination and thermal proteomic profiling (TPP) method were used to investigate whether the candidate drug produced antagonistic effect. Thein vivoanti-cancer effect was performed in BALB/C nude mice subcutaneously xenografted with Huh7 cells.Results:We demonstrated for the first time that the anti-plasmodium drug aminoquinol is a new CDK4/6 and PI3K/AKT inhibitor. Aminoquinol significantly decreased cell viability, induced apoptosis, increased the percentage of cells in G1 phase. Drug combination screening indicated that aminoquinol could produce antagonistic effect with the PI3K inhibitor LY294002. TPP analysis confirmed that aminoquinol significantly stabilized CDK4, CDK6, PI3K and AKT proteins. Finally,in vivostudy in Huh7 cells xenografted nude mice demonstrated that aminoquinol exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil with the combination treatment showed the highest therapeutic effect.Conclusion:The present study indicates for the first time the discovery of a new CDK4/6 and PI3K/AKT multi-kinase inhibitor aminoquinol. It could be used alone or as a combination therapeutic strategy for the treatment of HCC.

PurposeThis study aimed to elucidate the prognostic significance of a novel inflammation-joined and nutrition-related clinicopathological marker for colorectal cancer (CRC).MethodsVarious factors from preoperative fasting blood samples from 2471 patients with CRC were retrospectively analyzed. Factors related to prognosis were evaluated using univariate and multivariate analyses. The Kaplan–Meier method was used to generate survival curves, while the log-rank test was used to measure survival differences between groups.ResultsUnivariate analysis revealed that C-reactive protein (CRP)/mean corpuscular volume (MCV) ratio, TNM stage, differentiation, right-sided tumor, age, carcinoembryonic antigen (CEA) level, and CRP level were significantly associated with poor prognosis in CRC. In contrast, adjuvant chemotherapy is regarded as a protective factor. Elevation of CRP/MCV ratio (odds ratio [OR]: 1.535, 95% confidence interval [CI]: 1.121–2.104, P = 0.008), TNM stage (OR: 2.747, 95% CI: 2.175–3.469, P < 0.001), and differentiation (OR, 1.384; 95% CI, 1.150–1.666; P = 0.001) were prognostic risk factors in the multivariate analyses. Subgroup analysis showed that CRP/MCV, TNM staging system, and differentiation also independently affected survival in patients with lymph node-positive CRC. The nomogram based on these three indicators showed that CRP/MCV had a greater prognostic value and clinical significance for lymph node-positive patients with poorly differentiated tumors at the late stage.ConclusionA novel nomogram using the clinicopathologic index of inflammation and nutrition was constructed to predict the prognosis of CRC. Early interventions should be emphasized for advanced-stage patients with severe inflammation and poor nutritional status.

Ethnopharmacological relevance In the past five years, ethnopharmacy-based drugs have been increasingly used in clinical practice. It has been reported that hundreds of ethnopharmacy-based drugs can modulate autophagy to regulate physiological and pathological processes, and ethnomedicines also have certain therapeutic effects on illnesses, revealing the important roles of these medicines in regulating autophagy and treating diseases. Aim of the study This study reviews the regulatory effects of natural products on autophagy in recent years, and discusses their pharmacological effects and clinical applications in the process of diseases. It provides a preliminary literature basis and reference for the research of plant drugs in the regulation of autophagy. Materials and methods A comprehensive systematic review in the fields of relationship between autophagy and ethnomedicine in treating diseases from PubMed electronic database was performed. Information was obtained from documentary sources. Results We recorded some illnesses associated with autophagy, then classified them into different categories reasonably. Based on the uses of these substances in different researches of diseases, a total of 80 active ingredients or compound preparations of natural drugs were searched. The autophagy mechanisms of these substances in the treatments of divers diseases have been summarized for the first time, we also looked forward to the clinical application of some of them. Conclusions Autophagy plays a key function in lots of illnesses, the regulation of autophagy has become one of the important means to prevent and treat these diseases. About 80 compounds and preparations involved in this review have been proved to have therapeutic effects on related diseases through the mechanism of autophagy. Experiments in vivo and in vitro showed that these compounds and preparations could treat these diseases by regulating autophagy. The typical natural products curcumin and tripterine have powerful roles in regulating autophagy and show good and diversified curative effects.

