Experimental models of high-risk bowel anastomosis in rats:A systematic review

BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Hepatitis C Virus Experimental Model Systems and Antiviral drug Research

An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.

MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

Advances in viral encephalitis:Viral transmission,host immunity,and experimental animal models

Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.

Factors Controlling Deoxygenation of "Floodwater" Overlying an Acid Sulfate Soil: Experimental Modeling

An incubation experiment was conducted to simulate the effect of flooding onwater deoxygenation in acid sulfate soil floodplain systems. The originally oxygenated 'floodwater'could be deoxygenated immediately following 'flooding' and it is likelythat this was caused mainlyby decomposition of organic debris from the inundated plants. Deoxygenation eventually led to thedepletion of dissolved oxygen (DO) in the 'floodwater' and it is highly possible that this resultedin the transformations of ferric Fe to ferrous Fe, sulfate to hydrogen sulfide. and organic nitrogento ammonia (ammonification). The accumulation of these reduced substances allows the 'floodwater'to develop DO-consuming capacity (DOCC). When the 'floodwater' is mixed with the introducedoxygenated water, apart from the dilution effects, the reduced substances contained in the'floodwater' oxidize to further consume DO carried by the introduced water. However, it appears thatthe DO drop in the mixed water can only last for a few hours if no additional DO-depleted'floodwater' is added. Entry of atmospheric oxygen into the water can raise the DO level of themixed water arid lower water pH through the oxidation of the reduced substances.

EXPERIMENTAL MODELING OF MIDDLE-RISE BUILDING VIA AMBIENT MODAL IDENTIFICATION

Experimental modeling of a middle-rise office building via ambient modal identification is presented. A 200-DOF (Dimension of freedom) test model is designed to correlate with finite element mode. A newly developed frequency-spatial domain decomposition ( FSDD ) technique is used to identify modal characteristics of the full-size building by using ambient response measurements. In the interested frequency ranges of 0～4.5 Hz and 0～ 6.5 Hz altogether 9 bending and torsion modes are identified. As one of the major focuses of the project, the accurate damping estimation is conducted based on FSDD. The identified modal frequencies and mode shapes are utilized for finite element model tuning. Excellent agreement has been achieved with respect to the final tuned finite element (FE) model up to 9 modes.

FLOW STRESS MODELING FOR AERONAUTICAL ALUMINUM ALLOY 7050-T7451 IN HIGH-SPEED CUTTING

The high temperature split Hopkinson pressure bar （SHPB） compression experiment is conducted to obtain the data relationship among strain, strain rate and flow stress from room temperature to 550 C for aeronautical aluminum alloy 7050-T7451. Combined high-speed orthogonal cutting experiments with the cutting process simulations, the data relationship of high temperature, high strain rate and large strain in high-speed cutting is modified. The Johnson-Cook empirical model considering the effects of strain hardening, strain rate hardening and thermal softening is selected to describe the data relationship in high-speed cutting, and the material constants of flow stress constitutive model for aluminum alloy 7050-T7451 are determined. Finally, the constitutive model of aluminum alloy 7050-T7451 is established through experiment and simulation verification in high-speed cutting. The model is proved to be reasonable by matching the measured values of the cutting force with the estimated results from FEM simulations.

Experimental verification of mathematical model for multiphase flow in air-agitated seed precipitation tank

In order to check the validity of the mathematical model for analyzing the flow field in the air-agitated seed precipitation tank,a scaled down experimental apparatus was designed and the colored tracer and KCl tracer were added in the apparatus to follow the real flow line.Virtue tracers were considered in the mathematical model and the algorithm of tracers was built.The comparison of the results between the experiment and numerical calculation shows that the time of the tracer flows out of stirring tube are 40 s in the experiment and 42 s in numerical calculated result.The transient diffusion process and the solution residence time of the numerical calculation are in good agreement with the experimental results,which indicates that the mathematical model is reliable and can be used to predict the flow field of the air-agitated seed precipitation tank.

