Impact of the diagnosis of metabolic dysfunction-associated fatty liver disease and non-alcoholic fatty liver disease in patients undergoing liver transplantation for hepatocellular carcinoma.

Purpose: Whether the diagnosis of non-alcoholic fatty liver disease or metabolic dysfunction-associated fatty disease has a different impact on liver transplant recipients with hepatocellular carcinoma is not yet clear. Methods: Data from a two-center retrospective cohort study were collected to compare and investigate the differences between non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease in clinicopathologic parameters and prognosis among liver transplant recipients with hepatocellular carcinoma. Results: A total of 268 liver transplant recipients with hepatocellular carcinoma were included. The prevalence among pre- and post-transplant metabolic dysfunction-associated fatty liver disease was 10.82% and 30.22%, while for non-alcoholic fatty liver disease, it was 7.09% and 26.87%, respectively. The clinicopathological parameters were similar between the two pre-transplant groups. In contrast, the post-transplant group with metabolic dysfunction-associated fatty liver disease exhibited a higher prevalence of diabetes mellitus and a greater body mass index. However, the other parameters were similar between the two post-transplant groups (p > 0.05). Factors such as the largest tumor size > 4 cm, microvascular invasion, lack of tumor capsule, post-transplant metabolic dysfunction-associated fatty liver disease, and decreased post-transplant lymphocyte percentage were related to an increased risk of recurrence. Conclusion: In patients undergone liver transplantation for hepatocellular carcinoma, the diagnosis of metabolic dysfunction-associated fatty disease is more strongly associated with metabolic abnormalities than the diagnosis of non-alcoholic fatty liver disease and is an independent predictor of hepatocellular carcinoma recurrence.

Finite-Time Time-Varying Formation Tracking for Heterogeneous Nonlinear Multiagent Systems Using Adaptive Output Regulation.

The finite-time output time-varying formation tracking (TVFT) problem for heterogeneous nonlinear multiagent system (MAS) is investigated in this article, where the dynamics of the agents can be nonidentical, and leader's input is unknown. The target of this article is that the outputs of followers need to track leader's output and realize the desired formation in finite time. First, for removing the assumption that all agents are required to know the information of leader's system matrices and the upper boundary of its unknown control input in previous studies, a kind of finite-time observer is constructed by exploiting the neighboring information, which can estimate not only the leader's state and system matrices but also can compensate for the effects of unknown input. On the basis of the developed finite-time observers and adaptive output regulation method, a novel finite-time distributed output TVFT controller is proposed with the help of the technique of coordinate transformation by introducing an extra variable, which removes the assumption that the generalized inverse matrix of follows' input matrix needs to be found in the existing results. By means of the Lyapunov and finite-time stability theory, it is proven that the expected finite-time output TVFT can be realized by the considered heterogeneous nonlinear MASs within a finite time. Finally, simulation results demonstrate the efficacy of the proposed approach.

Time-varying formation tracking for multi-agent systems with maneuvering leader under DDoS attacks and actuator faults.

Time-varying formation tracking problems for multi-agent systems (MASs) under distributed Denial-of-Service (DDoS) attacks and actuator faults are studied. To deal with the hybrid threats at the cyber and physical layers, an estimator-based fault-tolerant hierarchical control scheme is introduced, which is applicable to channel-wise asynchronous communication. Sufficient conditions for formation tracking of maneuvering leader with ultimately bounded error are obtained, and the particular case of periodic communication and attacks with constrained duration and frequency is further analyzed. Comparative physical simulations based on ROS and Gazebo are first conducted to show the resilience of our scheme against the threats. Finally, an experimental platform containing DJI Tello quadrotors and a self-developed ground control station is built, based on which practical experiments with four quadrotors are carried out to evaluate the effectiveness and engineering practicability of the proposed control framework.

