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.YOLOX-SwinT algorithm improves the accuracy of AO/OTA classification of intertrochanteric fractures by orthopedic trauma surgeons.
Xue-Si LIU ; Rui NIE ; Ao-Wen DUAN ; Li YANG ; Xiang LI ; Le-Tian ZHANG ; Guang-Kuo GUO ; Qing-Shan GUO ; Dong-Chu ZHAO ; Yang LI ; He-Hua ZHANG
Chinese Journal of Traumatology 2025;28(1):69-75
PURPOSE:
Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification.
METHODS:
We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the SPSS 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1.
RESULTS:
The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS.
CONCLUSION
In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.
Humans
;
Hip Fractures/diagnostic imaging*
;
Orthopedic Surgeons
;
Algorithms
;
Artificial Intelligence
7.New perspectives on microbiome-dependent gut-brain pathways for the treatment of depression with gastrointestinal symptoms: from bench to bedside.
Menglin LIU ; Genhao FAN ; Lingkai MENG ; Kuo YANG ; Huayi LIU
Journal of Zhejiang University. Science. B 2025;26(1):1-25
Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.
Humans
;
Gastrointestinal Microbiome/physiology*
;
Depression/microbiology*
;
Gastrointestinal Diseases/physiopathology*
;
Brain
;
Animals
;
Brain-Gut Axis
;
Gastrointestinal Tract/microbiology*
8.Effects of high intensity interval training on glucose metabolism, cortisol and sleep quality among college students with comorbid depressive symptoms and obesity
Chinese Journal of School Health 2025;46(12):1721-1726
Objective:
To explore the intervention effects of high intensity interval training (HIIT) on glucose metabolism, cortisol (Cor), and sleep quality among college students with comorbid depressive symptoms and obesity, so as to provide a reference for improving sleep quality among college students with comorbid depressive symptoms and obesity.
Methods:
In March 2023, 45 college students with comorbid depressive symptoms and obesity were recruited and randomly assigned to an exercise group ( n =23) and a control group ( n =22) by random number table method. The exercise group received HIIT intervention for 12 weeks, three times a week, while the control group received no intervention. Blood samples were collected from participants to measure fasting insulin (FINS), fasting blood glucose (FBG), homeostatic model assessment of insulin resistance (HOMA-IR), Cor, and Pittsburgh Sleep Quality Index (PSQI) before and after intervention. Statistical analysis was performed using t-test, repeated measures analysis of variance (ANOVA), simple effect analysis.
Results:
The repeated measures ANOVA revealed statistically significant time×group interaction effects for body composition (weight, body mass index, percentage of body fat, fat mass, waist to hip ratio), depressive symptoms, PSQI scores and its subdimensions (subjective sleep quality, sleep onset time, sleep efficiency, sleep disorders, daytime dysfunction), as well as FBG, FINS, and HOMA-IR between the exercise group and control group before and after intervention ( F =7.10-53.38, all P <0.05). Simple effect analysis showed that compared to the control group, the exercise group demonstrated significant improvements in body composition (body mass index, fat mass, waist to hip ratio), depressive symptoms, PSQI scores and its sub dimensions (subjective sleep quality, sleep onset time, sleep efficiency, sleep disorders, daytime dysfunction), FBG, FINS, HOMA-IR, and Cor (all P <0.05).
Conclusion
HIIT can improve the sleep quality of college students with comorbid depressive symptoms and obesity by enhancing glucose metabolism and regulating Cor levels.
9.Expression purification,antibody preparation,and subcellular localization analysis of Toxoplasma gondii thioredoxin 20
Yuyi SHI ; Shengqi GAN ; Che LIU ; Ziwen CHENG ; Kuo CHENG ; Baoling YANG ; Dawei WANG
Journal of Jilin University(Medicine Edition) 2025;51(6):1595-1606
Objective:To express,purify,prepare antibodies,and analyze the subcellular localization of Toxoplasma gondii thioredoxin 20(Trx20),and to provide the reference for the development of Toxoplasma gondii vaccine.Methods:Bioinformatics-related websites and software were used to perform bioinformatics analysis of the Trx20 protein;specific primers were designed to amplify the target fragment and construct the prokaryotic expression vector;the protein was expressed in vitro and purified;experimental animals were immunized to prepare antibodies;enzyme-linked immunosorbent assay(ELISA)method was used to detect the titer of the polyclonal antibodies;Western blotting method was used to verify the specificity and sensitivity of the antibodies and to determine the natural expression of the protein;immunofluorescence assay(IFA)was used to analyze the subcellular localization of the protein.Results:The bioinformatics analysis results showed that Trx20 protein was a relatively stable hydrophilic protein with a molecular formula of C2172H3412N548O616S20,containing 424 amino acids,a predicted relative molecular mass of 47 700,and a theoretical isoelectric point of 8.55;it was predicted that the protein had one signal peptide,no transmembrane region,contained one domain named"Thioredoxin like Superfamily",and had 35 phosphorylation sites,one N-glycosylation site,and 17 antigenic determinants;in the secondary structure,alpha-helices accounted for 41.51%of the total amino acids,and random coils accounted for 39.86%;the recombinant plasmids pET-28a-Trx20 and pGEX-4T-1-Trx20 were successfully constructed,and the soluble recombinant protein was expressed and purified;polyclonal antibodies were successfully prepared with a titer as high as 1:64 000,and they specifically recognized the endogenous Trx20 protein in Toxoplasma gondii;the subcellular localization results showed that Trx20 protein was widely distributed in the cytoplasm of the parasite.Conclusion:Toxoplasma gondii Trx20 protein is a secretory protein containing phosphorylation/glycosylation modification sites and a thioredoxin domain,and it is localized in the cytoplasm of the parasite.
