Propofol sedation in routine endoscopy:A case series comparing target controlled infusion vs manually controlled bolus concept

BACKGROUND Many studies have addressed safety and effectiveness of non-anaesthesiologist propofol sedation(NAPS)for gastrointestinal(GI)endoscopy Target controlled infusion(TCI)is claimed to provide an optimal sedation regimen by avoiding under-or oversedation.AIM To assess safety and performance of propofol TCI sedation in comparison with nurse-administered bolus-sedation.METHODS Fouty-five patients undergoing endoscopy under TCI propofol sedation were prospectively included from November 2016 to May 2017 and compared to 87 patients retrospectively included that underwent endoscopy with NAPS.Patients were matched for age and endoscopic procedure.We recorded time of sedation and endoscopy,dosage of medication and adverse events.RESULTS There was a significant reduction in dose per time of propofol administered in the TCI group,compared to the NAPS group(8.2±2.7 mg/min vs 9.3±3.4 mg/min;P=0.046).The time needed to provide adequate sedation levels was slightly but significantly lower in the control group(5.3±2.7 min vs 7.7±3.3 min;P<0.001),nonetheless the total endoscopy time was similar in both groups.No differences between TCI and bolus-sedation was observed for mean total-dosage of propofol rate as well as adverse events.CONCLUSION This study indicates that sedation using TCI for GI endoscopy reduces the dose of propofol necessary per minute of endoscopy.This may translate into less adverse events.However,further and randomized trials need to confirm this trend.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

Propofol Target-Controlled Infusion Modeling in Rabbits:Pharmacokinetic and Pharmacodynamic Analysis

This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.

Target Controllability of Multi-Layer Networks With High-Dimensional Nodes

This paper studies the target controllability of multilayer complex networked systems,in which the nodes are highdimensional linear time invariant(LTI)dynamical systems,and the network topology is directed and weighted.The influence of inter-layer couplings on the target controllability of multi-layer networks is discussed.It is found that even if there exists a layer which is not target controllable,the entire multi-layer network can still be target controllable due to the inter-layer couplings.For the multi-layer networks with general structure,a necessary and sufficient condition for target controllability is given by establishing the relationship between uncontrollable subspace and output matrix.By the derived condition,it can be found that the system may be target controllable even if it is not state controllable.On this basis,two corollaries are derived,which clarify the relationship between target controllability,state controllability and output controllability.For the multi-layer networks where the inter-layer couplings are directed chains and directed stars,sufficient conditions for target controllability of networked systems are given,respectively.These conditions are easier to verify than the classic criterion.

Targeted multi-agent communication algorithm based on state control

As an important mechanism in multi-agent interaction,communication can make agents form complex team relationships rather than constitute a simple set of multiple independent agents.However,the existing communication schemes can bring much timing redundancy and irrelevant messages,which seriously affects their practical application.To solve this problem,this paper proposes a targeted multiagent communication algorithm based on state control(SCTC).The SCTC uses a gating mechanism based on state control to reduce the timing redundancy of communication between agents and determines the interaction relationship between agents and the importance weight of a communication message through a series connection of hard-and self-attention mechanisms,realizing targeted communication message processing.In addition,by minimizing the difference between the fusion message generated from a real communication message of each agent and a fusion message generated from the buffered message,the correctness of the final action choice of the agent is ensured.Our evaluation using a challenging set of Star Craft II benchmarks indicates that the SCTC can significantly improve the learning performance and reduce the communication overhead between agents,thus ensuring better cooperation between agents.

Contact detumbling toward a nutating target through deformable effectors and prescribed performance controller

Detumbling operation toward a rotating target with nutation is meaningful for debris removal but challenging. In this study, a deformable end-effector is first designed based on the requirements for contacting the nutating target. A dual-arm robotic system installed with the deformable end-effectors is modeled and the movement of the end-tips is analyzed. The complex operation of the contact toward a nutating target places strict requirements on control accuracy and controller robustness. Thus, an improvement of the tracking error transformation is proposed and an adaptive sliding mode controller with prescribed performance is designed to guarantee the fast and precise motion of the effector during the contact detumbling.Finally, by employing the proposed effector and the controller,numerical simulations are carried out to verify the effectiveness and efficiency of the contact detumbling toward a nutating target.

Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still controversial.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for Ad-HCC.METHODS From January 2018 to March 2022,217 Ad-HCC patients were retrospectively enrolled.Among them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance bias.Overall survival(OS)was compared using the Kaplan-Meier curve with the log-rank test.The overall objective response rate(ORR)and major complications were also assessed.RESULTS After PSM,82 patients were included both the T-A group and the T-M group.The ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

Observation on the Application Effect of Targeted Infusion Safety Nursing in Inpatients with Cancer

Objective:To study the clinical effect of targeted infusion safety nursing during infusion of inpatients with cancer.Methods:From January 1,2020,to January 1,2023,a total of 6,614 infusion patients were treated in The First Affiliated Hospital of Wenzhou Medical University,and 300 inpatients with cancer were selected as the research objects and randomly divided into the observation group and the control group,with 150 patients in each group.The control group received routine infusion nursing,and the observation group received targeted infusion safety nursing.The targeted infusion safety nursing was judged by comparing the nursing quality assessment,incidence of adverse events,patient compliance,and patients’mastery of infusion knowledge between the two groups.clinical effect.Results:After the targeted infusion safety nursing was given to the patients in the observation group,the patients in this group recognized the nursing quality,and the statistical score was higher than that in the control group;the incidence of adverse events in the observation group was lower than that in the control group.The compliance of the observation group was higher than that of the control group.The mastery of health knowledge in the observation group was also higher than that in the control group and the difference was statistically significant(P<0.02).Conclusion:After implementing targeted infusion safety nursing for inpatients with cancer,it can effectively prevent the occurrence of adverse events,improve patient compliance,and increase the mastery of relevant knowledge of patients.

Two-layer formation-containment fault-tolerant control of fixed-wing UAV swarm for dynamic target tracking

This paper tackles the formation-containment control problem of fixed-wing unmanned aerial vehicle(UAV)swarm with model uncertainties for dynamic target tracking in three-dimensional space in the faulty case of UAVs’actuator and sensor.The fixed-wing UAV swarm under consideration is organized as a“multi-leader-multi-follower”structure,in which only several leaders can obtain the dynamic target information while others only receive the neighbors’information through the communication network.To simultaneously realize the formation,containment,and dynamic target tracking,a two-layer control framework is adopted to decouple the problem into two subproblems:reference trajectory generation and trajectory tracking.In the upper layer,a distributed finite-time estimator(DFTE)is proposed to generate each UAV’s reference trajectory in accordance with the control objective.Subsequently,a distributed composite robust fault-tolerant trajectory tracking controller is developed in the lower layer,where a novel adaptive extended super-twisting(AESTW)algorithm with a finite-time extended state observer(FTESO)is involved in solving the robust trajectory tracking control problem under model uncertainties,actuator,and sensor faults.The proposed controller simultaneously guarantees rapidness and enhances the system’s robustness with fewer chattering effects.Finally,corresponding simulations are carried out to demonstrate the effectiveness and competitiveness of the proposed two-layer fault-tolerant cooperative control scheme.

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

Physical and numerical investigations of target stratum selection for ground hydraulic fracturing of multiple hard roofs

Ground hydraulic fracturing plays a crucial role in controlling the far-field hard roof,making it imperative to identify the most suitable target stratum for effective control.Physical experiments are conducted based on engineering properties to simulate the gradual collapse of the roof during longwall top coal caving(LTCC).A numerical model is established using the material point method(MPM)and the strain-softening damage constitutive model according to the structure of the physical model.Numerical simulations are conducted to analyze the LTCC process under different hard roofs for ground hydraulic fracturing.The results show that ground hydraulic fracturing releases the energy and stress of the target stratum,resulting in a substantial lag in the fracturing of the overburden before collapse occurs in the hydraulic fracturing stratum.Ground hydraulic fracturing of a low hard roof reduces the lag effect of hydraulic fractures,dissipates the energy consumed by the fracture of the hard roof,and reduces the abutment stress.Therefore,it is advisable to prioritize the selection of the lower hard roof as the target stratum.

Nonlocal multi-target controlled controlled gate using Greenberger–Horne–Zeilinger channel and qutrit catalysis

We present a scheme for implementing locally a nonlocal N-target controlled–controlled gate with unit probability of success by harnessing two（N＋1）-qubit Greenberger–Horne–Zeilinger（GHZ） states as quantum channel and N qutrits as catalyser. The quantum network that implements this nonlocal（N＋2）-body gate is built entirely of local single-body and two-body gates, and has only（3N＋2） two-body gates. This result suggests that both the computational depth of quantum network and the quantum resources required to perform this nonlocal gate might be significantly reduced. This scheme can be generalized straightforwardly to implement a nonlocal N-target and M-control qubits gate.

The law of anti-VCAM-1 targeted microbubbles adhesion to activated endothelial cells under controlled shear flow

Microbubbles can enhance the detection in noninvasive ultrasound imaging.Recently,targeted microbubbles have been developed to selectively adhere to specific and overexpressed p molecules in endothelial cells in some pathologic conditions.However,the law of

Study of targeted and controlled release of 5-fluorouracil-loaded PLA nanoparticles and microspheres on treatment of gastric tumor