Impact of metabolic dysfunction-associated fatty liver disease on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease was proposed by international consensus to redefine the metabolic abnormal condition. However, its impact on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma has not been explored. METHODS: A two-center retrospective cohort study on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma was performed to analyze the impact of metabolic dysfunction-associated fatty liver disease on the clinicopathologic parameters and prognosis. RESULTS: There were 201 liver transplant recipients enrolled from two hospitals in our study. The pre- and post-transplant prevalences of metabolic dysfunction-associated fatty liver disease were 9.95% and 28.86%, respectively. The clinicopathological parameters revealed a similarity between patients with and without pre-transplant metabolic dysfunction-associated fatty liver disease. In contrast, the group with post-transplant metabolic dysfunction-associated fatty liver disease was linked with older age, a higher hepatitis recurrence rate and incidence of cardiovascular disease, usage of calcineurin inhibitors, a greater body mass index and waist circumference, lower albumin and high-density lipoprotein cholesterol levels, and poorer tumor-free survival and overall survival. The multivariate analysis showed the largest tumor size >4 cm (95% confidence intervals: 0.06~0.63, p = 0.006), microvascular invasion (95% confidence intervals: 1.61~14.92, p = 0.005), post-transplant metabolic dysfunction-associated fatty liver disease (95% confidence intervals: 1.40~10.60, p = 0.009), and calcineurin inhibitors-based regimen (95% confidence intervals: 0.33~0.96, p = 0.036) were the independent risk factors for recurrent hepatocellular carcinoma. CONCLUSIONS: Our study suggests that post-transplant metabolic dysfunction-associated fatty liver disease is more closely to metabolic abnormalities and that it can help identify liver transplant recipients at high risk of recurrent hepatocellular carcinoma.

IL-10 dependent modulatory effect of regulatory B10 cells on local scar formation following Roux-en-Y choledochojejunostomy in a novel rat model.

Choledochojejunostomy has been common surgical treatment of biliary tract disease. Scar formation at anastomotic often results in postoperative complications associated with bleak post-operative recovery, in which local inflammation may be a potential target to modulate local scar formation. This study investigated the effect of regulatory B10 cells on local scar formation through interleukin-10 signal pathway following Roux-en-Y choledochojejunostomy (RCJS) in a novel rat model. Sprague-Dawley (SD) rats with RCJS were randomly divided into blank group, experimental group, IL-10 blocking group, control group, and received different interventions and duration. Injected through dorsal vein of penis, rats in different groups were treated respectively according to scheme. These interventions were performed during surgery, on 1st day, and 2nd day after surgery. Related indexes, including blood examination, specimen tissue of anastomotic detection, were recorded and compared in different interventional groups. Rats in experimental groups had more rapid recovery in liver function and inflammatory index, and higher in IL-10 level. Flow cytometry analysis showed that rats in experimental groups had highest content of B10 cells and lowest content of CD4+CD25- T cells in peripheral blood. Wider anastomotic by macroscopical observation, and slighter proliferation of collagen fiber and smooth muscle fiber, lower α-SMA and TGF-ß1 levels by pathological staining were detected in experimental groups. Higher expression of the IL-10 gene and lower expression of TGF-ß1 at anastomotic were detected in experimental groups. B10 cells may relieve local inflammation of anastomotic following RCJS in rats through IL-10-dependent modulatory effect, and improve local scar formation.

Protective Effects of Different Hypothermal Preservation Solutions on Structure and Function of Isolated Rat Arteries.

OBJECTIVE: With the increasing application of vascular reconstruction in surgical procedures, allogeneic vessels are becoming more popular in clinical practice due to their abundant sources, precise diameter matching, improved histocompatibility, and higher long-term patency rate. This study aimed to investigate the protective effect of various preservation solutions on the function and structure of the isolated rat abdominal aorta preserved under hypothermal conditions. METHODS: The study utilized a total of 150 Sprague-Dawley (SD) rats, with 144 rats allocated to the experimental groups and 6 rats allocated to the control groups. The abdominal aorta of the rats was chosen as the subject of our research. The aorta in the experimental groups were randomly assigned to 4 groups: University of Wisconsin (UW) solution group, histidine-tryptophan-ketoglutarate (HTK) solution group, normal saline (NS) group, and sodium lactate Ringer's solution (RS) group. Samples were subjected to examination after preservation periods of 1 day, 3 days, 5 days, 7 days, 14 days, 30 days, and 90 days. Evaluation of vascular physiological function involved detecting and assessing vasoconstriction ability and measuring cell viability through the MTT test. Evaluation of the vascular wall structure involved tension tolerance tests and pathological staining. RESULTS: The pathogen-positive rate in the HTK group and NS group at 1 month was 16.7%. Regarding the vascular skeleton structure, both the UW group and HTK group exhibited intact structures after 2 weeks of preservation, with slightly edematous collagen and elastic fibers, which was significantly better than that of the NS group and RS group. In terms of cell activity and contractile function, all preservation groups showed similar effects within 2 weeks. However, after 2 weeks, the UW group showed the most favorable preservation effect (P<0.05). In terms of vascular tension, different groups exhibited similar effects within 1 week. However, after 2 weeks, the UW group showed the best preservation effect (P<0.05). CONCLUSION: All 4 types of preservation solution had a preservation effect on the structure and function of isolated blood vessels during short-term hypothermal preservation. However, after 2-week preservation, the UW solution was found to be the most suitable solution for the preservation of blood vessels.