Neuroinflammation, an inflammatory response within the central nervous system (CNS), is a main hallmark of common neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), among others. The over-activated microglia release pro-inflammatory cytokines, which induces neuronal death and accelerates neurodegeneration. Therefore, inhibition of microglia over-activation and microglia-mediated neuroinflammation has been a promising strategy for the treatment of neurodegenerative diseases. Many drugs have shown promising therapeutic effects on microglia and inflammation. However, the blood–brain barrier (BBB)—a natural barrier preventing brain tissue from contact with harmful plasma components—seriously hinders drug delivery to the microglial cells in CNS. As an emerging useful therapeutic tool in CNS-related diseases, nanoparticles (NPs) have been widely applied in biomedical fields for use in diagnosis, biosensing and drug delivery. Recently, many NPs have been reported to be useful vehicles for anti-inflammatory drugs across the BBB to inhibit the over-activation of microglia and neuroinflammation. Therefore, NPs with good biodegradability and biocompatibility have the potential to be developed as an effective and minimally invasive carrier to help other drugs cross the BBB or as a therapeutic agent for the treatment of neuroinflammation-mediated neurodegenerative diseases. In this review, we summarized various nanoparticles applied in CNS, and their mechanisms and effects in the modulation of inflammation responses in neurodegenerative diseases, providing insights and suggestions for the use of NPs in the treatment of neuroinflammation-related neurodegenerative diseases.

Purpose: Vascular invasion (VI) is associated with recurrence and is an indicator of poor prognosis in gastric cancer (GC). Pre-operative identification of VI may guide the selection of the optimal surgical approach and assess the requirement for neoadjuvant therapy. Methods: A total of 271 patients were retrospectively collected and randomly allocated into the training and validation datasets. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features, and multivariable logistic regression analysis was used to develop the nomogram. Results: The nomogram consisted of pre-operative serum complement C3 levels, duration of symptoms, pre-operative computed tomography stage, abdominal distension and undifferentiated carcinoma. The nomogram provided good calibration for both the training and the validation set, with area under the curve values of 0.792 and 0.774. Decision curve analysis revealed that the nomogram was clinically useful. Conclusion: The present study constructed a nomogram for the pre-operative prediction of VI in patients with GC. The nomogram may aid the identification of high-risk patients and aid the optimization of pre-operative decision-making.

Vascular calcification (VC) in macrovascular and peripheral blood vessels is one of the main factors leading to diabetes mellitus (DM) and death. Apart from the induction of vascular calcification, advanced glycation end products (AGEs) have also been reported to modulate autophagy and apoptosis in DM. Autophagy plays a role in maintaining the stabilization of the external and internal microenvironment. This process is vital for regulating arteriosclerosis. However, the internal mechanisms of this pathogenic process are still unclear. Besides, the relationship among autophagy, apoptosis, and calcification in HASMCs upon AGEs exposure has not been reported in detail. In this study, we established a calcification model of SMC through the intervention of AGEs. It was found that the calcification was upregulated in AGEs treated HASMCs when autophagy and apoptosis were activated. In the country, AGEs-activated calcification and apoptosis were suppressed in Atg7 knockout cells or pretreated with wortmannin (WM), an autophagy inhibitor. These results provide new insights to conduct further investigations on the potential clinical applications for autophagy inhibitors in the treatment of diabetes-related vascular calcification.