The influence of inter-band rock on rib spalling in longwall panel with large mining height

In order to improve rib stability,failure criteria and instability mode of a thick coal seam with inter-band rock layer are analysed in this study.A three-dimensional mechanical model is established for the rib by considering the rock layer.A safety factor is defined foy the rib,and it is observed that the safety factor exhibits a positive correlation with the thickness and strength of the inter-band rock.A calculation method for determining critical parameters of the rock layer is presented to ensure the rib stability.It is revealed that incomplete propagation of the fracture at the hard rock constitutes a fundamental prerequisite for ensuring the rib stability.The influence of the position of the inter-band rock in the coal seam on failure mechanism of the rib was thoroughly investigated by developing a series of physical models for the rib at the face area.The best position for the inter-band rock in the coal seam is at a height of 1.5 m away from the roof line,which tends to provide a good stability state for the rib.For different inter-band rock positions,two ways of controlling rib by increasing supports stiffness and flexible grouting reinforcement are proposed.

Calculating the number of radial cracks around a wellbore fractured by liquid CO2 phase transition blasting technology

Integrating liquid CO_(2)phase transition blasting(LCPTB)technology with hydraulic fracturing(HF)methods can help reduce wellbore damage,create multiple radial fractures,and establish a complex fracture network.This approach significantly increases the recovery efficiency of low-permeability oil and gas fields.Accurately calculating the number of fractures caused by LCPTB is necessary to predict production enhancement effects and optimize subsequent HF designs.However,few studies are reported on large-scale physical model experiments in terms of a method for calculating the fracture number.This study analyzed the initiation and propagation of cracks under LCPTB,derived a calculation formula for crack propagation radius under stress waves,and then proposed a new,fast,and accurate method for calculating the fracture number using the principle of mass conservation.Through ten rock-breaking tests using LCPTB,the study confirmed the effectiveness of the proposed calculation approach and elucidated the variation rule of explosion pressure,rock-breaking scenario,and the impact of varying parameters on fracture number.The results show that the new calculation method is suitable for fracturing technologies with high pressure rates.Recommendations include enlarging the diameter of the fracturing tube and increasing the liquid CO2 mass in the tube to enhance fracture effectiveness.Moreover,the method can be applied to other fracturing technologies,such as explosive fracturing(EF)within HF formations,indicating its broader applicability and potential impact on optimizing unconventional resource extraction technologies.

Advances in cytokine-mediated mechanisms for cardiac regeneration and repair post-myocardial infarction:a comprehensive review

Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studies have shown that cytokines participate in cardiac regeneration and repair by modulating cellular proliferation,differentiation,and apoptosis post-MI.Here,we explored the crucial role of cytokines in cardiac regeneration and repair processes in experimental animal models,detailing how cytokines modulate cellular mechanisms involved in repairing cardiac tissue post myocardial infarction(MI).Specifically,it highlights the activation of cardiac stem cells and progenitors,the regulation of inflammatory responses to prevent excessive damage,and the involvement in matrix remodeling to ensure functional integrity of the heart.This comprehensive examination underscores the therapeutic potential of enhancing cytokine secretion to mitigate adverse effects and promote recovery following MI,offering insights into possible interventions that could improve patient outcomes in clinical settings.

Water Modeling of Optimizing Tundish Flow Field

In the water modeling experiments, three cases were considered, i. e, , a bare tundish, a tundish equipped with a turbulence inhibitor, and a rectangular tundish equipped with weirs （dams） and a turbulence inhibitor. Comparing the RTD curves, inclusion separation, and the result of the streamline experiment, it can be found that the tundish equipped with weirs （dams） and a turbulence inhibitor has a great effect on the flow field and the inclusion separation when compared with the sole use or no use of the turbulent inhibitor or weirs （dams）. In addition, the enlargement of the distance between the weir and dam will result in a better effect when the tundish equipped with weirs （dam） and a turbulence inhibitor was used.

Experimental Study on Free Spanning Submarine Pipeline Under Dynamic Excitation

Seismic load has a significant effect on the response of a free spanning submarine pipeline when the pipeline is constructed in a seismically active region. The model experiment is performed on an underwater shaking table to simulate the response of submarine pipelines under dynamic input. In consideration of the effects of the terrestrial and submarine pipeline, water depth, support condition, distance from seabed, empty and full pipeline, and span on dynamic response, 120 groups of experiments are conducted. Affecting factors are analyzed and conclusions are drawn for reference. For the control of dynamic response, the span of a submarine pipeline is by far more important than the other factors. Meanwhile, the rosponse difference between a submarine pipeline under sine excitation and that under random excitation exists in experiments.

Classic mechanisms and experimental models for the anti-inflammatory effect of traditional Chinese medicine

Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases.Traditional Chinese medicine(TCM)has been used to treat inflammatory and related diseases since ancient times.According to the re-view of abundant modern scientific researches,it is suggested that TCM exhibit anti-inflammatory effects at different levels,and via multiple pathways with various targets,and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM.Currently,the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects pro-vide reference points and guidance for further research and development of TCM.Importantly,the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.