The coagulation-related genes for prognosis and tumor microenvironment in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by challenging early diagnosis and poor prognosis. It is believed that coagulation has an impact on the tumor microenvironment of PDAC. The aim of this study is to further distinguish coagulation-related genes and investigate immune infiltration in PDAC. METHODS: We gathered two subtypes of coagulation-related genes from the KEGG database, and acquired transcriptome sequencing data and clinical information on PDAC from The Cancer Genome Atlas (TCGA) database. Using an unsupervised clustering method, we categorized patients into distinct clusters. We investigated the mutation frequency to explore genomic features and performed enrichment analysis, utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) to explore pathways. CIBERSORT was used to analyze the relationship between tumor immune infiltration and the two clusters. A prognostic model was created for risk stratification, and a nomogram was established to assist in determining the risk score. The response to immunotherapy was assessed using the IMvigor210 cohort. Finally, PDAC patients were recruited, and experimental samples were collected to validate the infiltration of neutrophils using immunohistochemistry. In addition, and identify the ITGA2 expression and function were identified by analyzing single cell sequencing data. RESULTS: Two coagulation-related clusters were established based on the coagulation pathways present in PDAC patients. Functional enrichment analysis revealed different pathways in the two clusters. Approximately 49.4% of PDAC patients experienced DNA mutation in coagulation-related genes. Patients in the two clusters displayed significant differences in terms of immune cell infiltration, immune checkpoint, tumor microenvironment and TMB. We developed a 4-gene prognostic stratified model through LASSO analysis. Based on the risk score, the nomogram can accurately predict the prognosis in PDAC patients. We identified ITGA2 as a hub gene, which linked to poor overall survival (OS) and short disease-free survival (DFS). Single-cell sequencing analysis demonstrated that ITGA2 was expressed by ductal cells in PDAC. CONCLUSIONS: Our study demonstrated the correlation between coagulation-related genes and the tumor immune microenvironment. The stratified model can predict the prognosis and calculate the benefits of drug therapy, thus providing the recommendations for clinical personalized treatment.

Effects of different preservation schemes on isolated rat artery.

Allogeneic blood vessels are regarded as one of the best natural substitutes for diseased blood vessels due to their good vascular compliance and histocompatibility. Since the supply and demand of allograft blood vessels do not always match in time and space, a good preservation scheme for isolated blood vessels is essential. The abdominal aortas of 110 male Sprague-Dawley (SD) rats were randomly divided into three groups, including cold storage group (4°C) (CSG), frozen storage group (FSG) and ambient storage group (25 ± 2°C) (ASG). Seven time points of preservation for 1, 3, 5, 7, 14, 30 and 90 days were set for detection. The changes in vascular physiological function were evaluated by MTT test and vasoconstriction ability detection, and the changes in vascular wall structure were evaluated by the tension tolerance test and pathological staining. The vascular function of CSG was better than FSG within first the 7 days, but the result was opposite since the 14th day. The vascular wall structure, collagen and elastic fibres of vessels, in CSG, showed oedema within 30 days, and continuous disintegration and rupture at 90 days. The vessel wall structure of FSG remained intact within 90 days. The tensile strength of the vessels in CSG was better than that in FSG within 5 days, and there was no statistical difference between the two groups between the 7th and 30th day, and then, the FSG was higher than CSG on the 90th day. Both cold storage and frozen storage could be applied as safe and effective preservation schemes for isolated rat artery within first 30 days. Cold storage is recommended when the storage time is <14 days, and then, frozen storage is better.

Measurement based dimension descent association algorithm for OTHR multi-detection multi-target tracking.

