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 imp...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.展开更多
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 rem...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
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 chron...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.展开更多
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 bra...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.展开更多
Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the num...Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.展开更多
To predict the flutter dynamic pressure of a wind tunnel model before flutter test,an accurate Computational Fluid Dynamics/Computational Structural Dynamics(CFD/CSD)-based flutter prediction method is proposed under ...To predict the flutter dynamic pressure of a wind tunnel model before flutter test,an accurate Computational Fluid Dynamics/Computational Structural Dynamics(CFD/CSD)-based flutter prediction method is proposed under the conditions of a 2.4 m×2.4 m transonic wind tunnel with porous wall.From the CFD simulations of the flows through an inclined hole of this wind tunnel,the Nambu's linear porous wall model between the flow rate and the differential pressure is extended to the porous wall with inclined holes,so that the porous wall can be conveniently modeled as a boundary condition.According to the flutter testing approach for the current wind tunnel,the steady CFD calculation is conducted to achieve the required inlet Mach number.A timedomain CFD/CSD method is then employed to evaluate the structural response of the experimental model,and the critical flutter point is obtained by increasing the dynamic pressure step by step at a fixed Mach number.The present method is applied to the flutter calculations for a vertical tail model and an aircraft model tested in the current transonic wind tunnel.For both models,the computed flutter characteristics agree well with the experimental results.展开更多
Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the num...Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.展开更多
Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multi...Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multiple organ systems throughout the body.Our knowledge of the pathogenesis of AAV has increased considerably in recent years,involving cellular,molecular and genetic factors.Because of the controlled environment with no other confounding factors,animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects.However,the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients.The aim of this review is to overview the current status of animal models for AAV,outline the pros and cons of methods,and propose potential directions for future research.展开更多
Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(...Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.展开更多
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...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.展开更多
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 con...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.展开更多
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 studie...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.展开更多
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 t...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.展开更多
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. ...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.展开更多
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 ...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.展开更多
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-alp...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.展开更多
BACKGROUND: Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models ...BACKGROUND: Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy (AION). OBJECTIVE : To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), flash visual evoked potential (F-VEP), and histopathologically confirm its reliability. DESIGN: A randomized control tria SETTINGS : Department of Ophthalmology, Xi'an Fourth Hospital; Xi'an Institute of Ocular Fundus Diseases MATERIALS : The experiments were carried out in the research room of Xi'an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g, were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK (Military)2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed. The rats were randomly divided into blank control group (n =5), laser group (n =5), hematoporphyrin derivative (HPD) group and AION group (n =15), each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one. METHODS: In the AION group, the rats were injected with HPD (10 mg/kg) via caudal vein, and then the optic discs were exposed to krypton red (647 nm, 80 mV) for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red (647 rim, 80 mV) for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only injected with HPD (10 mg/kg) via caudal vein; Those in the blank control group were untouched. (1) Visual electrophysiological test: The F-VEP was used to evaluate the function of visual nerve. (2) FFA: After mydriasis and anesthesia as describe above, the fluorescein sodium parenteral solution (1 mL/kg) was injected v/a caudal vein and finished within about 3 s, the time of FFA was recorded from the beginning of injection, the video sight aimed at the optic disc and the surrounding area. (3) After mydriasis and anesthesia as describe above, the rats were examined with OCT. (4) Histological observation: After hematoxylin and eosin (HE) staining, the optic disc and surrounding blood vessels of retina were observed under light microscope at high power field. MAIN OUTCOME MEASURES: The results of fundus, FFA, visual electrophysiological test and OCT detection within 90 days after model establishment were observed. RESULTS: Of the 30 rats, 1 died after anesthesia in the laser group and 2 died in the AION group respectively, and finally 27 rats were involved in the analysis of results. (1) Changes in fundus: In the AION group, there was edema in upper optic disc and unclear boundary at 1 day after establishment, edema still could be observed at 6 days, and upper optic disc atrophied and appeared as pale at 90 days. (2) FFA results: In the AION group, early "low fluorescence", middle and late "high fluorescence" were observed in upper optic disc 1 day after model establishment, and there was "low fluorescence" at 6 days, and the low fluorescence could be observed all the time at 23 days. (3) Visual electrophysiological changes: In the AION group as compared with the control eyes, the experimental ones had prolonged F-VEP P100 latency [(71.65±8.81), (57.58±8.38) ms, t =3.148, P =0.012], and decreased wave amplitude [(4.77±1.90), (10.06±3.66) μV, t =4.082, P =0.003], and these changes lasted to 35 days after model establishment. (4) OCT results: In the AION group, the reflection surface of part nerve fiber layer was higher than the retina plane, the surface was rough and the thickness was increased at 6 days after model establishment. (5) Histopathological results: At 1 day after model establishment, part optic discs had highly edema, edema of nerve fibers, and loose tissue, also accompanied by the displacement of surrounding retina; At 23 days, the optic disc and surrounding nerve fiber layers became thinner, and the numbers of ganglion nuclei in the retina tissue sections were obviously decreased. These changes were not observed in the laser group, HPD group and blank control group. CONCLUSION : The changes of fundus, FFA, OCT, visual electrophysiology and histopathology confirmed that the krypton red laser irradiation (647 nm) at 2 hours after HPD was injected via caudal vein can establish more ideal animal models of AION.展开更多
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 i...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.展开更多
文摘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.
