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Background: Few studies have explored the genetic changes and clinicopathological features of stage II/III gastric cancer (GC) patients with no tumor recurrence, early recurrence, or late recurrence after curative surgery., Methods: In this study, 376 patients who underwent curative surgery for stage II/III GC were analyzed. The clinical and genetic features of patients with no recurrence, early recurrence (<2 years), and late recurrence (≥2 years) were compared., Results: Among the 376 patients, 155 experienced tumor recurrence, including 116 with early recurrence and 39 with late recurrence. Patients with early recurrence had larger tumors, fewer superficial tumors, increased lymphovascular invasion, advanced T and N categories, higher TNM stages, and poorer 5-year survival (3.4% vs. 38.5% vs. 63.5%, p <0.001) than those with late recurrence or no recurrence. For intestinal-type GC, patients with early recurrence had more MSI-H tumors than those with late recurrence or no recurrence. For diffuse-type or node-positive GC, patients with early recurrence had more PIK3CA amplifications than did those with late recurrence or with no recurrence. Peritoneal dissemination and lung metastasis were associated with PIK3CA amplifications, whereas liver metastasis was associated with larger numbers of MSI-H tumors and PI3K / Akt pathway mutations. Multivariate analysis revealed that age, tumor recurrence, and pathological T and N categories were independent prognostic factors for both overall survival and disease-free survival., Conclusion: Distinct clinical features and genetic alterations were observed in specific groups of stage II/III GC patients with differences in time to recurrence and recurrence patterns, and targeted therapy and immunotherapy may benefit these groups of patients., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: The active travel concept has gained recognition as an effective method to enhance physical activity in children's everyday mobility. Yet, there is a notable gap of quantitative evidence on its direct impacts, especially regarding physiological outcomes that can concretely demonstrate its influences on physical intensity and overall health of children., Methods: This study investigates the effects of active travel on children, focusing on trip-level physiological responses, specifically heart rate. Through a mixed survey design, we obtained a repeated-measures dataset from a cohort of 73 children (average age 13) across three Austrian secondary schools, each observed for 7 days. By applying mixed effects modelling approach, both fixed and random effects to children's heart rates were explored., Results: According to results from developed mixed linear models (maximum R 2  = 0.22), it revealed a significant positive association between active travel mode(s) engagement and heightened physiological responses (Low, Medium and High active level of trip compare to None: β = 1.81, 5.01 and 8.34, t-value = 4.70, 10.29 and 21.34), indicating that increased usage of active travel modes led to elevated heart rate values. Additionally, subjective perceptions also played an important role in influencing children's physiological responses. Feelings of exhausted, anxiety, and stress contributing to a higher heart rate (β = 14.79, 16.69 and 1.99, t-value = 20.42, 5.67 and 3.0), while unhappiness was associated with a lower heart rate (β = -5.96, t-value = -14.62). Effects of social interactions were also found during the trip. The presence of adults was associated with a calming effect (β = -1.92, t-value = -5.72), whereas solo travel resulted in lower heart rate compared to travel with peers (β = -1.95, t-value = -6.59)., Conclusion: Our article innovatively employs mixed survey methods and heart rate data to quantitatively demonstrate the positive association between engagement in active travel modes and heightened physiological responses in children, elucidating the intricate interplay of subjective perceptions and social interactions during trips, thus offering valuable insights into the health implications of active travel at a trip level. Future research will keep on leveraging survey and experimental methods., Competing Interests: Declarations Ethical approval for conducting the study was obtained from the University of Natural Resources and Life Sciences Ethics Committee (Reference number: BOKU- 2023/008). Written informed consent was obtained from the school principal and participants’ parents/guardians. Principal/parent/child refusal to participate was excluded from the study. The assent was obtained from all participants after adequately informing them of any study inconvenience and their right to withdraw without prejudice at any stage during the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Long non-coding RNAs (lncRNAs) primarily engage with mRNA, DNA, proteins, and microRNAs (miRNAs), thereby regulating gene expression; however, its specific role in diabetic erectile dysfunction (DED) has not been studied. This study aims to investigate the effects and mechanisms of LncRNA CRYM-AS1 in DED. The differential target gene LncRNA CRYM-AS1 was identified in the penile tissues of rats with DED through bioinformatics analyses. A KEGG signaling pathway enrichment analysis suggested a potential association between LncRNA CRYM-AS1 and the Hippo-YAP1 pathway. Real-time fluorescent quantitative PCR (RT-qPCR) results indicated a significantly lower expression of LncRNA CRYM-AS1 in the penile tissue of DED rats compared to the control group. Western Blot and immunohistochemistry (IHC) staining results demonstrated significantly elevated protein expression levels of YAP1, Caspase3, BAX, and Bcl-2, with a decreased Bcl-2/BAX ratio. CCK8 cell viability results showed a significant decrease in cell viability in the high glucose group at 4 days of modeling, and compared with the normal glucose group, RT-qPCR results showed that the expression of LncRNA CRYM-AS1 in the high glucose group in human umbilical vein endothelial cells (HUVECs) was significantly reduced; Western Blot results showed that the protein expression of YAP1, Cleaved-caspase3 and BAX was significantly up-regulated, and the protein expression of Bcl-2 was significantly down-regulated in the high glucose group. Compared with the empty vector group, RT-qPCR results after transfection of si LncRNA CRYM-AS1 showed that the expression of LncRNA CRYM-AS1 was down-regulated, the mRNA and protein expression of YAP1, Caspase3, Cleaved-caspase3, BAX, and Bcl-2 were significantly up-regulated, and the Bcl-2/BAX ratio decreased. Flow cytometry results showed that the apoptosis rate of HUVECs increased after interference. Low expression of LncRNA CRYM-AS1 may activate the Hippo-YAP1 signaling pathway to regulate apoptosis in HUVECs, leading to ED development, and the discovery of new target genes may provide new therapeutic targets to regulate diabetic erectile disfunction., Competing Interests: None., (AJCEU Copyright © 2024.)