The problem of multi-detection multi-target tracking (MDMTT) using over-the-horizon radar in dense clutter environment is studied in this paper. The biggest challenge of MDMTT is the 3-dimensional multipath data association among measurements, detection models and targets. In particular, a lot of clutter measurements are generated in dense clutter environment, which increase the computational burden of 3-dimensional multipath data association greatly. A measurement based dimension descent association (DDA) algorithm is proposed to solve the 3-dimensional multipath data association, which decomposes the 3-dimensional multipath data association into two 2-dimensional data associations. The proposed algorithm can reduce the computational burden compared with the optimal 3-dimensional multipath data association and the computational complexity is analyzed. Besides, a time extension method is designed to detect the new-born targets that appear in the tracking scene, which is based on the sequential measurements. The convergence of the proposed measurement based DDA algorithm is analyzed. The estimation error can convergence to 0 as the number of Gaussian mixtures tends to infinity. The effectiveness and rapidity of the measurement based DDA algorithm are demonstrated by the comparative simulation with the previously proposed algorithms.

Distributed output formation tracking control of heterogeneous multi-agent systems using reinforcement learning.

This paper studies the distributed time-varying output formation tracking problem for heterogeneous multi-agent systems with both diverse dimensions and parameters. The output of each follower is supposed to track that of the virtual leader while accomplishing a time-varying formation configuration. First, a distributed trajectory generator is proposed based on neighboring interactions to reconstitute the state of virtual leader and provide expected trajectories with the formation incorporated. Second, an optimal tracking controller is designed by the model-free reinforcement learning technique using online off-policy data instead of requiring any knowledge of the followers' dynamics. Stabilities of the learning process and resulting controller are analyzed while solutions to the output regulator equations are equivalently obtained. Third, a compensational input is designed for each follower based on previous learning results and a derived feasibility condition. It is proved that the output formation tracking error converges to zero asymptotically with the biases to cost functions being restricted arbitrarily small. Finally, numerical simulations verify the proposed learning and control scheme.

Distributed Fault-Tolerant Formation Tracking Control for Multiagent Systems With Multiple Leaders and Constrained Actuators.

The distributed formation tracking control problem with multiple leaders under actuator faults and constraints is investigated in this article. All followers in the multiagent system should achieve a desired time-varying formation and track the convex combination of multiple leaders. To accomplish the control task, an active reconfigurable control scheme is proposed using the local information between agents, as well as the fault values of individuals provided by fault estimation observers. Combining with the Lyapunov stability theorem and the property of the Laplacian matrix, the control gains are calculated using the adaptive technique with a formation tracking feasibility condition. The original reconfigurable protocol is modified by utilizing anti-windup compensators to against saturation phenomenons (both magnitude and rate) in actuators. The simulation results validate that the presented scheme can address the faults as well as the actuator saturation.

Practical Output Containment of Heterogeneous Nonlinear Multiagent Systems Under External Disturbances.

The practical output containment problem for heterogeneous nonlinear multiagent systems under external disturbances generated by an exosystem is investigated in this article. It is required that the outputs of followers converge to the predefined convex combination of leaders' outputs. One of the major challenges in solving such a problem lies in dealing with the coupling among different nonlinearities, state dimensions, and system matrices of heterogeneous agents. To overcome the aforementioned challenge, a distributed observer-based control protocol is developed and employed. First, an adaptive state observer for estimating the states of all the leaders is constructed based on the neighboring interactions. Second, two new classes of observers are constructed for each follower exploiting the output information of the follower, in which the adaptive neural networks (NNs)-based approximation is exploited to compensate for the unknown nonlinearity in the followers' dynamics. A practical output containment control protocol is then generated by the proposed observers, where the control parameters are determined by an algorithm including two steps. Furthermore, with the help of the Lyapunov stability theory and the output regulation method, the practical output containment criteria for the considered closed-loop system under the influences of external disturbances are derived on the basis of the presented control protocol. Finally, the derived theoretical results are illustrated by a simulation example.

Effects of different preservation methods of human iliac veins.