PurposeStudies have indicated that PSMA-positive ganglia represent a diagnostic pitfall for nuclear medicine physicians. No studies have described choline and FDG uptake in ganglia, which may be a source of misdiagnosis. Herein, we described the percentage and uptake pattern of 68Ga-PSMA, 11C-choline and 18F-FDG PET/CT in ganglia and evaluated the heterogeneous metabolic patterns of ganglia to differentiate from lymph node metastases (LNM).MethodsThirty-nine patients who underwent 11C-choline PET/CT and 120 patients who underwent 68Ga-PSMA PET/CT and 18F-FDG PET/CT were retrospectively analyzed. The prevalence of PSMA-positive, choline-positive and FDG-positive ganglia was determined, the SUVmax of ganglia in different locations were measured, and the configuration was described. The SUVmax cutoff of PSMA-PET, choline-PET and FDG-PET was determined by ROC curve analysis to differentiate ganglia from LNM.Results329 PSMA-positive ganglia were identified in 120 patients, 95 choline-positive ganglia were identified in 39 patients, and 39 FDG-positive ganglia were identified in 34 patients. PSMA-positive uptake was observed in 98.3%, 95.8%, and 80.0% of cervical, coeliac, and sacral ganglia, respectively. Choline-positive uptake was observed in 84.6%, 97.4%, and 61.5% of cervical, coeliac, and sacral ganglia, respectively. FDG-positive uptake was observed in 16.7%, 13.3%, and 2.5% of cervical, coeliac, and sacral ganglia, respectively. Cervical and coeliac ganglia had a higher rate of PSMA-positive uptake than sacral ganglia. Choline uptake was highest in coeliac ganglia followed by cervical and sacral ganglia. PSMA, choline or FDG uptake in LNM was all significantly higher than ganglia. ROC curve analysis revealed that at a 4.1 SUVmax cutoff of PSMA-PET, the sensitivity, specificity and accuracy of LNM identification was 88.4%, 97.9% and 96.2%, respectively. ROC curve analysis revealed that at a 2.35 SUVmax cutoff for choline-PET, the sensitivity, specificity, and accuracy of LNM identification was 95.0%, 92.6% and 93.0%, respectively. ROC curve analysis revealed that at a 2.55 SUVmax cutoff for FDG-PET, the sensitivity, specificity, and accuracy of LNM identification was 77.3%, 87.2%, and 81.9%, respectively. PSMA-, Choline- and FDG-positive ganglia are mainly band-shaped; most LNMs exhibited nodular and teardrop-shaped configuration.Conclusion68Ga-PSMA and 11C-choline uptake in ganglia was common, and FDG-positive ganglia were observed at lower frequency. Using 68Ga-PSMA, 11C-choline and 18F-FDG uptake and anatomic location and configuration, the differentiation of ganglia from adjacent LNM is feasible.

BACKGROUND Hepatocellular carcinoma (HCC) is a malignant tumor that occurs in the liver. Its onset is latent, and it shows high heterogeneity and can readily experience intrahepatic metastasis or systemic metastasis, which seriously affects patients’ quality of life. Numerous studies have shown that hypoxia inducible factor1α (HIF-1α) plays a significant role in the occurrence and development of tumors, as it promotes the formation of intratumoral vessels and plays a key role in their metastasis and invasion. Some studies have reported that caspase-3, which is induced by various factors, is involved in the apoptosis of tumor cells. AIM To investigate the expression of caspase-3 and HIF-1α and their relationship to the prognosis of patients with primary HCC complicated by pathological changes of hemorrhage and necrosis. METHODS A total of 88 patients with HCC complicated by pathological changes of hemorrhage and necrosis who were treated at our hospital from January 2017 to December 2019 were selected. The expression of caspase-3 and HIF-1α in HCC and paracancerous tissues from these patients was assessed. RESULTS The positive expression rate of caspase-3 in HCC tissues was 27.27%, which was significantly lower than that in the paracancerous tissues (P < 0.05), while the positive expression rate of HIF-1α was 72.73%, which was significantly higher than that in the paracancerous tissues (P < 0.05). The positive expression rates for caspase-3 in tumor node metastasis (TNM) stage III and lymph node metastasis tissues were 2.78% and 2.50%, respectively, which were significantly lower than those in TNM stage I-II and non-lymph node metastasis tissues (P < 0.05). The positive expression rates of HIF-1α in TNM stage III, lymph node metastasis, and portal vein tumor thrombus tissues were 86.11%, 87.50%, and 88.00%, respectively, and these values were significantly higher than those in TNM stage I-II, non-lymph node metastasis, and portal vein tumor thrombus tissues (P < 0.05). The expression of caspase-3 and HIF-1α in HCC tissues were negatively correlated (rs = − 0.426, P < 0.05). The median overall survival time of HCC patients was 18.90 mo (95% CI: 17.20–19.91). The results of the Cox proportional risk regression model analysis showed that TNM stage, portal vein tumor thrombus, lymph node metastasis, caspase-3 expression, and HIF-1α expression were the factors influencing patient prognosis (P < 0.05). CONCLUSION The expression of caspase-3 decreases and HIF-1α increases in HCC tissues complicated by pathological changes of hemorrhage and necrosis, and these are related to clinicopathological features and prognosis.