This article investigates the extended dissipative finite-time boundedness (ED-FTB) problem for fuzzy switched systems under deception attacks. To improve the network resource efficiency, a multidomain probabilistic event-triggered mechanism (MDPETM) is proposed. The mode mismatched phenomenon is modeled based on the switching delay information between the controller mode and the system mode. To extract the true signal generated by the MDPETM, a virtual delay concept is developed. The constraint that the controller and the system must have the same premise variables is removed. Based on the MDPETM, mismatched fuzzy state feedback controllers are first devised which may not share the same modes with the system. Then, by establishing fuzzy basis and controller mode-dependent Lyapunov functionals, sufficient criteria free of nonlinear terms existing in the literature are derived, which ensure the ED-FTB of the closed-loop system under admissible delays and deception attacks. Finally, an application-oriented one-link robotic arm system is utilized to validate the theoretical results.

In this study, asynchronous sliding-mode control (SMC) for discrete-time networked hidden stochastic jump systems subjected to the semi-Markov kernel (SMK) and cyber attacks is investigated. Considering the statistical characteristic of the SMK, which is challenging to acquire in engineering, this study recognizes the SMK to be incomplete. Due to the mode mismatch between the original system and the control law in the operating process, a hidden semi-Markov model is proposed to describe the considered asynchronous situation. The main aim of this study is to construct an asynchronous SMC mechanism based on an incomplete SMK framework under the condition of random denial-of-service attacks so that the resulting closed-loop system can realize the mean-square stability. By virtue of the upper bound of the sojourn time in each mode, innovative techniques are developed for mean-square stability analysis under an incomplete SMK. Furthermore, an asynchronous SMC scheme is designed to achieve the reachability of the quasi-sliding mode. Finally, the effectiveness is verified using an electronic throttle model.

A slow time-delay assumption restricts the application of control approaches for numerous systems which are constantly affected by multiple uncertainties, including parameters, control coefficients, and the asymmetric dead-zone input. This work presents a new adaptive method for a class of high-order nonlinear delayed systems by removing the so-called slow time-delay assumption and multiple uncertainties. Remarkably, with a novel Lyapunov-Razumikhin (L-R) function and a direct fuzzy adaptive regulation scheme, a memoryless adaptive feedback controller is skillfully constructed to guarantee that the output tracks the given reference signal while keeping the boundedness of all closed-system signals. Finally, the presented scheme is applied to control a single-link robot system.

This study reports a fixed-time tracking control problem for strict-feedback nonlinear systems with quantized inputs and actuator faults where the total number of faults is allowed to be infinite. By taking advantage of radial basis function neural networks (RBFNNs), unknown nonlinear function terms in the system dynamic model can be effectively approached. In addition, based on the sector property of quantization nonlinearities and the structure of the actuator fault model, novel adaptive estimations and innovative auxiliary design signals are constructed to compensate for the influence caused by actuator faults and quantized inputs properly in the fixed-time convergence settings. Then, rigorous theoretical analysis manifests that the proposed control scheme can make the output tracking error converge to a small neighborhood of the origin within a fixed time, and the upper bound of the setting time not only does not depend on initial states of the system but also can be preassigned by selecting parameters appropriately. Meanwhile, all the signals in the closed-loop system remain bounded. Finally, a numerical example and a practical example of a single-link manipulator are presented to demonstrate the effectiveness of the proposed control algorithm.

This article investigates robust predictive control problem for unknown dynamical systems. Since the dynamics unavailability restricts feasibility of model-driven methods, learning robust predictive control (LRPC) framework is developed from the aspect of time consistency. Under feedback-like control causality, the robust predictive control is then reconstructed as spatialbKKtemporal games, and we guarantee stability through time-consistent Nash equilibrium. For gradation clarity, our framework is specified as four-follow contents. First, multistep feedback-like control causality is drawn from time series analysis, and Takens' theorem provides theoretical support from steady-state property. Second, control problem is reconstructed as games, while performance and robustness partition the game into temporal nonzero-sum subgames and spatial zero-sum ones, respectively. Next, multistep reinforcement learning (RL) is designed to solve robust predictive control without system model. Convergence is proven through bounds analysis of oscillatory value functions, and properties of receding horizon are derived from time consistency. Finally, data-driven implementation is given with function approximation, and neural networks are chosen to approximate value functions and feedback-like causality. Weights are estimated with least squares errors. Numerical results verify the effectiveness.

Accurate and efficient extraction of tree parameters from plantations lay foundation for estimating individual wood volume and stand stocking. In this study, we proposed a method of extracting high-precision tree parameters based on airborne LiDAR data. The main process included data pre-processing, ground filtering, individual tree segmentation, and parameter extraction. We collected high-density airborne point cloud data from the large-diameter timber of Fokienia hodginsii plantation in Guanzhuang State Forestry Farm, Shaxian County, Fujian Province, and pre-processed the point cloud data by denoising, resampling and normalization. The vegetation point clouds and ground point clouds were separated by the Cloth Simulation Filter (CSF). The former data were interpolated using the Delaunay triangulation mesh method to generate a digital surface model (DSM), while the latter data were interpolated using the Inverse Distance Weighted to generate a digital elevation model (DEM). After that, we obtained the canopy height model (CHM) through the difference operation between the two, and analyzed the CHM with varying resolutions by the watershed algorithm on the accuracy of individual tree segmentation and parameter extraction. We used the point cloud distance clustering algorithm to segment the normalized vegetation point cloud into individual trees, and analyzed the effects of different distance thresholds on the accuracy of indivi-dual tree segmentation and parameter extraction. The results showed that the watershed algorithm for extracting tree height of 0.3 m resolution CHM had highest comprehensive evaluation index of 91.1% for individual tree segmentation and superior accuracy with R 2 of 0.967 and RMSE of 0.890 m. When the spacing threshold of the point cloud segmentation algorithm was the average crown diameter, the highest comprehensive evaluation index of 91.3% for individual tree segmentation, the extraction accuracy of the crown diameter was superior, with R 2 of 0.937 and RMSE of 0.418 m. Tree height, crown diameter, tree density, and spatial distribution of trees were estimated. There were 5994 F. hodginsii , with an average tree height of 16.63 m and crown diameter of 3.98 m. Trees with height of 15-20 m were the most numerous (a total of 2661), followed by those between 10-15 m. This method of forest parameter extraction was useful for monitoring and managing plantations.

