1.Construction and Evaluation of Mouse Models Simulating Immune Checkpoint Inhibitor-Associated Pneumonitis
Zhiqun GONG ; Xiwu RAO ; Tianyi ZHANG ; Rongchen WU ; Mingnan YE ; Chunxi JIANG ; Sumei WANG ; Yanjuan ZHU ; Xiaoshu CHAI
Laboratory Animal and Comparative Medicine 2026;46(4):498-506
ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.
2.Analysis of Animal Models of Lumbar Spinal Stenosis Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Miao HE ; Xuxing ZHANG ; Gang WU ; Yi ZHOU ; Hao RAO ; Xiangyu HU
Laboratory Animal and Comparative Medicine 2026;46(4):541-552
Lumbar spinal stenosis (LSS) is a common disabling condition in the elderly, and its clinical assessment relies not only on imaging and neurofunctional indicators but also on traditional Chinese medicine (TCM) syndrome differentiation. To evaluate the concordance between existing LSS animal models and clinical characteristics of TCM and Western medicine, clarify their advantages and limitations, and explore their translational potential, Chinese and English databases, including CNKI, Wanfang Data, PubMed, and Web of Science, are searched using combinations of the terms "lumbar spinal stenosis," "model," "guideline," "consensus," and "norm" from inception to the end of June 2025. After screening, a total of 21 publications are included, of which 15 report animal experimental studies, and 6 are guidelines, consensus statements, or normative documents. Based on these, the existing modeling methods are summarized, diagnostic indicators are extracted from clinical guidelines and expert consensus, and clinical concordance is evaluated using an assessment system proposed in the relevant literature. The results show that the existing animal models are categorized into three concordance levels: high (laminectomy/spinous process removal with filling; laminectomy/spinous process + ligament/muscle removal with filling; autologous bone backfilling), moderate (nylon tape dural binding method, adjustable screws, fixation combined with removal of ligament/muscle), and low (balloon compression method, adjustable balloon compression method, bipedal standing, ligament/muscle resection, steel wire cerclage method). Overall, current animal models of LSS generally perform well in terms of structural construction but show clear limitations in replicating clinical diagnostic logic and TCM syndromes. Future research should enhance syndrome phenotype collection and enrich TCM-based evaluation systems based on existing models. Additionally, multifactorial integrated modeling strategies should be introduced to extend the depth of syndrome-level simulation. This study aims to analyze LSS animal models that can faithfully recapitulate disease pathogenesis, conform to clinical realities of both Western medicine and TCM clinical practice, and have broad application potential, so as to narrow the translational gap between experimental findings and clinical practice.
3.Analysis of sarcopenia prevalence and related factors in community-dwelling older adults based on C-MSRA-7 combined with Ishii score
Lijun WANG ; Ping WU ; Haimin XU ; Kewen CHENG ; Fen RAO ; Miaomiao YAO ; Yu ZHANG
Chinese Journal of Clinical Medicine 2026;33(4):643-650
Objective To investigate the prevalence and related factors of sarcopenia among non–bedridden older adults in the community of Baoshan District using the China mini sarcopenia risk assessment 7 (C-MSRA-7) combined with Ishii scoring system. Methods The older individuals consulting at 20 community health stations in Baoshan District between April 2025 and June 2025 were enrolled. Data were collected using a general information questionnaire, a dietary and lifestyle habits survey, the C-MSRA-7, and the mini nutritional assessment-short form (MNA-SF). Handgrip strength and anthropometric measurements were also obtained. Individuals with both Ishii score and C-MSRA-7 results positive were classified into the sarcopenia risk group, while the remaining participants were assigned to the non–sarcopenia risk group. Differences in lifestyle habits, dietary patterns, and nutritional status between the two groups were compared. Results A total of 2 611 valid questionnaires were retrieved. Univariate analysis showed statistically significant differences in alcohol consumption, physical activity frequency, body mass index (BMI), nutritional status, activities of daily living, and regularity of three meals in sarcopenia risk group (n=486) and non–sarcopenia risk group (n=2 125, P<0.05). Logistic regression analysis showed that advanced age (75–84 years: OR=2.55, 95%CI 2.03–3.21; ≥85 years: OR=3.98, 95%CI 2.24–7.07), underweight status (OR=2.19, 95%CI 1.50–3.19), weight loss>2 kg (OR=4.52, 95%CI 2.68–7.64) past 3 months, lack of regular physical activity (OR=1.77, 95%CI 1.24–2.52) , and alcohol consumption (OR=1.48, 95%CI 1.07–2.05) were independent risk factors for sarcopenia (P<0.05). Behaviors related to healthy diet, including daily milk consumption (OR=0.40, 95%CI 0.30–0.52), regular three meals (OR=0.56, 95%CI 0.41–0.78), and high-quality protein intake (OR=0.70, 95%CI 0.52–0.94), were protective factors (P<0.05). Conclusions Sarcopenia among community–dwelling, non–bedridden older adults is closely associated with physical activity levels, dietary habits, and nutritional status. Early identification of individuals at risk, enhanced nutritional education, and timely implementation of nutritional interventions and exercise programs are recommended for this population.
