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Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal model with Pancreatic Tumor

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Chinese Journal of Integrative Medicine 2024年第1期30卷 85-95页

作者： JIAO Ju-ying CHENG Chien-shan CAO Zhang-qi CHEN Lian-yu CHEN Zhen Department of Integrative Oncology Fudan University Shanghai Cancer CenterShanghai(200032)China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai(200032)China

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted Animal model to study this core syndrome in vivo. The shortage of Animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and Animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer Animal model.

关键词： cancer Chinese medicine syndrome ZHENG dampness-heat syndrome Animal model pancreatic tumor evaluation methods

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Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an Animal model

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Zoological Research 2022年第3期43卷 301-318页

作者： Guang Wang Yong-Feng Wang Jiang-Lan Li Ru-Ji Peng Xin-Yin Liang Xue-Dong Chen Gui-Hua Jiang Jin-Fang Shi Yang-Hu Si-Ma Shi-Qing Xu School of Biology and Basic Medical Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu 215123China Department of Clinical Laboratory First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215006China

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration(PPC)and is often clinically complicated by malignant diseases or severe infections.At present,however,research on the molecular mechanism underlying high PPC(HPPC)is scant.Here,an Animal model of primary hyperproteinemia was constructed in an invertebrate(Bombyx mori)to investigate the effects of HPPC on circulating blood cells.Results showed that HPPC affected blood cell homeostasis,leading to increased reactive oxygen species levels,and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway.HPPC induced the proliferation of blood cells,mainly granulocytes,by activating the Janus kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway.Supplementation with the endocrine hormone active substance 20 E significantly reduced the impact of HPPC on blood cell homeostasis.Thus,we identified a novel signaling pathway by which HPPC affects blood cell homeostasis,which differs from hyperglycemia,hyperlipidemia,and hypercholesterolemia.In addition,we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.

关键词： Animal model Blood cell homeostasis High plasma protein concentration(HPPC) JAK/STAT pathway Programmed cell death

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Animal model-based simulation training for three emergent and urgent operations of penetrating thoracic injuries

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Chinese Journal of Traumatology 2023年第1期26卷 41-47页

作者： Wen-Qiong Du Xin Zhong Ren-Qing Jjiang Zhao-Wen Zong Yi-Jun Jia Zhao Ye Xiao-Lin Zhou State Key Laboratory of Trauma Burn and Combined InjuryDepartment for Combat Casualty Care TrainingTraining Base for Army Health CareArmy Medical UniversityChongqing400037China State Key Laboratory of Trauma Burn and Combined InjuryDepartment for Combat Casualty Care TrainingTraining Base for Army Health Care&Department of OrthopedicsXinqiao HospitalArmy Medical UniversityChongqing400037China

Purpose:To develop Animal models of penetrating thoracic injuries and to observe the effects of the Animal model-based training on improving the trainees’performance for emergent and urgent thoracic surgeries.Methods:With a homemade machine,Animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage,urgent sternotomy,and emergent thoracotomy.Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of Animal models.Five operation teams from basic-level hospitals(group A)and five operation teams from level III hospitals(group B)were included to be trained and tested.Testing standards for the operations were established after thorough literature review,and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards.Tests were carried out after the training.Pre-and post-training performances were compared.Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches.Results:Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%.After literature review,testing standards were established,and expert questionnaire results showed that the scientific score was 7.30±1.49,and the feasibility score was 7.50±0.89.Post-training performance was significantly higher in both group A and group B than pre-training performance.Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury.Conclusions:Animal model-based simulation training established in the current study could improve the trainees’performance for emergent and urgent thoracic surgeries,especially of the surgical teams from basic-level hos

关键词： Penetrating thoracic injuries Emergent operations Urgent operations Simulation training Animal model

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Enzymatic hydrolysis of silkworm pupa and its allergenicity evaluation by Animal model with different immunization routes

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Food Science and Human Wellness 2023年第3期12卷 774-782页

作者： Yan Dai Meijia Huang Yujuan Xu Lixia Mu Jingyan Gao Hongbing Chen Zhihua Wu Anshu Yang Yong Wu Xin Li State Key Laboratory of Food Science and Technology Nanchang UniversityNanchang 330047China School of Food Science and Technology Nanchang UniversityNanchang 330047China Sericultural and Agri-Food Research Institute Guangdong Academy of Agricultural Sciences Key Laboratory of Functional FoodsMinistry of Agriculture and Rural AffairsGuangdong Key Laboratory of Agricultural Products ProcessingGuangzhou 510610China Sino-German Joint Research Institute Nanchang UniversityNanchang 330047China

Silkworm pupa is a nourishing food with high nutritional value,but its consumption has been greatly limited given its allergenicity.Enzyme hydrolytic technique is recognized as an effective method to reduce the allergenicity of protein.In this study,we aimed to investigate the effect of enzymolysis on the allergenicity of silkworm pupa.Crude silkworm pupa protein was extracted through alkali extraction and acid precipitation,which included 5 proteins with the molecular weights ranging from 34 kDa to 76 kDa,and silkworm pupa were then hydrolyzed by alkaline protease.The allergenicity of silkworm pupa protein and its enzymatic hydrolysates was evaluated by establishing BALB/c mice model,and the mice were immunized via intragastric gavage and intraperitoneal injection,respectively.The results indicated that the intraperitoneal inj ection immunization route induced more by detecting with antibodies,histamine and Th2-related cytokines.Moreover,mice treated with silkworm pupa protein peptide displayed no obvious allergic symptoms,indicating that enzyme hydrolytic technique could significantly reduce the allergenicity of silkworm pupa.