This article addresses the practically predefined-time adaptive fuzzy tracking control problem of strict-feedback nonlinear stochastic systems, where the system under consideration includes stochastic disturbances and uncertain parameters. First, in this study, practically predefined-time stochastic stabilization (PPSS) in the p th moment sense is introduced, and a Lyapunov-type criterion for PPSS is proposed to assure the stabilization of the system considered. With these ideas, based on the backstepping design method, a semiglobally practically predefined-time adaptive fuzzy tracking control algorithm is proposed with a fuzzy system used to approximate the unknown part of the system. Moreover, the settling time of the system response can be arbitrarily adjusted in a mean-value sense, and such freedom can be used to improve the stochastic finite-/fixed-time control results. Finally, a practical example and a numerical example of a comparison are provided to validate the effectiveness of the proposed control strategy.

This article focuses on the mean-field linear-quadratic Pareto (MF-LQP) optimal strategy design for stochastic systems in infinite horizon, which is with the H ∞ constraint when the system is disturbed by external interferences. The stochastic bounded real lemma (SBRL) with any initial state in infinite horizon is first investigated based on the stabilizing solution of the generalized algebraic Riccati equation (GARE). Then, by discussing the convexity of the cost functional, the stochastic indefinite MF-LQP control problem is defined and solved based on the MF-LQ theory and Pareto theory. When the worst case disturbance is considered in the collaborative multiplayer system, we show that the Pareto optimal strategy design with H ∞ constraint [or robust Pareto optimal strategy, (RPOS)] can be given via solving two coupled GAREs. When the worst case disturbance and the Pareto efficient strategy work, all Pareto solutions are obtained by a generalized Lyapunov equation. Finally, a practical example shows that the obtained results are effective.

The event-triggered sliding-mode control (SMC) for discrete-time networked Markov jumping systems (MJSs) with channel fading is investigated by means of a genetic algorithm. In order to reduce resource consumption in the transmission process, an event-triggered protocol is adopted for networked MJSs. A key feature is that the signal transmission is inevitably affected by fading phenomenon due to delay, random noise, and amplitude attenuation in a networked environment. With the aid of a common sliding surface, an event-triggered SMC law is designed by adjusting the system network mode. Under the framework of stochastic Lyapunov stability, sufficient conditions are constructed to ensure the mean-square stability of the closed-loop networked MJSs, and the sliding region is reached around the specified sliding surface. Moreover, based on the iteration optimizing accessibility of objective function, an effective SMC approach under genetic algorithm is proposed to minimize the convergence region around the sliding surface. Finally, the effectiveness of the proposed method is proved by the F-404 aircraft model.

Nonsmooth nonlinear systems can model many practical processes with discontinuous property and are difficult to be stabilized by classical control methods like smooth nonlinear systems. This article considers the output-feedback adaptive neural network (NN) control problem for nonsmooth nonlinear systems with input deadzone and saturation. First, the nonsmooth input deadzone and saturation is converted to a smooth function of affine form with bounded estimation error by means of the mean-value theorem. Second, with the help of approximation theorem and Filippov's differential inclusion theory, the given nonsmooth system is converted to an equivalent smooth system model. Then, by introducing a proper logarithmic barrier Lyapunov function (BLF), an output-feedback adaptive NN strategy is set up by constructing an appropriate observer and adopting the adaptive backstepping technique. A new stability criterion is established to guarantee that all the signals in the closed-loop system are semiglobally uniformly ultimately bounded (SGUUB). Finally, comparative simulations through Chua's oscillator are offered to verify the effectiveness of the proposed control algorithm.

Background: Gastrectomy remains the curative option in gastric cancer. However, the growing concern that preoperative waiting jeopardizes survival has not been fully addressed. The present population-based cohort study aimed to clarify the impact of preoperative waiting time (PreWT)., Methods: We included patients with clinical Stage II-III gastric cancer who received curative surgery from 2008 to 2017 of Taiwan Cancer Registry. PreWT was defined as the time from endoscopic diagnosis to surgery. The prognostic impact on overall survival (OS) was evaluated with Cox and restricted cubic spline regressions., Results: A total of 3059 patients with a median age of 68 years were evaluated. The median PreWT was 16 days (interquartile range, 11-24 days), and patients with a shorter PreWT were younger, had a more advanced disease and received adjuvant therapies. Despite a shorter OS occurring with prolonged PreWT (median OS by PreWT [days]: 7-13, 2.7 years; 14-20, 3.1 years; 21-27, 3.0 years; 28-34, 4.7 years; 35-31, 3.7 years; 42-48, 3.4 years; 49-118, 2.8 years; p = 0.029), the differences were not significant after adjustment. The Cox and restricted cubic spline regressions showed that prolonged PreWT was not a significant prognostic factor for OS (p = 0.719)., Conclusions: The population-based study suggests that a PreWT of 49-118 days does not independently correlate with a poor prognosis in Stage II-III gastric cancer. The study provides rationale for a window period for preoperative therapies and patient optimization., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

This study mainly concentrates on adaptive asymptotic tracking control for input-quantized strict-feedback nonlinear systems subjected to multiple unknown control directions. Novel improved lemmas, which relax the conditions for handling unknown control coefficients in the existing theoretical results, are certificated that can be applied to resolve the tracking problem for nonlinear systems under input quantification and unknown control directions simultaneously. Furthermore, by incorporating positive integral time-varying functions and the disintegration of the hysteresis quantizer into the controller design, the asymptotic tracking control is successfully achieved. Moreover, all signals in the closed-loop system are guaranteed to be bounded. Ultimately, a comparing numerical simulation and a practical simulation of a Nomoto ship model are presented to validate the feasibility of the proposed control algorithm.

Objective: The modified day surgery procedure was compared with traditional inpatient procedure and standard day surgery procedure of concealed penile surgery to investigate its advantages, as well as the feasibility of promoting it in our country., Methods: Retrospective analyzing the clinical data between 135 cases of the concealed penis in children who underwent modified day surgery (day group) and 101 cases who underwent hospitalization surgery (hospitalization group) at the Second Hospital of Hebei Medical University and the results of follow-up.The modified day surgery procedure involves the establishment of dedicated day wards in each surgical department, where the patient's condition is monitored until 8 o'clock the following morning to assess their discharge eligibility.The children's clinical data was divided into two groups to compare clinical parameters, including age at surgery, bleeding volume, operation time, hospitalization expenses, day of hospitalization, and the occurrence of short-term complications before the initial dressing change after surgery.The satisfaction survey of the children was conducted among three distinct groups: the modified day group, the standard day group, and the hospitalization group enabling a comparison of satisfaction levels among these groups., Results: The mean ages of the inpatient and day surgery groups were 8.92±4.42 years old and 11.85±4.43 years old, respectively. No significant differences were observed between these two groups regarding operation time, bleeding volume, and postoperative complications (P>0.05). Compared to the inpatient group, the mean inpatient time and the hospitalization cost of the day group decreased by 69% and 27%, respectively (P<0.05). The patients in the modified procedure group reported the highest satisfaction among the three groups., Conclusion: Modified day surgery procedure offers advantages over the standard day surgery procedure and traditional inpatient surgical procedures for the operative treatment of the concealed penis, which makes it suitable for large-scale popularization in China.