4.TMAO promotes disorders of lipid metabolism in psoriasis.
Rao LI ; Boyan HU ; Manyun MAO ; Wangqing CHEN ; Wu ZHU
Journal of Central South University(Medical Sciences) 2025;50(3):331-343
OBJECTIVES:
Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis.
METHODS:
An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.
RESULTS:
IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder.
CONCLUSIONS
TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals
;
Methylamines/blood*
;
Mice
;
Psoriasis/chemically induced*
;
Lipid Metabolism/drug effects*
;
Humans
;
Male
;
Liver/metabolism*
;
Female
;
Oxygenases/genetics*
;
Disease Models, Animal
;
Lipid Metabolism Disorders/etiology*
;
Adult
;
Mice, Inbred C57BL
5.Single-cell and spatial transcriptomic analysis reveals that an immune cell-related signature could predict clinical outcomes for microsatellite-stable colorectal cancer patients receiving immunotherapy.
Shijin YUAN ; Yan XIA ; Guangwei DAI ; Shun RAO ; Rongrong HU ; Yuzhen GAO ; Qing QIU ; Chenghao WU ; Sai QIAO ; Yinghua XU ; Xinyou XIE ; Haizhou LOU ; Xian WANG ; Jun ZHANG
Journal of Zhejiang University. Science. B 2025;26(4):371-392
Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4+ T, regulatory CD4+ T, CD4+ Th17, exhausted CD8+ T, cytotoxic CD8+ T, proliferated CD8+ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans
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Colorectal Neoplasms/drug therapy*
;
Male
;
Female
;
Immunotherapy
;
Middle Aged
;
Aged
;
Tumor Microenvironment/immunology*
;
Retrospective Studies
;
Microsatellite Instability
;
Transcriptome
;
Single-Cell Analysis
;
Programmed Cell Death 1 Receptor/immunology*
;
Gene Expression Profiling
;
Immune Checkpoint Inhibitors/therapeutic use*
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Adult
;
Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*
6.Increasing trends of hyperglycemia and diabetes in treatment-naive people living with HIV in Shenzhen from 2013 to 2019: An emerging health concern.
Liqin SUN ; Haipeng ZHU ; Man RAO ; Fang ZHAO ; Yang ZHOU ; Lukun ZHANG ; Xia SHI ; Jianwei WU ; Yun HE ; Hongzhou LU ; Jiaye LIU
Chinese Medical Journal 2025;138(16):2043-2045
7.Research progress on pentacyclic triterpenoids in medicinal Ilex species and their pharmacological activities.
Yu-Ling LIU ; Yi-Ran WU ; Bao-Lin WANG ; Xiao-Wei SU ; Qiu-Juan CHEN ; Yi RAO ; Shi-Lin YANG ; Li-Ni HUO ; Hong-Wei GAO
China Journal of Chinese Materia Medica 2025;50(12):3252-3266
Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry*
;
Plants, Medicinal/chemistry*
;
Pentacyclic Triterpenes/pharmacology*
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/pharmacology*
;
Humans
;
Animals
8.Morphological classification of postero-superior protuberance of calcaneus and its relationship with Haglund deformity.
Lei ZHANG ; Man ZHANG ; Lu JIANG ; Lei HUANG ; Yu WU ; Rao LENG ; Houyin SHI ; Guoyou WANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):592-597
OBJECTIVE:
To explore the morphological characteristics of the postero-superior protuberance of the calcaneus and to explore its relationship with Haglund malformation.
METHODS:
Ankle lateral X-ray films of 391 hospitalized patients between May 2021 and June 2024 were retrospectively collected. The morphological parameters of the postero-superior protuberance of the calcaneus were measured, including the length of the base, the height of the base, and the tip angle of the postero-superior protuberance of the calcaneus, and the morphological types were classified according to the above parameters, including the peak type, the hill type, and the flat type. The related parameters of Haglund malformation were measured, including Fowler-Philipp angle (FPA), calcaneal pitch angle (CPA), parallel pitch line (PPL), Chauveaux-Liet angle (CLA), and X/Y ratio (total calcaneal length/length of greater tuberosity of calcaneus). The differences of the morphological parameters of the postero-superior protuberance of the calcaneus and the related indicators of Haglund deformity among the three types and between the males and the females were compared and analyzed, and the differences of the positive numbers of the related indicators of Haglund deformity among the three types were compared.
