1.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
2.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
3.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
4.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
5.An animal model of severe acute respiratory distress syndrome for translational research
Kuo‑An CHU ; Chia‑Yu LAI ; Yu‑Hui CHEN ; Fu‑Hsien KUO ; I.‑Yuan CHEN ; You‑Cheng JIANG ; Ya‑Ling LIU ; Tsui‑Ling KO ; Yu‑Show FU
Laboratory Animal Research 2025;41(1):81-92
Background:
Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.
Results:
In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation (SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.
Conclusions
This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
6.Shuangshen Ningxin Capsules Regulates Mitochondrial Fission and Fusion to Alleviate Myocardial Ischemia-reperfusion Injury in Rats
Gaojie XIN ; Yuanyuan CHEN ; Zixin LIU ; Yue YOU ; Ce CAO ; Aoao WANG ; Hongxu MENG ; Xiao HAN ; Jianxun LIU ; Lei LI ; Jianhua FU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):87-94
ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules (SSNX) in alleviating myocardial ischemia-reperfusion injury (MIRI) in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley (SD) rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group, model group, SSNX group (90 mg·kg-1) and trimetazidine group (5.4 mg·kg-1). The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were detected by micro method. Changes in mitochondrial membrane potential (△Ψm) and the degree of mitochondrial permeability transition pore (mPTP) opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate (ATP) level was detected by the luciferase assay. The messenger ribonucleic acid (mRNA) and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 (DRP1), mitochondrial fission 1 protein (FIS1), optic atrophy protein 1 (OPA1), mitochondrial outer membrane fusion protein 1 (MFN1), and MFN2 were detected by real-time polymerase chain reaction (real-time PCR) and Western blot. ResultCompared with the sham operation group, the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP, the level of △Ψm and ATP content decreased, the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased, and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group,SSNX significantly increased serum SOD activity, reduced MDA content, increased intracellular ATP level and △Ψm, reduced the opening level of mPTP, downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1, and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1, and increases the expressions of fusion related factors OPA1 and MFN1, inhibiting mitochondrial fission and increasing mitochondrial fusion, thereby alleviating MIRI.
7.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
8.Introduction and application of non-parametric regression method in medical research
Ya-Hang LIU ; Yong-Fu YU ; Guo-You QIN
Fudan University Journal of Medical Sciences 2024;51(2):280-284
This article introduced the basic theory of non-parametric regression and its application in medical and public health research for methodological reference.We conducted Cox proportional hazard models with restricted cubic splines using chronic disease management data from a Center for Disease Control and Prevention.We aimed to explore the separate and combined effects of mean fasting blood glucose level and glucose variability on all-cause mortality among individuals with type 2 diabetes.A non-linear association was observed between glucose variability and the risk of all-cause mortality.The association between glucose variability and all-cause mortality was stronger at higher mean fasting blood glucose levels compared to lower levels.The non-parametric regression methods comprehensively explored dose-response relationships between continuous exposure and outcome,revealing the combined effects of continuous exposures,which provided recommendations for targeted interventions.The method showed promising application value in medical and public health research.
9.Clinical Features and Prognostic Analysis of Newly Diagnosed Diffuse Large B-cell Lymphoma Combined with Hemophagocytic Syndrome
Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Fei LIU ; Qiao-Lin CHEN ; Qi-Ke ZHANG
Journal of Experimental Hematology 2024;32(2):466-469
Objective:To compare the clinical features and prognosis between newly diagnosed diffuse large B-cell lymphoma(DLBCL)patients with and without hemophagocytic syndrome(HPS).Methods:The clinical data of 45 DLBCL patients in Gansu Provincial Hospital from January 2012 to December 2021 were retrospectively analyzed.The patients were divided into HPS group(15 cases)and non-HPS group(30 cases).The clinical features and prognosis of the two groups were compared,and survival analysis was performed using Kaplan-Meier method.Results:Patients with HSP were mostly characterized by fever,cytopenia and splenomegaly.The levels of ferritin and soluble CD25 increased in all patients.The level of fibrinogen decreased in 66.67%patients,while triglyceride increased in 53.33%patients,and bone marrow hemophagocytosis occurred in 80.00%patients.Compared with non-HSP group,the proportions of patients with advanced stage(Ann Arbor stage Ⅲ/Ⅳ)and lactate dehydrogenase(LDH)≥ 240 U/L were higher in HSP group(both P<0.05).The median survival time of HSP group was 8.0 months,which was significantly shorter than 45.5 months of non-HSP group(P<0.001).Conclusion:The DLBCL patients with HPS have later Ann Arbor stage,higher LDH and shorter overall survival time compared with patients without HPS.
10.Clinical Characteristics and Prognosis of Patients with Primary Bone Marrow Lymphoma
Qiao-Lin CHEN ; You-Fan FENG ; Yuan FU ; Fei LIU ; Wen-Jie ZHANG ; Yang CHEN ; Xiao-Fang WEI ; Qi-Ke ZHANG
Journal of Experimental Hematology 2024;32(4):1117-1120
Objective:To investigate the clinical characteristics and prognosis of primary bone marrow lymphoma.Methods:The clinical data of 6 patients with primary bone marrow lymphoma admitted to Gansu Provincial People's Hospital from February 2011 to March 2023 were collected,and their clinical characteristics and prognosis were retrospectively analyzed and summarized.Results:The median age of 6 patients was 61(52-74)years old.There were 2 males and 4 females.All patients had fever and abnormal blood routine examination.Physical examination and imaging examination showed no lymphadenopathy,no extranodal lesions in lung,gastrointestinal,liver and spleen,skin,etc.After strict exclusion of systemic lymphoma involvement in the bone marrow,the diagnosis was confirmed by bone marrow examination,5 cases were primary myeloid diffuse large B-cell lymphoma and 1 case was primary myeloid peripheral T-cell lymphoma(NOS).1 case abandoned treatment,5 cases received CHOP-like or combined R regimen,including 1 case of autologous stem cell transplantation.4 cases died and 2 case survived.The median OS was 5.5(1-36)months.Conclusion:The prognosis of primary marrow lymphoma is poor,and bone marrow-related examination is an important means of diagnosis.Diffuse large B-cell lymphoma is the most common histomorphologic and immune subtype,and autologous hematopoietic stem cell transplantation may improve the prognosis.

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