The aim of this paper was to evaluate controlled release behavior and the therapeutic efficacy of 5-FU-loaded Poly(lactic acid) (PLA)microspheres to human gastric cancer xenograft, and the targeting effect of VEGF/5-FU loaded PLA nanoparticles. 5-FU-loaded PLA microspheres were prepared by an emulsion evaporation method, and were characterized by scanning electron microscopy (SEM). 5-FU loaded PLA nanoparticles were characterized by (TEM), and particle size analyzer determined the distribution of nanoparticles size. The release performances of 5-FU microspheres in vitro were studied in PH 7.4 phosphate buffered saline. The therapeutic efficacy of 5-FU-loaded PLA microspheres in vivo were studied using MGC-803 (human stomach cancer) xenograft. 32 nude mice were divided into four groups (n =8), 5-FU loaded PLA microspheres were injected at tumor site. VEGF121 monoclonal antibody was connected with 5-FU loaded PLA nanoparticles through carbodimide. The targeted effect of VEGF 5-FU loaded nanoparticles in vivo were observed by single photon emission computed tomography (SPECT) after tail vein injection at 1 h and 2 h. SEM observation showed that microspheres were spherical, and the diameters of two kinds of microspheres were 1 μm and 5 μm respectively. The mean diameter of nanoparticles was 191.0 nm, and the index of polydispersity was 0.202. The drug was released following biphasic kinetics, initial burst and the following steady phase. 1 μm and 5 μm 5-FU-loaded microspheres both resulted in increased life span (1 μm microspheres median survival time=40.63 days, 5 μm microspheres median survival time=62.25 days), against 5-FU pure drug (median survival time=14.5 days). These results strongly suggest that 5-FU-loaded PLA microspheres increase life span of nude mice bearing MGC-803 tumors. After injection for 2 h, almost all the VEGF/5-FU loaded PLA nanoparticles could centralize at the human gastric cancer xenograft sites. That demonstrated VEGF monoclonal antibody remain its bioactivity after connection with nanoparticles, VEGF/5-FU loaded PLA nanoparticles had very exact targeting function for gastric tumor xenograft.

Integrated Guidance and Control of Homing Missiles Against Ground Fixed Targets

This paper presents a scheme of integrated guidance and autopilot design for homing missiles against ground fixed targets. An integrated guidance and control model in the pitch plane is formulated and further changed into a normal form by nonlinear coordinate transformation. By adopting the sliding mode control approach, an adaptive nonlinear control law of the system is designed so that the missile can hit the target accurately with a desired impact attitude angle. The stability analysis of the closed-loop system is also conducted. The numerical simulation has confirmed the usefulness of the proposed design scheme.

Target Seeker Gyro and Controls

A composite target seeker gyro with dual spectral range infrared rays and millimeter waves, and the associated control methodology are developed. The static pressure air floated ball bearing is used to sustain the outer frame, the optical fiber and wave guide are used to transmit these two kinds of signals to the rear part of the gyro, and the stator coils are used to get non contact angular measurement. Composite guiding, scanning, tracing and controlling can be achieved, the maximum tracing angular velocity can be as high as 16(°)/s.

Target Vehicle Selection Algorithm for Adaptive Cruise Control Based on Lane-changing Intention of Preceding Vehicle

To improve the ride comfort and safety of a traditional adaptive cruise control(ACC)system when the preceding vehicle changes lanes,it proposes a target vehicle selection algorithm based on the prediction of the lane-changing intention for the preceding vehicle.First,the Next Generation Simulation dataset is used to train a lane-changing intention prediction algorithm based on a sliding window support vector machine,and the lane-changing intention of the preceding vehicle in the current lane is identified by lateral position offset.Second,according to the lane-changing intention and collision threat of the preceding vehicle,the target vehicle selection algorithm is studied under three different conditions:safe lane-changing,dangerous lane-changing,and lane-changing cancellation.Finally,the effectiveness of the proposed algorithm is verified in a co-simulation platform.The simulation results show that the target vehicle selection algorithm can ensure the smooth transfer of the target vehicle and effectively reduce the longitudinal acceleration fluctuation of the subject vehicle when the preceding vehicle changes lanes safely or cancels their lane change maneuver.In the case of a dangerous lane change,the target vehicle selection algorithm proposed in this paper can respond more rapidly to a dangerous lane change than the target vehicle selection method of the traditional ACC system;thus,it can effectively avoid collisions and improve the safety of the subject vehicle.

Impedance control of multi-arm space robot for the capture of non-cooperative targets

Robotic systems are expected to play an increasingly important role in future space activities. The robotic on-orbital service, whose key is the capturing technology, becomes a research hot spot in recent years. This paper studies the dynamics modeling and impedance control of a multi-arm free-flying space robotic system capturing a non-cooperative target. Firstly, a control-oriented dynamics model is essential in control algorithm design and code realization. Unlike a numerical algorithm, an analytical approach is suggested. Using a general and a quasi-coordinate Lagrangian formulation, the kinematics and dynamics equations are derived.Then, an impedance control algorithm is developed which allows coordinated control of the multiple manipulators to capture a target.Through enforcing a reference impedance, end-effectors behave like a mass-damper-spring system fixed in inertial space in reaction to any contact force between the capture hands and the target. Meanwhile, the position and the attitude of the base are maintained stably by using gas jet thrusters to work against the manipulators' reaction. Finally, a simulation by using a space robot with two manipulators and a free-floating non-cooperative target is illustrated to verify the effectiveness of the proposed method.