关键词： Silkworm pupa Silkworm pupa peptides Enzymatic hydrolysis Allergenicity Immunization Animal model

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Mid-Term Preliminary Results for Safety and Patency of the Occlutech Atrial Flow Regulator in an Animal model

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Congenital Heart Disease 2022年第3期17卷 269-280页

作者： Kamel Shibbani Daniel McLennan Dunbar Ivy Gareth Morgan Division of Cardiology Department of PediatricsStead Family Children’s HospitalUniversity of Iowa Hospitals and ClinicsIowa CityUSA Division of Cardiology Department of PediatricsMedical College of WisconsinMilwaukeeUSA Division of Cardiology Heart InstituteChildren’s Hospital of ColoradoUniversity of Colorado at DenverAuroraUSA

Objective:The Atrial Flow Regulator(AFR)is a double disc device made of self-expanding Nitinol wire mesh,structured around a central lumen.Once deployed via the transfemoral route,the device stents the atrial septum leaving a preselected fixed diameter atrial communication.We sought to evaluate the mid-term performance of the AFR by implanting the device in 5 healthy porcine hearts to assess safety and patency of the device fenestration over a period of 150 days.Method:Five AFR devices were implanted in 5 female Yucatan adult minipigs.The animals were survived to 150 days with periodic assessments at days+3,+30,+60,+90,+120,and+150.These assessments consisted of transesophageal echocardiography and fluoroscopic evaluation.The animals were sacrificed at day+150.Histological and pathological assessments were carried out to characterize neointimal tissue growth,inflammation,thrombus formation,endothelial coverage,endothelial maturity,and the presence of any luminal thrombus.Result:There were no unscheduled deaths.Patency was maintained in all 5 animals across the 150-day study.There was no statistically significant difference in the lumen diameter over the study duration.Neointimal growth was mild to moderate in all specimens and occurred mostly on the surfaces of the device in direct contact with the atrial septum.There was no evidence of any significant inflammatory response on routine blood work or by imaging or histological assessment.Scanning electron microscope(SEM)examination showed nearly complete surface coverage with endothelial tissue.The animals were in a healthy condition for the duration of the study with no attributable pathology and no adverse effects noted on distant organs in any of the 5 animals.Conclusion:As a continuation of our earlier work,this 150-day midterm animal study provides important safety and feasibility information.Our preliminary results show that the AFR is both safe and effective in maintaining a sustainable atrial level communication for the duration of the study.

关键词： Atrial flow regulator Animal model atrial septal defect interventional cardiology device

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Lower respiratory tract samples are reliable for severe acute respiratory syndrome coronavirus 2 nucleic acid diagnosis and Animal model study

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Zoological Research 2021年第2期42卷 161-169页

作者： Ren-Rong Tian Cui-Xian Yang Mi Zhang Xiao-Li Feng Rong-Hua Luo Zi-Lei Duan Jian-Jian Li Jia-Fa Liu Dan-Dan Yu Ling Xu Hong-Yi Zheng Ming-Hua Li Hong-Li Fan Jia-Li Wang Xing-Qi Dong Yong-Tang Zheng Key Laboratory of Animal models and Human Disease Mechanisms of the Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Center for Biosafety Mega-Science Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Yunnan Infectious Diseases Hospital KunmingYunnan 650301China

Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) and coronavirus disease 2019(COVID-19) continue to impact countries worldwide.At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-Co V-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-Co V-2-infected monkeys. We also detected anti-SARS-Co V-2 antibodies in the above clinical and Animal model samples to identify a reliable approach for the accurate diagnosis of SARS-Co V-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-Co V-2 immunoglobulin M(Ig M) and G(Ig G) antibodies were not detected in6.90% of COVID-19 patients. Furthermore,integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-Co V-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus,SARS-Co V-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-Co V-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.

关键词： COVID-19 SARS-CoV-2 Diagnosis Animal model

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Era of the 4D Animal model

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Animal models and Experimental Medicine 2023年第2期6卷 178-182页

作者： Lihong Zhang Jindan Guo Jiangning Liu NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

Revealing the entire dynamics of pathogenesis is critical for understanding,preventing and treating human disease but is limited by systematic clinical sampling.This drawback can be overcome with Animal model studies.Recent advances in phenotyping,omics and bioinformatics technologies promote the development of the 4D Animal model to simulate and digitally display the spatiotemporal landscapes of phenotypes and molecular dynamics in human diseases and reveal novel targets for diagnosis and therapy.In this commentary,the origin,supporting technologies,content,function and application,and advantages of 4D Animal models over clinical studies and traditional Animal models,as well as their limitations,are presented.