Background KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated. Methods 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated. Results NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes. Conclusions KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients.

ObjectiveThe aim of the study was to investigate the impacts of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) dyslipidaemia on prognosis in coronary artery disease (CAD) patients with different glucose metabolism status.DesignAn observational cohort study.Setting/participantsA total of 3057 patients with stable CAD were consecutively enrolled and divided into three groups according to different glucose metabolism status. Atherogenic dyslipidaemia (AD) was defined as TG ≥1.7 mmol/L and HDL-C Primary outcome measuresThe primary endpoints were cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke.ResultsDuring a median follow-up of 6.1 years, 308 (10.1%) CVEs occurred. No significant difference in the occurrence of CVEs was observed between normal glucose regulation (NGR) and pre-diabetes (pre-DM) groups (HR: 1.25, 95% CI 0.89 to 1.76) while DM group presented 1.45-fold higher risk of CVEs (HR: 1.45, 95% CI 1.02 to 2.05). When the participants were categorised according to combined status of two parameters, the cardiovascular risk was significantly elevated in pre-DM or DM plus AD group compared with the NGR plus non-AD group (HR: 1.76, 95% CI 1.10 to 2.80 and HR: 1.87, 95% CI 1.17 to 2.98).ConclusionsThe present study suggested that the presence of AD might affect the prognosis in patients with DM or pre-DM and stable CAD.

Nowadays corporate Intranet Security Monitoring generally relies on SIEM products or SOC platforms. The data comes from a large number of system logs, application running logs and business data, which are generated by network device, security protection device and application systems, etc., is finally stored as normalized data after word segmentation, field parsing and data type mapping. The Intranet Security Monitoring are extremely sensitive to data quality because of the efficiency and accuracy requirements, but the continuous business changes and system upgrades in the intranet environment make both of the data structure and content variable. The existing automated log parsing algorithms are mainly aimed at system logs with a fixed structure, cannot handle variable data with multiple types and structures, besides, the parsing work only completes word segmentation and field parsing. As for data type identification and mapping, there should be several security experts to wait to write static templates, in case the data is changed. In response to the above problems, an ontology model of data knowledge for Intranet Security Monitoring is constructed, and using the computing power of cloud computing, a dynamic processing algorithm for variable data (DPAVD) based on structural information entropy is proposed, in which the correlation between data fields is used as the core factor, can reduce the interference caused by the difference in character expression and meet the requirements of high-quality data for Intranet Security Monitoring.

This technical paper provides an attitude tracking strategy by employing a nonlinear model predictive controller (NMPC). To directly use the relative navigation information, the piecewise affine (PWA) model based on the Euler dynamics is adopted. Due to the singularity of Euler angles, a singularity-free strategy is proposed to complete continuous attitude tracking. Consider the sensor uncertainty and disturbance, the Kalman filter is combined with the NMPC framework. Finally, the numerical results are presented to show the control performance.

Fluoropyrimidine-based chemotherapy is an essential component of systemic chemotherapy for colorectal cancer (CRC). The immune response is implicated in chemotherapy-induced cytotoxicity. Here, we reported an immune risk (Imm-R) model for prognostic prediction in patients receiving fluoropyrimidine-based chemotherapy. Gene expression profiles and corresponding clinical information were collected from four data sets and divided into training set (n = 183) and validation set (validation set1: n = 34; validation set2: n = 99). The composition of 22 tumor-infiltrating immune cells (TIICs) populations was characterized with the CIBERSORT deconvolution algorithm. A prognostic Imm-R model for predicting overall survival was established by performing least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis. T follicular helper cells and M0 macrophages were associated with better survival, while eosinophils were associated with worse survival. TIICs signature was constructed based on the above three immune cell types. Furthermore, a Imm-R model was created by integrating TIICs signature with immune-related genes (IRGs), which effectively in distinguishing CRC patients with poorer prognosis. The Imm-R model was associated with activation of the TGF-beta signaling and suppression of DNA damage. Results of this research provide new insights into the role of immunity for in fluoropyrimidine-based chemotherapy as well as a useful tools to predict the outcome of CRC patients receiving fluoropyrimidine-based chemotherapy.