The finite-time event-triggered stabilization is studied for a class of discrete-time nonlinear Markov jump singularly perturbed models with partially unknown transition probabilities (TPs). T-S fuzzy strategy is adopted to characterize the related nonlinear Markov jump singularly perturbed models. The control objective is to make sure that the system states remain within a bounded domain during a fixed-time interval. First, a mode-dependent event-triggered scheme is constructed to reduce the communication burden and save the network bandwidth. On that basis, by using a new Lyapunov function, a developed finite-time stability criterion is derived for the corresponding system to avoid an ill-conditioned issue due to a small singular perturbation parameter. Moreover, the mode-dependent fuzzy controller gain and the event-triggered parameter are co-designed under the framework of partially unknown TPs. Finally, the feasibility of the main results is provided to verify the finite-time event-triggered control strategy.

Background: Predicting the resistance profiles of antimicrobial resistance (AMR) pathogens is becoming more and more important in treating infectious diseases. Various attempts have been made to build machine learning models to classify resistant or susceptible pathogens based on either known antimicrobial resistance genes or the entire gene set. However, the phenotypic annotations are translated from minimum inhibitory concentration (MIC), which is the lowest concentration of antibiotic drugs in inhibiting certain pathogenic strains. Since the MIC breakpoints that classify a strain to be resistant or susceptible to specific antibiotic drug may be revised by governing institutes, we refrained from translating these MIC values into the categories "susceptible" or "resistant" but instead attempted to predict the MIC values using machine learning approaches. Results: By applying a machine learning feature selection approach on a Salmonella enterica pan-genome, in which the protein sequences were clustered to identify highly similar gene families, we showed that the selected features (genes) performed better than known AMR genes, and that models built on the selected genes achieved very accurate MIC prediction. Functional analysis revealed that about half of the selected genes were annotated as hypothetical proteins (i.e., with unknown functional roles), and that only a small portion of known AMR genes were among the selected genes, indicating that applying feature selection on the entire gene set has the potential of uncovering novel genes that may be associated with and may contribute to pathogenic antimicrobial resistances. Conclusion: The application of the pan-genome-based machine learning approach was indeed capable of predicting MIC values with very high accuracy. The feature selection process may also identify novel AMR genes for inferring bacterial antimicrobial resistance phenotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Su and Wu.)

This study concentrates on the tracking control problem for nonlinear systems subject to actuator saturation. To improve the performance of the controller, we propose a fixed-time tracking control scheme, in which the upper bound of the convergence time is independent of the initial conditions. In the control scheme, first, a smooth nonlinear function is employed to approximate the saturation function so that the controller can be designed under the framework of backstepping. Then, the effect of input saturation is compensated by introducing an auxiliary system. Furthermore, a fixed-time adaptive neural network control method is given with the help of fixed-time control theory, in which the dynamic order of controllers is reduced to a certain extent since there is only one updating law in the entire control design. Through rigorous theoretical analysis, it is concluded that the proposed control scheme can guarantee that: 1) the output tracking error can converge to a small neighborhood near the origin in a fixed time and 2) all signals in the closed-loop system are bounded. Finally, a numerical example and a practical example based on the single-link manipulator are provided to verify the effectiveness of the proposed method.

In this study, a graph regularized algorithm for early expression detection (EED), called GraphEED, is proposed. EED is aimed at detecting the specified expression in the early stage of a video. Existing EED detectors fail to explicitly exploit the local geometrical structure of the data distribution, which may affect the prediction performance significantly. According to manifold learning, the data in real-world applications are likely to reside on a low-dimensional submanifold embedded in the high-dimensional ambient space. The proposed graph Laplacian consists of two parts: 1) a k -nearest neighbor graph is first constructed to encode the geometrical information under the manifold assumption and 2) the entire expressions are regarded as the must-link constraints since they all contain the complete duration information and it is shown that this can also be formulated as a graph regularization. GraphEED is to have a detection function representing these graph structures. Even with the inclusion of the graph Laplacian, the proposed GraphEED has the same computational complexity as that of the max-margin EED, which is a well-known learning-based EED, but the detection performance has been largely improved. To further make the model appropriate in large-scale applications, with the technique of online learning, the proposed GraphEED is extended to the so-called online GraphEED (OGraphEED). In OGraphEED, the buffering technique is employed to make the optimization practical by reducing the computation and storage cost. Extensive experiments on three video-based datasets have demonstrated the superiority of the proposed methods in terms of both effectiveness and efficiency.

Compared to stage I-III gastric cancer (GC), the level of cell-free DNA (cfDNA) was significantly higher in stage IV GC. The mutation patterns of different metastatic patterns between cfDNA and tumor DNA in stage IV GC have not yet been reported. We used next-generation sequencing (NGS) to analyze cfDNA and tumor DNA in 56 stage IV GC patients. Tumor DNA and cfDNA were analyzed using a 29-gene NGS panel. In tumor samples, the most commonly mutated gene was TP53 (64%), followed by ARID1A (62%), KMT2C (60%) and KMT2D (58%). In cfDNA samples, the most commonly mutated genes were FAT4 (19%) and MACF1 (19%), followed by KMT2D (18%), ARID1A (14%) and LRP1B (14%). The concordance of mutation patterns in these 29 genes was 42.0% between cfDNA and tumor DNA. A specificity of 100% was found when using the mutation status of cfDNA to predict mutations in tumor samples. The sensitivity of the mutation status of cfDNA to predict mutation in tumor samples was highest in FAT4 (88.9%), followed by MACF1 (80%), CDH1 (75%) and PLB1 (75%). For cfDNA with PLB1 mutations, patients were more likely to develop distant lymphatic metastasis than peritoneal metastasis. Patients with multiple-site metastases had significantly more mutated spots than patients with single-site metastasis. Due to the high sensitivity and specificity of some genes in the prediction of mutation in tumor samples, monitoring the mutation pattern of cfDNA may be useful in the stage IV GC treatment.