RESULTS:
According to the morphological parameters of the postero-superior protuberance of the calcaneus, there were 64 cases of peak type, 245 cases of hill type, and 82 cases of flat type. There was no significant difference in the length of the base of the postero-superior protuberance of the calcaneus, CPA, CLA, and X/Y ratio among the three types ( P>0.05). Among the three types, the peak type had the largest FPA and the flat type had the smallest ( P<0.05); the peak type had the smallest tip angle of the postero-superior protuberance of the calcaneus and the flat type had the largest ( P<0.05); the positive rate of PPL in the hill type was significantly higher than that in the peak type and flat type ( P<0.05); the height of the base of the postero-superior protuberance of the calcaneus in the flat type was the smallest ( P<0.05). FPA, CPA, CLA, PPL, and X/Y ratio were positive in 2, 42, 172, 142, and 77 patients, respectively. There was no significant difference in the number of positive Haglund deformity indicators among the three types ( P>0.05). There was no significant difference between male and female patients in the tip angle of the postero-superior protuberance of the calcaneus, FPA, the positive rate of PPL, and X/Y ratio ( P>0.05). The length and the height of the base of the postero-superior protuberance of the calcaneus, CPA, and CLA in male patients were significantly higher than those in female patients ( P<0.05).
CONCLUSION
The postero-superior protuberance of the calcaneus can be divided into three types: the peak type, the hill type, and the flat type. The peak type is more likely to suffer from Haglund deformity, and the males are more likely to suffer from Haglund deformity than the females.
Humans
;
Calcaneus/anatomy & histology*
;
Male
;
Female
;
Retrospective Studies
;
Adult
;
Middle Aged
;
Adolescent
;
Young Adult
;
Radiography
;
Child
;
Aged
9.Multimodal Data-Driven Prediction of Gynecological Surgery Duration
Yong HUANG ; Zhilin YONG ; Banghua WU ; Xueying ZHOU ; Xiaoling LANG ; Yuming LI ; Miye WANG ; Qingke SHI ; Li RAO
Journal of Sichuan University (Medical Sciences) 2025;56(5):1392-1398
Objective Focusing on gynecological surgery,we constructed a prediction model for surgical duration by extracting features from unstructured surgical planning texts and integrating multimodal data via artificial intelligence technology.Methods The clinical data of 34 614 patients who underwent gynecologic surgeries at West China Second University Hospital,Sichuan University between January 2022 and October 2024 were collected.An embedding-transformer model was constructed to convert surgical planning texts into a one-dimensional numerical feature,referred to as the step feature.The predictive value of the step feature was assessed by comparing the performance improvements of linear regression,random forest,eXtreme Gradient Boosting(XGBoost),support vector regression,K-nearest neighbor regression,and artificial neural network algorithms in two scenarios—with and without the step feature as an input.The out-of-sample prediction accuracy of the models was assessed using mean absolute error(MAE),root mean squared error(RMSE),and R-squared(R2).Furthermore,the model interpretability was examined using SHapley Additive exPlanations(SHAP)values.Results SHAP results showed that the step feature had the highest predictive contribution.Temporal factors in surgical scheduling also influenced gynecological surgery duration.The XGBoost model demonstrated optimal performance on the test set,significantly improving prediction accuracy with a 40.43%increase in R2,while reducing MAE and RMSE by 21.27%and 20.13%,respectively,compared to the baseline model without the step feature.Conclusion The embedding-transformer model developed in this study effectively extracts features from surgical planning texts and enhances the predictive performance of machine learning models.The XGBoost prediction model can assist hospital administrators in implementing more refined management of gynecological surgeries and improving the utilization efficiency of surgical resources.
10.Construction and application of nursing quality evaluation index system for percutaneous radiofrequency ablation of liver cancer under the background of disease diagnosis related groups
Xufang HUANG ; Qiaohong WU ; Jianting MAO ; Qiaoying RAO ; Jia SONG ; Jing LI ; Weifeng XIA
Journal of Interventional Radiology 2025;34(2):192-196
Objective Based on the background of disease diagnosis related groups(DRGs)in public hospitals to construct the nursing quality evaluation index system for percutaneous radiofrequency ablation(PRFA)of liver cancer so as to improve the nursing quality for PRFA of liver cancer.Methods Using three-dimensional quality model and through interview,literature analysis,two rounds of Delphi expert letter inquiry and analytic hierarchy process,the evaluation standard of PRFA nursing quality of liver cancer was established,and its effect was validated in clinical practice.Results The evaluation index system of PRFA nursing quality for liver cancer was constructed,which included 3 first-level indexes,9 second-level indexes and 22 third-level indexes.After clinical application,the incidence of intraoperative and postoperative moderate-severe pain,the incidence of high fever,and the 24-hour number of times required care in the intervention group were lower than those in the control group(P<0.05),the incidence of postoperative Ⅲ degree vomiting in the intervention group was remarkably lower than that in the control group(P<0.01),and the average hospitalization days in the intervention group were less than those in the control group(P<0.05),and the average hospitalization expense in the intervention group was lower than that in the control group,but the difference was not statistically significant(P>0.05).Conclusion The PRFA nursing quality evaluation index system for liver cancer is scientific and practical,which is helpful for improving the outcome of patients and promoting the quality of nursing.

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