1.Establishment and evaluation of a lipopolysaccharide-induced acute respiratory distress syndrome model in minipigs
Chuang-Ye WANG ; Ran WANG ; Jian ZHANG ; Ling-Xiao QIU ; Bin QING ; Heng YOU ; Jin-Cheng LIU ; Bin WANG ; Nan-Bo WANG ; Jia-Yu LI ; Xing LIU ; Shuang WANG ; Jin HU ; Jian WEN ; Quan LI ; Xiao-Ou HUANG ; Kun ZHAO ; Shuang-Lin LIU ; Gang LIU ; Mei-Ju WANG ; Qing XIANG ; Hong-Mei WU ; Xiao-Rong SUN ; Tao GU ; Dong ZHANG ; Qi LI ; Zhi XU
Medical Journal of Chinese People's Liberation Army 2025;50(9):1154-1161
Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.
2.Effect of Huangqi Shengmai Yin on myocardial fibrosis in rats with acute myocardial infarction by adjusting P2X7R/NLRP3 pathway
Yi-Jie MA ; You-Jian ZHANG ; Ji-Pei WANG ; Dan-Dan LI ; Jin-Ge JIN
Acta Anatomica Sinica 2025;56(6):713-720
Objective To investigate the effect of Huangqi Shengmai Yin(HSY)on myocardial fibrosis in rats with acute myocardial infarction(AMI)by adjusting P2X purinoceptor 7(P2X7R)/NOD-like receptor protein 3(NLRP3)pathway.Methods Sixty rats were divied into a sham operation group and model group(5 groups),with 10 rats in each group.The AMI rat model was constructed by ligating the left anterior descending branch and randomly grouped into AMI group,the HSY-low group(intragastric administration of 1.6 ml/kg HSY),the HSY group(intragastric administration of 6.2 ml/kg HSY),the compound miltiorhiza group(intragastric administration of 300 mg/kg),and the HSY-high+P2X7R agonist-ATP group(intragastric administration of 6.2 ml/kg HSY,and tail vein administration of 10 mmol/L ATP).After the intervention,cardiac function,myocardial injury and inflammatory factor markers were detected.The tissue sections were prepared to examine pathological changes,myocardial fibrosis,type Ⅰ and type Ⅲ collagen(COL1A1,COL3A1).Western blotting was performed to detecte the protein expression of P2X7R,NLRP3,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and the expression of activated Caspase-1.Results Compared with the sham surgery group,the AMI group showed an increase in the left ventricular end diastolic diameter(LVEDD),the coatent of brain natriuretic peptide(BNP)and cardiac troponin I(cTn I),fibrosis volume fraction,the positive expression of COL1A1,COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P<0.05),and a decrease in left ventricular ejection fraction(LVEF)(P<0.05).The HSY-low group,HSY-high groups,and compound miltiorhiza group showed a decrease in LVEDD,the content of BNP and cTn I,fibrosis volume fraction,the positive expression of COL1A1 and COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P<0.05),and an increase in LVEF than these in the AMI group(P<0.05).The HSY-high+ATP group showed an increase in LVEDD,the content of BNP,cTn I,fibrosis volume fraction,the positive expression of COL1A1 and COL3A1,TNF-α,IL-1β,P2X7R,NLRP3,and activated Caspase-1 proteins(P<0.05),and a decrease in LVEF than those in the HSY-high group(P<0.05).Conclusion HSY inhibits P2X7R/NLRP3 pathway to alleviate myocardial fibrosis in AMI rats.
3.Single nucleotide polymorphism typing of Yersinia pestis in natural plague foci around Qinghai Lake
Sheng LI ; Juan JIN ; Jian HE ; Xiao-yan YANG ; Ji-xiang BAI ; You-quan XIN ; Li ZHANG ; Xiao-lu ZHANG ; Wen-qi DU ; Wei LI
Chinese Journal of Zoonoses 2025;41(6):592-596
This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.
4.Circulating immunological transcriptomic profile identifies DDX3Y and USP9Y on the Y chromosome as promising biomarkers for predicting response to programmed death 1/programmed death ligand 1 blockade.
Liting YOU ; Zhaodan XIN ; Feifei NA ; Min CHEN ; Yang WEN ; Jin LI ; Jiajia SONG ; Ling BAI ; Jianzhao ZHAI ; Xiaohan ZHOU ; Binwu YING ; Juan ZHOU
Chinese Medical Journal 2025;138(3):364-366
5.Digital Phenotyping of Rare Endocrine Diseases Across International Data Networks and the Effect of Granularity of Original Vocabulary
Seunghyun LEE ; Namki HONG ; Gyu Seop KIM ; Jing LI ; Xiaoyu LIN ; Sarah SEAGER ; Sungjae SHIN ; Kyoung Jin KIM ; Jae Hyun BAE ; Seng Chan YOU ; Yumie RHEE ; Sin Gon KIM
Yonsei Medical Journal 2025;66(3):187-194
Purpose:
Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model.
Materials and Methods:
Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea.
Results:
The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK).
Conclusion
Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.
6.Digital Phenotyping of Rare Endocrine Diseases Across International Data Networks and the Effect of Granularity of Original Vocabulary
Seunghyun LEE ; Namki HONG ; Gyu Seop KIM ; Jing LI ; Xiaoyu LIN ; Sarah SEAGER ; Sungjae SHIN ; Kyoung Jin KIM ; Jae Hyun BAE ; Seng Chan YOU ; Yumie RHEE ; Sin Gon KIM
Yonsei Medical Journal 2025;66(3):187-194
Purpose:
Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model.