Background: To date, few reports have investigated the genetic alterations and clinicopathological features among gastric cancer (GC) patients with no tumor recurrence, early recurrence, and late recurrence following curative surgery., Methods: A total of 473 GC patients undergoing curative surgery were included. The clinicopathological characteristics, patient prognosis, recurrence patterns, and genetic alterations were compared between GC patients with early recurrence and late recurrence., Results: Among the 473 GC patients, 119 had early recurrence (<2 years) and 45 had late recurrence (≥2 years). Patients with early recurrence had tumor size larger than 5 cm, fewer superficial-type tumors, more lymphovascular invasion, more advanced pathological T and N categories and Tumor, Node, Metastasis (TNM) stages, and worse 5-year overall survival than patients with late recurrence and no recurrence. For intestinal-type GC, patients with no tumor recurrence had more Helicobacter pylori infection than patients with early recurrence and late recurrence; for diffuse-type GC patients, the frequency of PIK3CA amplification was the highest in early recurrence, followed by late recurrence and no recurrence. GC patients with single-site recurrence had more ARID1A mutations than those with multiple-site recurrence. Multivariate analysis demonstrated that age, tumor recurrence, and pathological N categories were independent prognostic factors., Conclusion: PIK3CA amplifications were more common in diffuse-type GC with early recurrence, whereas ARID1A mutations were more common in patients with single-site recurrence. Targeted therapy and immunotherapy might be helpful for these patients., Competing Interests: Conflicts of interest: Dr. Yee Chao, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

The fault detection issue is investigated for complex stochastic delayed systems in the presence of positivity constraints and semi-Markov switching parameters. By choosing a mode-dependent fault detection filter (FDF) as a residual generator, the corresponding fault detection is formulated as a positive [Formula: see text] filter problem. Attention is focused on the design of a mode-dependent FDF to minimize the error between the residual signal and the fault signal. The designed FDF features good sensitivity of the faults and robustness against the external disturbances. Subsequently, by means of the linear copositive Lyapunov functional (LCLF), stochastic stability is proposed to satisfy an expected [Formula: see text]-gain performance. Some solvability conditions for the desired mode-dependent FDF are established with the help of a linear programming approach. Finally, an application example of a data communication network model is provided to demonstrate the effectiveness of the theoretical findings.

This article focuses on the H ∞ adaptive tracking problem of uncertain switched systems. A key point of the study is to set up a multiple piecewise Lyapunov function framework which provides an effective tool for designing an adaptive switching controller consisting of a state-feedback and time-driven switching signal and a time-driven adaptive law. The proposed switching signal guarantees the solvability of the H ∞ adaptive tracking problem for uncertain switched systems. Significantly, it provides plenty of adjusting time for the adaptive tracking control strategy to damp the transient caused by switching and avoids frequent switching. A novel time-driven adaptive switching controller is established such that the tracking error asymptotically converges to zero and all the signals in the error dynamic system are bounded under an achieved disturbance attenuation level. The solvability criterion ensuring an H ∞ adaptive tracking performance is established for the uncertain switched systems, where the solvability of the H ∞ adaptive tracking problem for individual subsystems is not required. Finally, the proposed method is applied to the electro-hydraulic unit.

The issue of adaptive output-feedback stabilization is investigated for a category of stochastic nonstrict-feedback nonlinear systems subject to unmeasured state and unknown control directions. By combining the event-triggered mechanism and backstepping technology, an adaptive fuzzy output-feedback controller is devised. In order to make the controller design feasible, a linear state transformation is introduced into the initial system. At the same time, the Nussbaum function technology is used to overcome the difficulties caused by unknown control directions, and the state observer solves the problem of the unmeasured state. Based on the fuzzy-logic system and its structural characteristics, the issue of unknown nonlinear function with nonstrict-feedback structure in the system is tackled. The designed controller could not only guarantee all signals of closed-loop systems are bounded in probability but also save communication resources effectively. Finally, numerical simulation and ship dynamics example are given to confirm the effectiveness of the proposed method.

Background: Sitosterolemia is a rare recessive genetic abnormality of hyperlipidemia; it is characterized by increased levels and accumulation of sitosterol in the plasma and local tissues., Case Descriptions: The study subjects were two siblings (brother and sister) who had sitosterolemia with systemic multiple xanthomas as the main manifestation. The main clinical manifestations were hypercholesterolemia, premature atherosclerosis, arrhythmia, systemic multiple xanthomas, etc. After genetic testing, it was found that the patients had a compound heterozygous mutation of c.1324+1de1G in exon 7 and exon 9 of chromosome 2p21 of the adenosine triphosphate binding cassette transporter G family member 5(ABCG5) gene; the mutation at c.904+1G>A was of maternal origin, and the mutation at c. 1324+1de1G was of paternal origin. The compound heterozygous mutation of these two genes led to a metabolic disorder of plant sterols in vivo ., Conclusion: Sitosterolemia is an autosomal recessive disease that could be effectively controlled after dietary control and oral lipid-lowering therapy with Ezetimibe. Xanthomas, which affects function and appearance, could be surgically removed, and primary wound healing could be achieved., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Su, Xiong, Ding, Kuang and Lin.)

This article studies the finite-time tracking control problem for the single-link flexible-joint robot system with actuator failures and proposes an adaptive fuzzy fault-tolerant control strategy. More precisely, the issue of "explosion of complexity" is successfully solved by incorporating the command filtering technology and the backstepping method. The unknown nonlinearities are identified with the help of the fuzzy logic system. An event-triggered mechanism with the relative threshold strategy is exploited to save communication resources. Furthermore, the proposed control design can guarantee that the tracking error converges to a small neighborhood of origin within a finite time by taking full advantage of the finite-time stability theory. Finally, the simulation example is presented to further verify the validity of the proposed control method.

