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.Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry
Chung-Hsin CHEN ; Hsiang-Po HUANG ; Kai-Hsiung CHANG ; Ming-Shyue LEE ; Cheng-Fan LEE ; Chih-Yu LIN ; Yuan Chi LIN ; William J. HUANG ; Chun-Hou LIAO ; Chih-Chin YU ; Shiu-Dong CHUNG ; Yao-Chou TSAI ; Chia-Chang WU ; Chen-Hsun HO ; Pei-Wen HSIAO ; Yeong-Shiau PU ;
The World Journal of Men's Health 2025;43(2):376-386
Purpose:
Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles.
Materials and Methods:
Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion.
Results:
The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column.
Conclusions
Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.
3.Unmet Need for Palliative Care in Pediatric Hematology/Oncology Populations
Yi-Lun WANG ; Wan-Ju LEE ; Tsung-Yen CHANG ; Shih-Hsiang CHEN ; Chia-Chi CHIU ; Yi-Wen HSIAO ; Yu-Chuan WEN ; Tang-Her JAING
Clinical Pediatric Hematology-Oncology 2025;32(1):19-22
Background:
Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations.
Methods:
We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction.
Results:
During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study.
Conclusion
The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.
4.In-room cytologic evaluation by trained endosonographer for determination of procedure end in endoscopic ultrasound-guided fine needle biopsy of solid pancreatic lesions: a prospective study in Taiwan
Weng-Fai WONG ; Yu-Ting KUO ; Wern-Cherng CHENG ; Chia-Tung SHUN ; Ming-Lun HAN ; Chieh-Chang CHEN ; Hsiu-Po WANG
Clinical Endoscopy 2025;58(3):465-473
Background/Aims:
Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE).
Methods:
A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE).
Results:
We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%.
Conclusions
In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.
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.Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry
Chung-Hsin CHEN ; Hsiang-Po HUANG ; Kai-Hsiung CHANG ; Ming-Shyue LEE ; Cheng-Fan LEE ; Chih-Yu LIN ; Yuan Chi LIN ; William J. HUANG ; Chun-Hou LIAO ; Chih-Chin YU ; Shiu-Dong CHUNG ; Yao-Chou TSAI ; Chia-Chang WU ; Chen-Hsun HO ; Pei-Wen HSIAO ; Yeong-Shiau PU ;
The World Journal of Men's Health 2025;43(2):376-386
Purpose:
Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles.
Materials and Methods:
Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion.
Results:
The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column.
Conclusions
Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.
7.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.
8.Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry
Chung-Hsin CHEN ; Hsiang-Po HUANG ; Kai-Hsiung CHANG ; Ming-Shyue LEE ; Cheng-Fan LEE ; Chih-Yu LIN ; Yuan Chi LIN ; William J. HUANG ; Chun-Hou LIAO ; Chih-Chin YU ; Shiu-Dong CHUNG ; Yao-Chou TSAI ; Chia-Chang WU ; Chen-Hsun HO ; Pei-Wen HSIAO ; Yeong-Shiau PU ;
The World Journal of Men's Health 2025;43(2):376-386
Purpose:
Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles.
Materials and Methods:
Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion.
Results:
The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column.
Conclusions
Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.
9.Unmet Need for Palliative Care in Pediatric Hematology/Oncology Populations
Yi-Lun WANG ; Wan-Ju LEE ; Tsung-Yen CHANG ; Shih-Hsiang CHEN ; Chia-Chi CHIU ; Yi-Wen HSIAO ; Yu-Chuan WEN ; Tang-Her JAING
Clinical Pediatric Hematology-Oncology 2025;32(1):19-22
Background:
Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations.
Methods:
We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction.
Results:
During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study.
Conclusion
The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.
10.In-room cytologic evaluation by trained endosonographer for determination of procedure end in endoscopic ultrasound-guided fine needle biopsy of solid pancreatic lesions: a prospective study in Taiwan
Weng-Fai WONG ; Yu-Ting KUO ; Wern-Cherng CHENG ; Chia-Tung SHUN ; Ming-Lun HAN ; Chieh-Chang CHEN ; Hsiu-Po WANG
Clinical Endoscopy 2025;58(3):465-473
Background/Aims:
Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE).
Methods:
A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE).
Results:
We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%.
Conclusions
In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.

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