Background Previous studies have suggested that patients with diabetes mellitus (DM) have higher prevalence of atherosclerotic cardiovascular disease (ASCVD), and plasma levels of free fatty acids (FFAs) are a useful marker for predicting ASCVD. We hypothesized that FFAs could predict both coronary and carotid lesions in an individual with type 2 DM (T2DM). The present study, hence, was to investigate the relation of plasma FFA level to the presence and severity of coronary and carotid atherosclerosis in patients with T2DM. Methods Three hundred and two consecutive individuals with T2DM who have received carotid ultrasonography and coronary angiography due to chest pain were enrolled in this study. Plasma FFAs were measured using an automatic biochemistry analyzer. Coronary and carotid severity was evaluated by Gensini score and Crouse score respectively. Subsequently, the relation of FFA levels to the presence and severity of coronary artery disease (CAD) and carotid atherosclerotic plaque (CAP) in whole individuals were also assessed. Results Increased plasma FFA levels were found in the groups either CAD or CAP compared to those without. Patients with higher level of FFAs had a higher CAD (89.9%) and elevated prevalence of CAP (69.7%). And also, patients with higher level of FFAs had a higher Gensini and Crouse scores. Multivariate regression analysis showed that FFA levels were independently associated with the presence of CAD and CAP (OR = 1.83, 95%CI: 1.27–2.65, P = 0.001; OR = 1.62, 95%CI: 1.22–2.14, P = 0.001, respectively). The area under the curve (AUC) was 0.68 and 0.65 for predicting the presence of CAD and CAP in patients with DM respectively. Conclusions The present study firstly indicated that elevated FFA levels appeared associated with both the presence and severity of CAD and CAP in patients with T2DM, suggesting that plasma FFA levels may be a useful biomarker for improving management of patients with T2DM.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy.Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed.Results: The median DOT was 9.1 months (95% CI: 8.5–9.8), and the median OS was 26.2 months (95% CI: 24.2–28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set.Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

Smart Spring is a kind of active vibration control device based on piezoelectric material, which can effectively suppress the vibration of the shaft system in an over-critical state, and the selection of control strategy has great influence on the vibration reduction effect of the Smart Spring. In this paper, the authors investigate the control of the over-critical vibration of the transmission shaft system with Smart Spring, based on the ADAMS and MATLAB joint simulation method. Firstly, the joint simulation model of three-support shafting with Smart Spring is established, and the over-critical speed simulation analysis of the three-support shafting under the fixed control force of the Smart Spring is carried out. The simulation results show that the maximum vibration reduction rate is 71.6%. The accuracy of the joint simulation model is verified by the experiment of the three-support shafting subcritical vibration control. On this basis, a function control force vibration control strategy with time-varying control force is proposed. By analyzing the axis orbit of the shafting, the optimal fixed control force at different speeds is obtained, the control force function is determined by polynomial fitting, and the shafting critical crossing simulation under the function control force is carried out. The simulation results show that the displacement response of the shafting under the function control force is less than that under the fixed control force in the whole speed range.

Attitude stabilization control via disturbance observer for flexible spacecraft is studied in this paper. First, a model based on Takagi-Sugeno fuzzy system of flexible spacecraft is established. In the case of spacecraft subjected to the external disturbance, the external disturbance and flexible accessories are treated as one disturbance. Furthermore, the lumped disturbance is no longer limited by bounded or zero-order derivatives. Then, a disturbance observer is proposed to estimate it while the gains are determined by the convergence condition of the estimation error. According to the obtained estimate, an integral sliding surface is selected so that the control law is partially composed of PDCC. At last, the effectiveness of the disturbance observer and attitude control law are illustrated by an example of a flexible spacecraft.

Aiming at the unsatisfactory effect of three-dimensional reconstruction of multi-scale image set and the fact that the reconstruction effect of large-scale scenes such as buildings is not realistic and the details are not prominent, this paper proposes a new image enhancement algorithm to preprocessed images, and uses the floating scale surface reconstruction algorithm to improve the surface reconstruction effect. Firstly, an image enhancement algorithm is proposed, which is based on histogram equalization. Secondly, the Structure from Motion algorithm is used to recover camera parameters, extract and match features, and generate sparse point clouds. And then，the MVS algorithm is used for dense reconstruction. Finally, the floating scale surface reconstruction algorithm is used for reconstruction. The experiment proved the proposed image enhancement algorithm improves the effect of feature point extraction. The surface reconstruction algorithm we use is efficiently for surface reconstruction and improves the 3D reconstruction effect.