文摘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.
基金Supported by National Natural Science Foundation of China,No.82260133 and No.82370661the Academic and Technical Leader of major disciplines in Jiangxi Province,No.20225BCJ23021+2 种基金the Jiangxi Medicine Academy of Nutrition and Health Management,No.2022-PYXM-01the Natural Science Foundation of Jiangxi Province,No.20224ACB216004the Technological Innovation Team Cultivation Project of the First Affiliated Hospital of Nanchang University,No.YFYKCTDPY202202.
文摘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.
基金supported by the China Postdoctoral Science Foundation (no. 2020M670599)
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China(81825011,81930038,81961160738)Program of Shanghai Academic/Technology Research Leader(22XD1400800)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19030200)。
文摘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.
基金supported by grants from the from the Department of Defense Breast Cancer Research Program(CA171885)from the National Cancer Institute(U01CA184902)to Dr.Clarke.
文摘Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.
基金supported by the National Natural Science Foundation of China(No.11872212)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘To predict the flutter dynamic pressure of a wind tunnel model before flutter test,an accurate Computational Fluid Dynamics/Computational Structural Dynamics(CFD/CSD)-based flutter prediction method is proposed under the conditions of a 2.4 m×2.4 m transonic wind tunnel with porous wall.From the CFD simulations of the flows through an inclined hole of this wind tunnel,the Nambu's linear porous wall model between the flow rate and the differential pressure is extended to the porous wall with inclined holes,so that the porous wall can be conveniently modeled as a boundary condition.According to the flutter testing approach for the current wind tunnel,the steady CFD calculation is conducted to achieve the required inlet Mach number.A timedomain CFD/CSD method is then employed to evaluate the structural response of the experimental model,and the critical flutter point is obtained by increasing the dynamic pressure step by step at a fixed Mach number.The present method is applied to the flutter calculations for a vertical tail model and an aircraft model tested in the current transonic wind tunnel.For both models,the computed flutter characteristics agree well with the experimental results.
基金This work was supported by grants from the from the Department of Defense Breast Cancer Research Program(CA171885)from the National Cancer Institute(U01CA184902)to Dr.Clarke.
文摘Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.
基金the Ethics Committee of Tongji Hospital,Huazhong University of Science and Technology,China(TJ-IRB20191012).
文摘Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multiple organ systems throughout the body.Our knowledge of the pathogenesis of AAV has increased considerably in recent years,involving cellular,molecular and genetic factors.Because of the controlled environment with no other confounding factors,animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects.However,the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients.The aim of this review is to overview the current status of animal models for AAV,outline the pros and cons of methods,and propose potential directions for future research.
基金Supported by the Austrian EURASIA-PACIFIC UNINET Technology Scholarship,the Austrian Federal Ministry of Science and Research and the Austrian Federal Ministry of Health(GZ 402.000/0006-II/6b/2012)the National Basic Research Program of China(No.2014CB543203)
文摘Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.
基金Project(07JJ4016) supported by the Natural Science Foundation of Hunan Procvince,China
文摘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.
基金financial support from the National Key Research and Development Program of China (No.2023YFC2907501)the National Natural Science Foundation of China (No.52374106)the Fundamental Research Funds for the Central Universities (No.2023ZKPYNY01)。
文摘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.
基金supported by the Henan Medical Science and Technology Joint Building Program(No.LHGJ20230283)the Medical Science and Technology Research Project of Henan Province(No.SBGJ202103079).
文摘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.
基金This research is financially supported by the Science and Technology Foundation of Liaoning Province (Grant No.972240)
文摘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.