This article focuses on global finite-time output feedback stabilization for uncertain nonlinear systems with unknown measurement sensitivity. The existence of the continuous measurement error resulting from limited accuracy of sensors invalidates the existing design strategies depending on the use of the precise output in the construction of an observer, which highlights the contribution of this article. Essentially, different from related works, we propose a new finite-time convergent observer by avoiding the use of the information on nonlinearities. By combining the homogeneous domination with the addition of a power integrator method, an output feedback controller composed of multiple nested sign functions is successfully developed. Finally, the effectiveness of the presented scheme is exhibited by a numerical example.

Background/purpose: Previous studies have seldom investigated the psychological factors that are associated with dissatisfaction with healthcare services. We therefore examined the associations of depression and anxiety with service dissatisfaction among older adults., Methods: A community-based health survey was conducted from 2012 to 2016. Residents aged ≥65 years were randomly recruited from Yilan City, Taiwan. Besides overall dissatisfaction, we assessed dissatisfaction with physicians' ability, physicians' attitude, and waiting time. The Hospital Anxiety and Depression Scale was used to detect depressive and anxiety symptoms with optimal cut-off points of 3 for the anxiety subscale and 6 for the depression subscales., Results: Of the 3480 residents included in this study, the overall dissatisfaction rate was 7.9%. After controlling for covariates, depressive and anxiety symptoms were consistently correlated with the various dimensions of dissatisfaction. More specifically, depressive symptoms were associated with overall dissatisfaction and dissatisfaction with physicians' ability and attitude. Conversely, anxiety was uniquely associated with dissatisfaction with waiting time., Conclusion: Psychological symptoms were consistent correlates of dissatisfaction with healthcare services among older adults, although the specific symptoms had different associations with the various dimensions of dissatisfaction., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

This article focuses on the design of a novel adaptive fuzzy event-triggered tracking control approach for a category of high-order uncertain nonlinear systems with prescribed performance requirements, in which a high-order tan-type barrier Lyapunov function (BLF) is employed to handle and analyze the output tracking error, fuzzy systems are adopted to identify the totally unknown nonlinear functions, and only one gain function rather than parameter estimation functions is designed to cancel out all unknowns appearing in fuzzy systems. As a result, complicated calculations are avoided and a structured simple control is achieved. The proposed controller not only ensures that the tracking error is always within a predefined region but also reduces the communication burden from the controller to the actuator. Finally, comparison simulations are presented to verify the effectiveness of the proposed control schemes.

This article investigates the H ∞ stochastic tracking control problem for uncertain fuzzy Markovian hybrid switching systems by using a fuzzy switching dynamic adaptive control approach. The long and the short is to construct multiple piecewise stochastic Lyapunov functions which provide an effective tool for designing hybrid switching law and fuzzy switching dynamic adaptive law. A hybrid switching law, including both stochastic switching and deterministic switching, is designed to represent more general switching scenarios, which can improve the H ∞ adaptive tracking performance through offering a running time before stochastic switching for the adaptive control strategy to work well. A fuzzy switching dynamic adaptive control technique is developed such that all signals of the tracking error equation are bounded, and the system state trajectory tracks the reference model state trajectory under a disturbance attenuation level as closely as possible. Finally, an application study verifies the effectiveness of the acquired methods.

γ-Lactams form important structural cores of a range of medicinally relevant natural products and clinical drugs, principal examples being the new generation of immunomodulatory imide drugs (IMiDs) and the brivaracetam family. Compared to conventional multistep synthesis, an intramolecular γ-C-H amination of aliphatic amides would allow for the direct construction of valuable γ-lactam motifs from abundant amino acid precursors. Herein we report a novel 2-pyridone ligand enabled Pd(II)-catalyzed γ-C(sp 3 )-H lactamization of amino acid derived native amides, providing the convenient synthesis of γ-lactams, isoindolinones, and 2-imidazolidinones. C6-Substitution of the 2-pyridone ligand is crucial for the lactam formation. This protocol features the use of N -acyl amino acids, which serve as both the directing group and cyclization partner, practical and environmentally benign tert -butyl hydrogen peroxide (TBHP) as the sole bystanding oxidant, and a broad substrate scope. The utility of this protocol was demonstrated through the two-step syntheses of a lenalidomide analog and brivaracetam from readily available carboxylic acids and amino acids.

Urinary incontinence (UI) is a common problem affecting older adult women globally, but studies regarding combined treatments for all types of UI are still lacking. Here we evaluate the efficacy of a comprehensive rehabilitation program for women with UI. A comprehensive rehabilitation program was introduced that combines pelvic floor muscle (PFM) exercises, functional electrical stimulation, and timely biofeedback during the training process. Data of patients with stress (SUI), urgency (UUI), or mixed (MUI) urinary incontinence who participated in this program between 2016 and 2019 were reviewed retrospectively. Seventy-three subjects (mean age 59.2 ± 12.7 years) were enrolled. After 12 weeks of rehabilitation, vaginal pressure and control accuracy increased in all groups. PFM maximum recruitment increased significantly at week 12 in SUI and UUI, but not in MUI. At week 6, only the SUI group had achieved significant improvements in vaginal pressure, PFM maximum recruitment and control accuracy. The Short-form Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7) scores declined dramatically after the program started, and significant improvements were maintained to week 48. The comprehensive rehabilitation program is effective and decreases urinary leakage episodes and improves quality of life in women with UI, especially SUI.

Chemotherapy is generally considered as the main treatment for metastatic gastric adenocarcinoma. The role of gastrectomy for metastatic gastric cancer without obvious symptoms is controversial. The objective of this study is to investigate survival outcomes of treatment modalities using a real-world data setting. A retrospective cohort study was designed using the Taiwan Cancer Registry database. We identified the treatment modalities and used Kaplan-Meier estimates and Cox regressions to compare patient survival outcomes. From 2008 to 2015, 5599 gastric adenocarcinoma patients were diagnosed with metastatic disease (M1). The median overall survival (OS) of patients with surgery plus chemotherapy had the longest survival of 14.2 months. The median OS of the patients who received chemotherapy alone or surgery alone was 7.0 and 3.9, respectively. Age at diagnosis, year of diagnosis, tumor grade, and treatment modalities are prognostic factors for survival. The hazard ratios for patients who received surgery plus chemotherapy, surgery alone, and supportive care were 0.47 (95% CI 0.44-0.51), 1.22 (95% CI 1.1-1.36), and 3.23 (95% CI 3.01-3.46), respectively, by multivariable Cox regression analysis when using chemotherapy alone as a referent. Chemotherapy plus surgery may have a survival benefit for some selected gastric adenocarcinoma patients with metastatic disease., (© 2021. The Author(s).)