With the progress of vascular anastomosis technology, the radical resection surgery of cancer combining with vascular resection and reconstruction has been focused by surgeon. As a natural substitute material for blood vessel, vascular allografts have good vascular compliance and histocompatibility. Generally, the donated veins could not be used immediately, and need to be well preserved. So, it is greatly significant to do research in the preservation effects of different preservation methods on veins. In this study, the effects of different preservative methods of human iliac veins were compared and analyzed in terms of cell viability, vascular wall structure and tension resistance. The donated human iliac veins were randomly divided into three groups: Cold Storage Group (4 °C) (CSG), Frozen Storage Group (-186 °C) (FSG)and Fresh Control Group (FCG). Six detection time-points of preservation for 1, 3, 5, 7, 14, 28 days were set respectively. There are ten samples in each group and each time-point separately. Survival and apoptosis of vascular cell were evaluated by MTT assay and Tunel fluorescence staining. Tensile test was used to evaluate mechanical properties of vessels. The changes of vascular endothelial cells, smooth muscle cells, collagen fibers and elastic fibers were evaluated by HE staining, Masson staining and EVG staining. Furthermore, the changes of organelles were observed by transmission electron microscope. With the extension of preservation period, the vascular cell viability and tension resistance of two groups decreased, and the apoptotic cells increased gradually. The apoptosis index of CSG was higher than FSG at each time point (P < 0.05). In terms of cell viability, CSG was higher within 3 days (P < 0.05), both groups were same between 3 and 14 days, and then CSG lower than FSG after 14 days (P < 0.05). In terms of tension resistance, CSG was stronger than FSG (P < 0.05) in first 7 days, both groups were same in 2nd week, and then CSG was weaker in 4th week (P < 0.05). In terms of vascular wall structure, in CSG, vascular endothelial cells were damaged and shed, smooth muscle cells were edema after 14 days, but the cell membrane and intercellular connection were still intact. In 4th week, endothelial cells were completely damaged and shed, the boundary of smooth muscle cell membrane was unclear, intercellular connection was damaged. Moreover, organelles were destroyed and disappeared, perinuclear condensation of chromatin was observed, and some cells had incomplete nuclear membrane or nuclear fragmentation; However, there were no obvious changes in the FSG within 28 days. Finally, local exfoliation and destruction of endothelial cells and edema-like changes of organelles were observed; the collagen fibers and elastic fibers of blood vessels in the two groups had no obvious damage and change within 28 days. For excised human iliac vein, cold and frozen storage can effectively preserve the cell viability, wall structure and tension resistance of blood vessels. With the extension of preservation time, the related performance of vessels declined in varying degrees. Within first week, the effect of cold storage is better than frozen storage, but frozen storage is significantly better than cold storage after 2 weeks.

Privacy-preserving push-sum distributed cubature information filter for nonlinear target tracking with switching directed topologies.

To address the data security issue of distributed state estimation, this paper proposes a novel consensus-based cubature information filtering algorithm for sensitive nonlinear target tracking under restricted communication. Through a privacy-preserving approach via state decomposition, the algorithm can protect the privacy of local information from adversaries without sacrificing global estimation accuracy. Based on the push-sum consensus, the distributed approach is further extended to switching directed topologies, which is more feasible for tracking with communication constraints. Our method's average convergence, privacy preservation, and stability are theoretically proved. Finally, simulations are conducted to evaluate the algorithm's performance on security, accuracy, and robustness.

Research progress of improving demyelination in treatment of spinal cord injury / 中国药理学通报

Axonal demyelination is an important factor causing neurological dysfunction after spinal cord injury. Retaining the integrity of myelin sheath and promoting remyelination play an important role in the functional recovery of spinal cord injury. The bottleneck of the failure of remyelination is the inability of myelin-forming cells (oligodendrocytes and Schwann cells) to differentiate and mature. In recent years related research on spinal cord injury demyelination has found that cell transplantation, neuregulin-1 and hydrogel can effectively enhance remyelination, and identified aquaporin-4 (aquaporin-4, AQP4), metal-loproteinase (Matrix metailoproteinase, MMP) may be a potential therapeutic target to promote myelin recovery after spinal cord injury. This review discusses the research progress of enhancing remyelination after spinal cord injury, providing ideas for the further development of new methods for the treatment of spinal cord injury.