基金Project FONDECYT nr.1170657 titled “The flood memory of a river system:using both experimental and field-based approaches to unravel the role of unsteady flow and antecedent flows on sediment dynamics during floods” funded by CONICYT and led by Luca MaoProject FONDECYT nr.1170413 titled “Morphological impacts in rivers affected by volcanic eruptions.Chaiten and Calbuco:similar disturbance but different fluvial evolution?(PIROFLUV)” funded by CONICYT and led by Andrés Iroumé。
文摘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.
基金Supported by Xinjiang Key Lab of Xinjiang Science and Technology Bureau Xinjiang,No.2014KL002National Natural Science Foundation of China,No.81372425National S&T Major Project,No.SQ2018ZX100301
文摘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.
基金supported by National Institutes of Health grants AI070827 and CA33266American Cancer Society grant RSG-09-076-01 and the UIC Walter Payton Center GUILD
文摘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.
基金a grant from Scientific Research Fund of Shaanxi Department of Hygiene, No. 04AC1
文摘BACKGROUND: Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy (AION). OBJECTIVE : To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), flash visual evoked potential (F-VEP), and histopathologically confirm its reliability. DESIGN: A randomized control tria SETTINGS : Department of Ophthalmology, Xi'an Fourth Hospital; Xi'an Institute of Ocular Fundus Diseases MATERIALS : The experiments were carried out in the research room of Xi'an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g, were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK (Military)2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed. The rats were randomly divided into blank control group (n =5), laser group (n =5), hematoporphyrin derivative (HPD) group and AION group (n =15), each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one. METHODS: In the AION group, the rats were injected with HPD (10 mg/kg) via caudal vein, and then the optic discs were exposed to krypton red (647 nm, 80 mV) for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red (647 rim, 80 mV) for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only injected with HPD (10 mg/kg) via caudal vein; Those in the blank control group were untouched. (1) Visual electrophysiological test: The F-VEP was used to evaluate the function of visual nerve. (2) FFA: After mydriasis and anesthesia as describe above, the fluorescein sodium parenteral solution (1 mL/kg) was injected v/a caudal vein and finished within about 3 s, the time of FFA was recorded from the beginning of injection, the video sight aimed at the optic disc and the surrounding area. (3) After mydriasis and anesthesia as describe above, the rats were examined with OCT. (4) Histological observation: After hematoxylin and eosin (HE) staining, the optic disc and surrounding blood vessels of retina were observed under light microscope at high power field. MAIN OUTCOME MEASURES: The results of fundus, FFA, visual electrophysiological test and OCT detection within 90 days after model establishment were observed. RESULTS: Of the 30 rats, 1 died after anesthesia in the laser group and 2 died in the AION group respectively, and finally 27 rats were involved in the analysis of results. (1) Changes in fundus: In the AION group, there was edema in upper optic disc and unclear boundary at 1 day after establishment, edema still could be observed at 6 days, and upper optic disc atrophied and appeared as pale at 90 days. (2) FFA results: In the AION group, early "low fluorescence", middle and late "high fluorescence" were observed in upper optic disc 1 day after model establishment, and there was "low fluorescence" at 6 days, and the low fluorescence could be observed all the time at 23 days. (3) Visual electrophysiological changes: In the AION group as compared with the control eyes, the experimental ones had prolonged F-VEP P100 latency [(71.65±8.81), (57.58±8.38) ms, t =3.148, P =0.012], and decreased wave amplitude [(4.77±1.90), (10.06±3.66) μV, t =4.082, P =0.003], and these changes lasted to 35 days after model establishment. (4) OCT results: In the AION group, the reflection surface of part nerve fiber layer was higher than the retina plane, the surface was rough and the thickness was increased at 6 days after model establishment. (5) Histopathological results: At 1 day after model establishment, part optic discs had highly edema, edema of nerve fibers, and loose tissue, also accompanied by the displacement of surrounding retina; At 23 days, the optic disc and surrounding nerve fiber layers became thinner, and the numbers of ganglion nuclei in the retina tissue sections were obviously decreased. These changes were not observed in the laser group, HPD group and blank control group. CONCLUSION : The changes of fundus, FFA, OCT, visual electrophysiology and histopathology confirmed that the krypton red laser irradiation (647 nm) at 2 hours after HPD was injected via caudal vein can establish more ideal animal models of AION.
基金supported by the National Basic Research Program of China (973 Program) under No. 2010CB951903the National Science Foundation of China under Grant No. 41105054, 41205043the China Meteorological Administration under Grant No.GYHY201106022, GYHY201306048, CMAYBY2012-001
文摘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.