Thyroid nodules are widespread in the United States and the rest of the world, with a prevalence ranging from 19 to 68%. The problem with nodules is whether they are malignant or benign. Ultrasonography is currently recommended as the initial modality for evaluating thyroid nodules. However, obtaining a good diagnosis from ultrasound imaging depends entirely on the radiologists levels of experience and other circumstances. There is a tremendous demand for automated and more reliable methods to screen ultrasound images more efficiently. This research proposes an efficient and quick detection deep learning approach for thyroid nodules. An open and publicly available dataset, Thyroid Digital Image Database (TDID), is used to determine the robustness of the suggested method. Each image is formatted into a pyramid tile-based data structure, which the proposed VGG-16 model evaluates to provide segmentation results for nodular detection. The proposed method adopts a top-down approach to hierarchically integrate high- and low-level features to distinguish nodules of varied sizes by employing fuse features effectively. The results demonstrated that the proposed method outperformed the U-Net model, achieving an accuracy of 99%, and was two times faster than the competitive model.

This article is to tackle the event-based state-feedback control problem for interval type-2 (IT2) fuzzy systems subject to the fading channel. For saving communication resources, a dynamic event-triggered (ET) mechanism is utilized to decide the data transmission from sensors to the controller. A time-varying random process is employed to characterize the fading phenomenon in the unpredictable communication network. By considering the effect of channel fading, a nonparallel distribution compensation (non-PDC) IT2 fuzzy controller is synthesized and its number of rules and membership functions (MFs) can be freely selected. As a consequence, the closed-loop fuzzy system possesses imperfectly matched MFs. By taking the global membership boundary information into stability analysis, the membership-function-dependent analysis method is employed to handle these imperfectly matched MFs and to obtain relaxed criteria. Besides, sufficient criteria are obtained so that the resulting closed-loop IT2 fuzzy system can achieve stochastic stability despite fading measurements. The effectiveness of the proposed method is illustrated by a mass-spring-damper system and a numerical example.

Background: Various reconstruction methods have been performed following distal gastrectomy; however, each reconstruction method has its own advantages and disadvantages. This study aims to compare the long-term outcomes between Billroth-I (B-I) and Roux-en-Y (RY) reconstruction after distal gastrectomy for gastric cancer., Methods: A total of 459 patients who underwent distal gastrectomy (B-I: 166, RY: 293) were included. Postoperative endoscopic findings and biliary tract stone formation were compared between the two groups., Results: At 1 year and 2 years postoperatively, gastric residue was more common in the RY group, gastritis was similar between groups, and bile reflux was more common in the B-I group. At 5 years postoperatively, gastric residue was similar between the groups, while gastritis and bile reflux were more common in the B-I group. Gastroesophageal reflux was more common in the B-I group at 1 year postoperatively, but gastroesophageal reflux became not significantly different between the groups at 2 and 5 years postoperatively. Gallstone formation was more common in the RY group and in patients aged ≥ 65 years., Conclusion: During long-term follow-up, RY reconstruction was associated with lower incidence of bile reflux and gastritis, and higher incidence of gallstone formation than B-I reconstruction. The incidence of gastric residue was more common in the RY reconstruction group in the early postoperative period and became not significantly different between the two groups over time. For aged patients with RY reconstruction, cholecystectomy is recommended concurrently as gastrectomy., (© 2020. The Society for Surgery of the Alimentary Tract.)

Coronary artery disease is caused primarily by vessel narrowing. Extraction of the coronary artery area from images is the preferred procedure for diagnosing coronary diseases. In this study, a U-Net-based network architecture, 3D Dense-U-Net, was adopted to perform fully automatic segmentation of the coronary artery. The network was applied to 474 coronary computed tomography (CT) angiography scans performed at Wanfang Hospital, Taiwan. Of these, 10% were used for testing. The CT scans were divided into patches of 16 original high-resolution slices. The slices were overlapped between patches to take advantage of surrounding imaging information. However, an imbalance between the foreground and background presents a challenge in smaller-object segmentation such as with coronary arteries. The network was optimized and achieved a promising result when the focal loss concept was adopted. To evaluate the accuracy of the automatic segmentation approach, the dice similarity coefficient (DSC) was calculated, and an existing clinical tool was used. The subjective ratings of three experienced radiologists were used to compare the two ratings. The results show that the proposed approach can achieve a DSC of 0.9691, which is significantly higher than other studies using a deep learning approach. In the main trunk, the results of automatic segmentation agree with those of the clinical tool; they were significantly better in some small branches. In our study, automatic segmentation tool shows high-performance detection in coronary lumen vessels, thereby providing potential power in assisting clinical diagnosis., (© 2021. The Author(s).)

Background: To date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC)., Methods: In total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients., Results: Among the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC., Conclusions: Cardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pai, Huang, Chen, Fang, Chao, Lo, Li, Wu and Shyr.)

In this study, a novel method with the U-Net-based network architecture, 2D U-Net, is employed to segment the position of lung nodules, which are an early symptom of lung cancer and have a high probability of becoming a carcinoma, especially when a lung nodule is bigger than 15 [Formula: see text]. A serious problem of considering deep learning for all medical images is imbalanced labeling between foreground and background. The lung nodule is the foreground which accounts for a lower percentage in a whole image. The evaluation function adopted in this study is dice coefficient loss, which is usually used in image segmentation tasks. The proposed pre-processing method in this study is to use complementary labeling as the input in U-Net. With this method, the labeling is swapped. The no-nodule position is labeled. And the position of the nodule becomes non-labeled. The result shows that the proposal in this study is efficient in a small quantity of data. This method, complementary labeling could be used in a small data quantity scenario. With the use of ROI segmentation model in the data pre-processing, the results of lung nodule detection can be improved a lot as shown in the experiments.