关键词： Animal model database digitally display human diseases spatiotemporal landscapes

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Effect of lymphotoxin blockage on different stages of Sjogren's syndrome in an Animal model

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Rheumatology & Autoimmunity 2022年第2期2卷 76-81页

作者： Alexander Jacob Long Shen Jing He Kelly Nealon Jessy J.Alexander Julian L.Ambrus Jr Department of Medicine SUNY at Buffalo School of MedicineBuffaloNew YorkUSA Department of Rheumatology and Immunology Peking University People's HospitalBeijingChina

Background:Lymphotoxin(LT)is an important mediator in Sjogren's syndrome(SS),both in patients and in Animal models.Deletion of the LT alpha gene prevented the development of disease manifestations in the interelukin alpha transgenic mouse(IL14αTG)mouse model of SS.Aims:The current study was designed to evaluate the use of LT inhibitors at different stages of the disease in IL14αTG mice.Materials and Methods:IL14αTG mice were treated with anti‐LTa monoclonal antibody,LTb receptor‐immunoglobulin fusion protein(LTBR‐Ig)or isotype control during different stages of disease and analysis of salivary gland function,immunoglobulins,autoantibodies and histology of internal organs performed.Results and Discussion:The inhibitors were very effective in maintaining salivary gland function and preventing infiltration of the glands with lymphocytes when used in the early stages of the disease.Blocking LT at later stages of the disease did not recover salivary gland function but was still effective in limiting extra glandular manifestations including eye disease and tumor development.Some differences were noted in the effectiveness of anti‐LTαversus LTBR‐Ig in limiting particular disease manifestations.Conclusion:LT inhibitors deserve further investigation in the management of SS at whatever stage is identified.

关键词： Animal model lymphotoxin Sjogren's syndrome

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Preclinical in vivo research of magnesium-based implants for fracture treatment: A systematic review of Animal model selection and study design

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Journal of Magnesium and Alloys 2021年第2期9卷 351-361页

作者： Yu Sun Heike Helmholz Regine Willumeit-Römera Division of Metallic Biomaterials Institute of Materials ResearchHelmholtz-Zentrum Geesthacht21502 GeesthachtGermany Department of Orthopedics First Hospital of China Medical UniversityShenyang 110001China

Background:Degradable magnesium implants are promising for clinical fracture treatment,providing less stress-shielding mechanical support and superior bone-strengthening benefits to traditional materials.The quality of preclinical research is essential for developing Mg implants;however,there are considerable variations in the model selection and study design in published studies,posing challenges for safe and effective clinical translation of lab discoveries.Objective:The purpose of this systematic review is to investigate the current progress on in vivo research of Mg implants for fracture treatment,focusing on model selection,Mg materials,implant design,methodological and analyzing techniques,aiming to provide comprehensive guidance for future preclinical research.Materials and methods:Pub Med and Embase online databases were searched to identify researches investigating Mg implants in Animal models of fracture from 1960 to December 2019,using a combination of keywords:magnesium and fracture.Eligible studies were included without language restriction.Data extraction was conducted for qualitative analysis.Meta-analysis was not performed due to extensive heterogeneities among studies.Results:Twenty studies published from 2014 to 2019 were included.Publication information,Animal model,methodological quality,implants preparation,and evaluation techniques were extracted.The methodological assessment revealed low to high risk of bias among studies.Both rodent and non-rodent species were selected,and the anatomical sites for inducing fractures included both cranial-facial and limb bones.Pure Mg and alloys with or without surface modification were evaluated,covering implant designs of both intra-medullary and extra-medullary fixation.Radiological and histological evaluations were commonly conducted.Conclusions:Published in vivo evidence confirmed the role of Mg-based implants in promoting fracture healing.However,considering heterogeneity in animal selection,implant preparation,and evaluation methods,there still lacks

关键词： Magnesium Implant Fracture Animal model Study design Biomaterial

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Guinea pigs as an Animal model for sciatic nerve injury

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Neural Regeneration Research 2017年第3期12卷 452-457页

作者： Malik Abu Rafee Amarpal Prakash Kinjavdekar Hari Prasad Aithal Sajad Ahmad Wani Irfan Ahmad Bhat Division of Surgery Indian Veterinary Research InstituteIzatnagarBareillyUPIndia Division of Veterinary Biotechnology Indian Veterinary Research InstituteIzatnagarBareillyUPIndia Division of Veterinary Physiology Indian Veterinary Research InstituteIzatnagarBareillyUPIndia

The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes.To address the problem,this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies.A crush injury was inflicted to the sciatic nerve of the left limb,which led to significant decrease in the pain perception and neurorecovery up to the 4th weak.Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury.A 3.49 ± 0.35 fold increase in expression of neuropilin 1（NRP1） gene and 2.09 ± 0.51 fold increase in neuropilin 2（NRP2） gene were recorded 1 week after nerve injury as compared to the normal nerve.Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30 th day.Histopathologically,vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers.Gastrocnemius muscle also showed degenerative changes.Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve.The findings suggest that guinea pigs could be used as an alternative Animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.

关键词： nerve regeneration Guinea pigs Animal model sciatic nerve injury foot print length neuropilin histopathology neural regeneration

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