The close proximity of esophagus to the left atrial posterior wall predisposes esophagus to thermal injury during catheter ablation for atrial fibrillation (AF). In this retrospective study, we aimed to investigate risk factors of esophageal injury (EI) caused by catheter ablation for AF. Patients who underwent first-time AF ablation from July 2013 to June 2018 were included. The esophagus was visualized by oral soluble contrast during ablation for all patients and a subset of patients were selected to undergo endoscopic ultrasonography (EUS) to estimate EI post ablation. Degree of EI was categorized as Kansas City classification: type 1: erythema; type 2: ulcers (2a: superficial ulcers; 2b: deep ulcers); type 3: perforation (3a: perforation without communication with the atria; 3b: atrioesophageal fistula [AEF]). Of 3,852 patients, 236 patients (61.5 ± 9.7 years; male, 69%) received EUS (EUS group) and 3616 (63.2 ± 10.9 years; male, 61.1%) without EUS (No-EUS group). In EUS group, EI occurred in 63 patients (type 1 EI in 35 and type 2 EI in 28), and no type 3 EI was observed during follow up. In a multivariable logistic regression analysis, an overlap between the ablation lesion and esophagus was an independent predictor of EI (odds ratio, 21.2; 95% CI: 6.23–72.0; P

A dual-frequency (105/140 GHz) MW-level continuous-wave gyrotron was developed for fusion application at Institute of Applied Electronics, China Academy of Engineering Physics. This gyrotron employs a cylindrical cavity working in the TE18,7 mode at 105 GHz and the TE24,9 mode at 140 GHz. A triode magnetron injection gun and a built-in quasi-optical mode converter were designed to operate at these two frequencies. For the proof-test phase, the gyrotron was equipped with a single-disk boron nitride window to achieve radio frequency output with a power of ∼500 kW for a short-pulse duration. In the preliminary short-pulse proof-test in the first quarter of 2021, the dual-frequency gyrotron achieved output powers of 300 kW at 105 GHz and 540 kW at 140 GHz, respectively, under 5 Hz 1 ms continuous pulse-burst operations. Power upgrade and pulse-width extension were hampered by the limitation of the high-voltage power supply and output window. This gyrotron design was preliminarily validated.

Non-small-cell lung cancer (NSCLC) accounts for most lung cancer cases. Therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. The proteasome system has been demonstrated clinically as a potent therapeutic target for haematological cancers. However, promising preclinical data in solid tumors are yet to be confirmed in clinics. Herein, the combinational use of Bortezomib (BZM) and 2-aminoethoxydiphenylborane (2-APB) toward NSCLC cells was studied. We confirmed that BZM-triggered cytoprotective autophagy that may counteract with the cytotoxic effects of the drug per se. 2-APB was selected from screening of a commercial natural compounds library, which potentiated BZM-induced cytotoxicity. Such an enhancement effect was associated with 2-APB-mediated autophagy inhibition. In addition, we revealed that 2-APB suppressed calcium-induced autophagy in H1975 and A549 NSCLC cells. Interestingly, BZM [0.3 mg/kg/3 days] combined with 2-APB [2 mg/kg/day] significantly inhibited both primary (around 47% tumor growth) and metastatic Lewis lung carcinoma after a 20-day treatment. Our results suggested that BZM and 2-APB combination therapy can potentially be developed as a novel formulation for lung cancer treatment.

Background/Aims: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. Methods: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry. Mcl1 and Bcl-2 expression were measured by quantitative real-time PCR and western blotting. JNK expression were measured by western blotting and flow cytometry. The in vivo role of IL-33 in RCC tumorigenesis was examined by animal models. Results: We found that increased expression of IL-33 in RCC was associated with tumor-lymph node-metastasis (TNM) stage and inversely correlated with prognosis. IL-33 enhances RCC cell growth in vivo and stimulates RCC cell proliferation and prevents chemotherapy-induced tumor apoptosis in vitro. Furthermore, we demonstrated that IL-33 promotes RCC cell proliferation and chemotherapy resistance via its receptor ST2 and the JNK signaling activation in tumor cells. Conclusion: Our findings suggest that targeting IL-33/ST2 and JNK signaling may have potential value in the treatment of RCC.