10.Effects of Jieyu Huatan Xiaoyu Formula on Clinical Efficacy and Nrf2-Keap Signaling Pathway in Patients with Gastric Precancerous Lesions of Liver-Stomach Disharmony Type
Yuxin CHEN ; Kuo YANG ; Huayi LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(11):2697-2704
Objective To investigate the clinical efficacy of Jieyu Huatan Xiaoyu Formula(JYHTXYF)in patients with gastric precancerous lesions(GPL)of liver-stomach disharmony type and to observe its effects on the nuclear factor erythroid 2-related factor 2(Nrf2)-Kelch-like ECH-associated protein 1(Keap1)signaling pathway.Methods A prospective study enrolled 100 GPL patients with liver-stomach disharmony syndrome treated at the Department of Gastroenterology,Affiliated Hospital of Tianjin Academy of Chinese Medicine from August 2023 to August 2024.Participants were randomized into control group(n=50,treated with Moluodan Pills)and trial group(n=50,treated with JYHTXYF decoction)for 6 months.Traditional Chinese medicine(TCM)syndrome scores,gastroscopic pathological scores,serum superoxide dismutase(SOD)and malondialdehyde(MDA)levels,along with Nrf2-Keap pathway-related gene/protein expressions were assessed before and after treatment.Results(1)Regarding clinical efficacy,after 6 months of treatment,the total effective rate was 94.00%(47/50)in the trial group and 76.00%(38/50)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy of the trial group was significantly superior to that of the control group(P<0.05).(2)In terms of traditional Chinese medicine(TCM)syndrome scores,after treatment,the scores for TCM syndromes such as epigastric pain,gastric distension,belching,and poor appetite decreased in both groups compared to those before treatment(P<0.05),and the reduction in the trial group was significantly superior to that in the control group(P<0.01).(3)Regarding gastroscopic pathological scores,after treatment,the scores for gastric mucosal atrophy,intestinal metaplasia,dysplasia,and chronic inflammation decreased in both groups compared to those before treatment(P<0.05),and the reduction in the trial group was significantly greater than that in the control group(P<0.01).(4)In terms of oxidative stress indicators,after treatment,SOD levels increased in both groups compared to before treatment(P<0.05),while serum MDA levels decreased(P<0.05).The magnitude of increase in serum SOD levels and the magnitude of decrease in serum MDA levels in the trial group were significantly greater than those in the control group(P<0.05 or P<0.01).(5)Regarding the expression levels of genes related to the Nrf2-Keap signaling pathway,after treatment,the relative mRNA expression levels of Nrf2,NAD(P)H quinone dehydrogenase 1(NQO1),and heme oxygenase-1(HO-1)in gastric mucosal tissue increased in both groups compared to those before treatment(P<0.05),and the increase in the trial group was significantly greater than that in the control group(P<0.01).(6)Regarding the expression levels of proteins related to the Nrf2-Keap signaling pathway,after treatment,the relative protein expression levels of Nrf2,HO-1,and mitochondrial superoxide dismutase(SOD2)in gastric mucosal tissue increased in both groups compared to those before treatment(P<0.05),and the increase in the trial group was significantly greater than that in the control group(P<0.01).Conclusion JYHTXYF effectively improves TCM syndromes and gastroscopic pathology in GPL patients of liver-stomach disharmony type,elevates serum antioxidant enzyme levels,and upregulates the expression of genes and proteins associated with the Nrf2-Keap1 signaling pathway,thereby enhancing clinical efficacy.The study will provide novel insights and approaches for the treatment of gastric precancerous lesions.


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