Experiment Study of Dynamics Response for Wind Turbine System of Floating Foundation

The floating foundation is designed to support a 1.5 MW wind turbine in 30 m water depth. With consideration of the viscous damping of foundation and heave plates, the amplitude-frequency response characteristics of the foundation are studied. By taking into account the elastic effect of blades and tower, the classic quasi-steady blade-element/momentum（BEM） theory is used to calculate the aerodynamic elastic loads. A coupled dynamic model of the turbine-foundationmooring lines is established to calculate the motion response of floating foundation under Kaimal wind spectrum and regular wave by using the FAST codes. The model experiment is carried out to test damping characteristics and natural motion behaviors of the wind turbine system. The dynamics response is tested by considering only waves and the joint action of wind and waves. It is shown that the wind turbine system can avoid resonances under the action of wind and waves. In addition, the heave motion of the floating foundation is induced by waves and the surge motion is induced by wind. The action of wind and waves is of significance for pitch.

Introduction of CMIP5 Experiments Carried out with the Climate System Models of Beijing Climate Center

The climate system models from Beijing Climate Center, BCC_CSM1.1 and BCC_CSM1.1-M, are used to carry out most of the CMIP5 experiments. This study gives a general introduction of these two models, and provides main information on the experiments including the experiment purpose, design, and the external forcings. The transient climate responses to the CO2 concentration increase at 1% per year are presented in the simulation of the two models. The BCC_CSM1.1-M result is closer to the CMIP5 multiple models ensemble. The two models perform well in simulating the historical evolution of the surface air temperature, globally and averaged for China. Both models overestimate the global warming and underestimate the warming over China in the 20th century. With higher horizontal resolution, the BCC_CSM1.1-M has a better capability in reproducing the annual evolution of surface air temperature over China.

Improved experimental model of hepatic cystic hydatid disease resembling natural infection route with stable growing dynamics and immune reaction

AIM To investigate a safer way to set up the disease model of cystic echinococcosis without contamination risk and develop a novel experimental murine model of hepatic cystic echinococcosis. METHODS C57 B/6 mice were injected with human protoscolices of three different concentrations via the portal vein. The mice were followed for 10 mo by ultrasound,gross anatomy,and pathological and immunological examinations. The protoscolex migration in the portal vein,hydatid cyst growth,host immune reaction,and hepatic histopathology were examined periodically.RESULTS The infection rates in the mice in the high,medium,and low concentration groups were 90%,100%,and 63.6%,respectively. The protoscolices migrated in the portal vein with blood flow,settled in the liver,and developed into orthotopic hepatic hydatid cysts,resembling the natural infection route and course.CONCLUSION We have established an improved experimental model of hepatic cystic echinococcosis with low biohazard risk but stable growing dynamics and immune reaction. It is especially useful for new anti-parasite medication trials against hydatid disease.

How do stream processes affect hazard exposure on alluvial fans? Insights from an experimental study

Alluvial fans are among the most privileged settlement areas in many mountain regions. These landforms are particularly dynamic being episodically affected by distributary processes generated by extreme flood events. Addressing risk assessment entails determining hazard exposure and unravelling how it might be related to process loading and to process dynamics once the flow becomes unconfined on the surface of alluvial fans. By following a ‘similarity of process concept’, rather than by attempting to scale a real-world prototype, we performed a set of 72 experimental runs on an alluvial fan model. Thereby, we considered two model layouts, one without a guiding channel and featuring a convex shape and the other one with a guiding channel, a bridge, and inclined but planar overland flow areas as to mirror an anthropic environment. Process magnitude and intensity parameters were systematically varied, and the associated biphasic distributary processes video recorded. For each experiment, the exposure was detected by mapping the exposed area in a GIS, thereby discerning between areas exposed to biphasic flows and the associated depositional phenomena or to the liquid flow phase only. Our results reveal that total event volume, sediment availability and stream power in the feeding channel, as well as depositional effects, avulsion, and channelization on the alluvial fan concur to determine the overall exposure. Stream process loading alone, even when rigorously defined in terms of its characterizing parameters, is not sufficient to exhaustively determine exposure. Hence, further developing reliable biphasic simulation models for hazard assessment on settled alluvial fans is pivotal.