Regarding the published researches on bicycles, they fail to design fatigue characteristics of the bicycle. In addition, dynamics and fatigue characteristics are not further improved by using advanced optimization algorithms. Aiming at these questions, this paper tries to optimize dynamics and fatigue characteristics of the bicycle through combining finite element model with advanced algorithms. The advanced algorithm applies ideas of cellular automation (CA) to Particle Swarm Optimization (PSO), and then a hybrid CA-PSO algorithm is proposed. Moreover, the finite element model is also validated by experimental test. Computational results show that: the maximum stress of bicycles is mainly distributed on the frame, especially on joints of different round pipes at different moments mainly because a dead corner is at the joint, and the dead corner can easily cause stress concentration. Under alternating forces, the stress concentration at joints will cause fatigue damage. Therefore, the service life of this position will be the shortest. As a result, the dynamics and fatigue characteristics of the joint position are taken as the optimized objective. In order to verify the optimized effectiveness of the proposed CA-PSO algorithm in the paper, the widely used PSO algorithm and PSO-GA algorithm are also used to optimize the bicycle. When the traditional PSO algorithm is used to optimize the bicycle, the root-mean-square value and maximum difference of vibration accelerations are decreased by 11.9 % and 14.3 %. When the PSO-GA algorithm is used to optimize the bicycle, the root-mean-square value and maximum difference of vibration accelerations are decreased by 20.3 % and 12.9 %. When the proposed CA-PSO algorithm is used to optimize the bicycle, the root-mean-square value and maximum difference of vibration accelerations are decreased by 27.1 % and 18.6 %. Compared with other two kinds of PSO algorithms, optimized effects of vibration accelerations are very obvious. In addition, the fatigue life of the original structure is 5 years, while the fatigue life of the optimized bicycle is 7 years. Therefore, the fatigue life is improved obviously.

// Guo Wu 1 , Zhonghu Li 1 , Peng Jiang 1 , Xi Zhang 1 , Yingqiang Xu 1 , Kai Chen 1 and Xiaowu Li 1 1 Department of Hepatobiliary Surgery Institute, South Western Hospital, Third Military Medical University, Chongqing 400038, China Correspondence to: Xiaowu Li, email: lixw1966@163.com Keywords: microRNA-23a (miR-23a), pancreatic cancer, ESRP1, epithelial-mesenchymal transition (EMT), TGF-β1 Received: November 23, 2016 Accepted: May 29, 2017 Published: August 24, 2017 ABSTRACT miR-23a plays vital roles in various cancer metastases. Here, we found that miR-23a expression was significantly up-regulated in pancreatic cancer tissues compared with adjacent normal tissues. miR-23a up-regulation was significantly associated with differentiated degree, lymphoid nodal status, tumor invasion and poor survival rate in pancreatic cancer patients. We also found that miR-23a expression was significantly up-regulated in lymph node metastatic tissues and in pancreatic cancer cells that underwent epithelial-mesenchymal transition (EMT). miR-23a down-regulation blocked TGF-β1-induced EMT and reversed the phenotype of EMT in Panc-1 cells. Furthermore, miR-23a down-regulation inhibited Panc-1 cells migration and invasion in vitro and liver metastases in vivo . But the effect of miR-23a up-regulation in Aspc-1 cells was opposite to that of miR-23a down-regulation in Panc-1 cells. Epithelial splicing regulatory protein 1 (ESRP1) was identified as a direct target of miR-23a. Restoration of ESRP1 rescued the effect of miR-23a on pancreatic cancer cell progression. Moreover, miR-23a up-regulation in Aspc-1 cells induced a shift in CD44 expression from variant isoforms (CD44v) to the standard isoform (CD44s) together with increased FGFR2 IIIc mRNA levels, and decreased FGFR2 IIIb expression during EMT. But the effect of miR-23a down-regulation in Panc-1 cells was opposite to that of miR-23a up-regulation in Aspc-1 cells. In addition, the effect of miR-23a up-regulation was partly reversed by ESRP1 over-expression. Taken together, our findings indicated that miR-23a functions as an oncogene by regulating ESRP1 in pancreatic cancer.