An effective registration framework between preoperative 3D computed tomography and intraoperative 2D x-ray images is crucial in image-guided therapy. In this paper, a novel 2D/3D hierarchical registration framework via principal-directional Fourier transform operator (HRF-PDFTO) is proposed. First, a PDFTO was established to obtain the in-plane translation and rotation invariance. Then, an initial free template-matching approach based on PDFTO was utilized to avoid initial value assignment and expand the capture range of registration. Finally, the hierarchical registration framework, HRF-PDFTO, was proposed to reduce the dimensions of the registration search space from n 6 to n 2 . The experimental results demonstrated that the proposed HRF-PDFTO has good performance with an accuracy of 0.72 mm, and a single registration time of 16 s, which improves the registration efficiency by ten times. Consequently, the HRF-PDFTO can meet the accuracy and efficiency requirements of 2D/3D registration in related clinical applications.

This article reports our study on a reduced adaptive fuzzy decoupling control for our lower limb exoskeleton system which typically is a multi-input-multi-output (MIMO) uncertain nonlinear system. To show the applicability and generality of the proposed control methods, a more general MIMO uncertain nonlinear system model is considered. By decoupling control, the entire MIMO system is separated into several MISO subsystems. In our experiments, such a system may have problems (even unstable) if a traditional fuzzy approximator is used to estimate the complicated coupling terms. In this article, to overcome this problem, a reduced adaptive fuzzy system together with a compensation term is proposed. Compared to traditional approaches, the proposed fuzzy control approach can reduce possible chattering phenomena and achieve better control performance. By employing the proposed control scheme to an actual 2-DOF lower limb exoskeleton rehabilitation robot system, it can be seen from the experimental results that, as expected, it has good performance to track the model trajectory of a human walking gait. Therefore, it can be concluded that the developed approach is effective for the control of a lower limb exoskeleton system.

This article reports our study on asynchronous H ∞ filtering for fuzzy singular Markovian switching systems with retarded time-varying delays via the Takagi-Sugeno fuzzy control technique. The devised parallel distributed compensation fuzzy filter modes are described by a hidden Markovian model, which runs asynchronously with that of the original fuzzy singular Markovian switching delayed system. The fuzzy asynchronous filtering dealt with in this article contains synchronous and mode-independent filtering as special cases. Novel admissibility and filtering conditions are derived in terms of linear matrix inequalities so as to ensure the stochastic admissibility and the H ∞ performance level. Simulation examples including a single-link robot arm are employed to demonstrate the correctness and effectiveness of the proposed fuzzy asynchronous filtering technique.

To date, few reports have investigated the genetic alterations and clinicopathological features in gastric cancer (GC) according to sex. In total, 2673 GC patients receiving curative surgery were enrolled. Among the 2673 GC patients, 1979 (74.0%) patients were male. After propensity-score matching, 846 patients were enrolled for the analysis, including 423 males and 423 females. There was no significant difference in the clinicopathological features between the sexes. Regarding the initial recurrence pattern, the males were more likely to develop tumor recurrence and liver metastasis than the females, especially in stage III GC. Regarding the molecular analysis, the males had higher PD-L1 expression than the females, especially in stage III GC. In addition, the patients aged ≥ 65 years had higher PD-L1 expression than the patients younger than 65 years. The multivariate analysis demonstrated that sex was among the independent prognostic factors affecting overall survival (OS) and disease-free survival (DFS). Among the patients with liver metastases, PD-L1 expression was more common among the aged male patients. The males were associated with more tumor recurrence and higher PD-L1 expression than the females, especially in stage III GC. For GC patients with liver metastases, PD-L1 testing is recommended, especially among aged male patients.

Purpose: Intermittent hypoxia is a characteristic pathological change in obstructive sleep apnoea (OSA) that can initiate oxidative stress reaction and pro-inflammatory cytokine release. The purpose of this study was to assess the effect and protective mechanism of Astragaloside IV (AS-IV) in intermittent hypoxia-induced human lung epithelial Beas-2B cells., Methods: Human lung epithelial Beas-2B cells were exposed to intermittent hypoxia or normoxia in the absence or presence of AS-IV. MTT assay was performed to determine the cell viability. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malonaldehyde (MDA), and superoxide dismutase (SOD) were measured to evaluate oxidative stress. The levels of cytokines interleukin (IL)-8, IL-1β, and IL-6 were evaluated by enzyme-linked immunosorbent assay and real-time PCR. The expression of Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), and nuclear transcription factor-kappa B (NF-κB) signalling pathways was analysed by western blot., Results: The results showed that AS-IV significantly reduced the levels of ROS, LDH, MDA, IL-8, IL-1β, and IL-6, and increased the level of SOD in intermittent hypoxia-induced Beas-2B cells. It also suppressed the phosphorylation of MAPKs, including P38, c-Jun N-terminal kinase and extracellular signal-regulated kinase, and inhibited the activation of the NF-κB signalling pathway by reducing the phosphorylation of IκBα and p65., Conclusions: AS-IV attenuates inflammation and oxidative stress by inhibiting TLR4-mediated MAPK/NF-κB signalling pathways in intermittent hypoxia-induced Beas-2B cells.

Few reports have investigated different genetic alterations according to age in various cancers. In total, 1749 GC patients receiving curative surgery were enrolled. The clinicopathological features, and prognoses were compared between younger (<65 years) and older (≥65 years) patients. Genetic mutations were analyzed using mass spectrometric single nucleotide polymorphism genotyping technology, including 68 validated mutations within eight genes ( TP53 , ARID1A , BRAF , and the PI3K/AKT pathway) previously reported in relation to age. Younger patients were more likely to be female and have poor cell differentiation, diffuse-type tumors, less lymphovascular invasion, fewer liver metastases, and better 5-year overall survival (OS) (68.0% vs. 54.6%, P <0.001) and disease-free survival (DFS) (65.4% vs. 53.0%, P <0.001) rates than older patients. Regarding the genetic alterations, older patients had more microsatellite instability-high (MSI-H) tumors and more ARID1A mutations than younger patients. Younger patients had significantly better OS and DFS rates than older patients for each pathological Tumor, Node, Metastasis (TNM) stage. Older patients had a significantly higher non-cancer related death rate than younger patients (36.2% vs. 12.3%, P <0.001). Age was an independent prognostic factor in GC. In conclusion, age was associated with different clinicopathological features and genetic alterations in GC with curative surgery.

Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression; immunotherapy and targeted therapy may be beneficial for these patients.