Materials and Methods:
Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea.
Results:
The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK).
Conclusion
Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.
7.Evaluation and prospect of clinical pharmacist instructor training reform oriented toward enhancing clinical teaching competence
Li YOU ; Jiancun ZHEN ; Jing BIAN ; Zhuo WANG ; Yunyun YANG ; Jin LU ; Jing LIU
China Pharmacy 2025;36(17):2085-2091
OBJECTIVE To summarize the implementation experiences of the China Hospital Association’s Clinical Pharmacist Instructor Training Program Reform, and to evaluate the effectiveness of the reform, thus continuously enhancing the quality and standards of clinical pharmacist instructor training. METHODS The study drew on project evaluation methodologies to summarize the main characteristics of the comprehensive system and new model for clinical pharmacist instructor training established through the reform by literature review. The “learning assessment” and “reaction assessment” were conducted by using Kirkpatrick’s four-level model of evaluation in order to evaluate the effectiveness of the clinical pharmacist instructor training reform through statistically processing and analyzing the performance data and teaching evaluation data of the instructor participants. Based on problem and trend analysis, the future development directions were anticipated for the reform of clinical pharmacist instructor training. RESULTS & CONCLUSIONS The latest round of clinical pharmacist instructor training reform initiated by the Chinese Hospital Association had initially established a four-pronged training system encompassing “recruitment, training, assessment, and management”. It had also forged a training 。 model “oriented towards enhancing clinical teaching competency, with practical learning and skill-based assessment conducted on clinical teaching sites as its core”. Following a period of over three years of gradual reform, the new training system and model became increasingly mature. In both 2023 and 2024, the participants achieved relatively high average total scores in their initial completion assessments [with scores of (84.05± 5.83) and (85.82±4.35) points, respectively]. They also reported a strong sense of gain from the training reform [with self- perceived gain scores of (4.80±0.44) and (4.85±0.39) points, respectively]. The operation and implementation effects of the reform were generally satisfactory. In the future, clinical pharmacist instructor training reforms should continue to address the issues remaining from the current phase, while aligning with global trends in pharmacy education and industry development. Additionally, sustained exploration and practice will be carried out around the core objective of “enhancing clinical teaching competence”.
8.Single nucleotide polymorphism typing of Yersinia pestis in natural plague foci around Qinghai Lake
Sheng LI ; Juan JIN ; Jian HE ; Xiao-yan YANG ; Ji-xiang BAI ; You-quan XIN ; Li ZHANG ; Xiao-lu ZHANG ; Wen-qi DU ; Wei LI
Chinese Journal of Zoonoses 2025;41(6):592-596
This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.
9.Digital Phenotyping of Rare Endocrine Diseases Across International Data Networks and the Effect of Granularity of Original Vocabulary
Seunghyun LEE ; Namki HONG ; Gyu Seop KIM ; Jing LI ; Xiaoyu LIN ; Sarah SEAGER ; Sungjae SHIN ; Kyoung Jin KIM ; Jae Hyun BAE ; Seng Chan YOU ; Yumie RHEE ; Sin Gon KIM
Yonsei Medical Journal 2025;66(3):187-194
Purpose:
Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model.
Materials and Methods:
Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea.
Results:
The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK).
Conclusion
Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.
10.Digital Phenotyping of Rare Endocrine Diseases Across International Data Networks and the Effect of Granularity of Original Vocabulary
Seunghyun LEE ; Namki HONG ; Gyu Seop KIM ; Jing LI ; Xiaoyu LIN ; Sarah SEAGER ; Sungjae SHIN ; Kyoung Jin KIM ; Jae Hyun BAE ; Seng Chan YOU ; Yumie RHEE ; Sin Gon KIM
Yonsei Medical Journal 2025;66(3):187-194
Purpose:
Rare diseases occur in <50 per 100000 people and require lifelong management. However, essential epidemiological data on such diseases are lacking, and a consecutive monitoring system across time and regions remains to be established. Standardized digital phenotypes are required to leverage an international data network for research on rare endocrine diseases. We developed digital phenotypes for rare endocrine diseases using the observational medical outcome partnership common data model.
Materials and Methods:
Digital phenotypes of three rare endocrine diseases (medullary thyroid cancer, hypoparathyroidism, pheochromocytoma/paraganglioma) were validated across three databases that use different vocabularies: Severance Hospital’s electronic health record from South Korea; IQVIA’s United Kingdom (UK) database for general practitioners; and IQVIA’s United States (US) hospital database for general hospitals. We estimated the performance of different digital phenotyping methods based on International Classification of Diseases (ICD)-10 in the UK and the US or systematized nomenclature of medicine clinical terms (SNOMED CT) in Korea.
Results:
The positive predictive value of digital phenotyping was higher using SNOMED CT-based phenotyping than ICD-10-based phenotyping for all three diseases in Korea (e.g., pheochromocytoma/paraganglioma: ICD-10, 58%–62%; SNOMED CT, 89%). Estimated incidence rates by digital phenotyping were as follows: medullary thyroid cancer, 0.34–2.07 (Korea), 0.13–0.30 (US); hypoparathyroidism, 0.40–1.20 (Korea), 0.59–1.01 (US), 0.00–1.78 (UK); and pheochromocytoma/paraganglioma, 0.95–1.67 (Korea), 0.35–0.77 (US), 0.00–0.49 (UK).
Conclusion
Our findings demonstrate the feasibility of developing digital phenotyping of rare endocrine diseases and highlight the importance of implementing SNOMED CT in routine clinical practice to provide granularity for research.

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