Transanal drainage tube for prevention of anastomotic leak after anterior resection for rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To assess the effectiveness of transanal drainage tube (TDT) in reducing the incidence of anastomotic leak following anterior resection in patients with rectal cancer. Methods: We conducted a systematic search for relevant studies published from inception to October 2022 across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. Meta-analysis was performed using Review Manager 5.4 software. The primary outcomes included total incidence of anastomotic leak, grade B and C anastomotic leak rates, reoperation rate, anastomotic bleeding rate, and overall complication rate. Results: Three randomized controlled trials involving 1115 patients (559 patients in the TDT group and 556 in the non-TDT group) were included. Meta-analysis showed that the total incidences of anastomotic leak and of grade B anastomotic leak were 5.5% (31/559) and 4.5% (25/559), respectively, in the TDT group and 7.9% (44/556) and 3.8% (21/556), respectively, in the non-TDT group. These differences are not statistically significant (P=0.120, P=0.560, respectively). Compared with the non-TDT group, the TDT group had a lower incidence of grade C anastomotic leak (1.6% [7/559] vs. 4.5% [25/556]) and reoperation rate (0.9% [5/559] vs. 4.3% [24/556]), but a higher incidence of anastomotic bleeding (8.2% [23/279] vs. 3.6% [10/276]). These differences were statistically significant (P=0.003, P=0.001, P=0.030, respectively). The overall complication rate was 26.5%(74/279) in the TDT group and 27.2% (75/276) in the non-TDT group. These differences are not statistically significant (P=0.860). Conclusions: TDT did not significantly reduce the total incidence of anastomotic leak but may have potential clinical benefits in preventing grade C anastomotic leak. Notably, placement of TDT may increase the anastomotic bleeding rate.

Research progress of functional alignment robot assisted knee replacement / 中国骨伤

The correct alignment of the knee joint is considered to be one of the most influential factors in determining the long-term prognosis after total knee arthroplasty(TKA). In order to achieve the correct alignment goal, many different alignment concepts and surgical techniques have been established. For example, mechanical alignment(MA), kinematic alignment(KA) and functional alignment(FA) have their own characteristics. MA focuses on achieving neutral alignment of the limbs, parallel and equal bone gaps during stretching and flexion. KA aims to restore the patient 's natural joint line, make the joint level and angle normal and improve the physiological soft tissue balance, and strive to reproduce the normal knee function;among them, functional alignment(FA) developed with robot-assisted surgery technology is a relatively new alignment concept. It not only considers the alignment of the body, but also aims to achieve flexion and extension balance, while respecting the native soft tissue capsule. It not only restores the plane and slope of the in situ joint line accurately during the operation, but also takes into account the balance of soft tissue, which is a better alignment method. Therefore, it is of great significance to correctly construct the lower limb force line of patients, which is helpful to restore knee joint function, relieve pain symptoms and prolong the service life of prosthesi. However, compared with traditional TKA, the operation time of robot-assisted FA-TKA is prolonged, which means that the probability of postoperative infection will be greater. At present, most studies of FA technology report short-term results, and the long-term efficacy of patients is not clear. Therefore, long-term research results are needed to support the application of this technology. Therefore, the author makes a review on the research status of functional alignment.

Neuroadaptive Output Formation Tracking for Heterogeneous Nonlinear Multiagent Systems With Multiple Nonidentical Leaders.

This article investigates the practical time-varying output formation tracking (TVOFT) problem for heterogeneous nonlinear multiagent systems (MASs) having multiple leaders, where agents herein could have heterogeneous dynamics and interact with each other under event-triggered communications. It is required that the outputs of followers not only track the predefined convex combination of multiple leaders but also achieve the desired time-varying formation simultaneously. The existing works on formation tracking problems for MASs with multiple leaders depend on the assumption that each follower is a well-informed or uninformed follower, where the well-informed follower is required to have all the leaders as its neighbor. To remove the limitation, a fully distributed observer-based formation tracking control protocol is developed and employed. First, an adaptive state observer with an edge-based event-triggered mechanism for estimating the states of multiple leaders is proposed based on the neighboring interactions, which eliminates the unexpected Zeno behavior. Second, a novel observer is constructed for each follower by exploiting the output information of the follower, in which the adaptive neural network (NN)-based approximation is exploited to compensate for the unknown nonlinearity. A practical TVOFT control protocol is then generated by the proposed observers, where the parameters are determined by an algorithm including five steps. With the help of Lyapunov stability theory and output regulation method, a practical TVOFT criterion for the considered closed-loop system is derived. Finally, the effectiveness of the proposed control scheme is illustrated by a numerical example.