1.Advances in perioperative nutritional management for patients with esophageal cancer
Zuyu ZHANG ; Bo YANG ; Rong NIU ; Jijun XUE ; Jian CHEN ; Dong LI ; Wentao ZHAO ; Wenfeng HAN ; Yue BAI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):157-162
Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.
2.Mechanism of drug-containing serum of Dianxianqing granules in inhibiting microglial ferroptosis
Guangkun FAN ; Yue QI ; Jixian WANG ; Wei CHEN ; Chunpeng XIA ; Yihang WANG ; Yue ZHAO ; Yang AN
China Pharmacy 2026;37(3):317-323
OBJECTIVE To explore the potential mechanism by which drug-containing serum of Dianxianqing granules (DXQ) inhibits microglial ferroptosis. METHODS Male SD rats were given normal saline and Dianxianqing granules solution via intragastric administration to prepare normal serum and DXQ, respectively. Mice microglia BV2 cells were collected and successfully transfected with a negative control small interfering RNA (si-NC), and then they were included in the si-NC group and cultured under normal conditions. Cells successfully transfected with small interfering RNA targeting glutathione peroxidase 4 (GPX4) (si-GPX4) were divided into the si-GPX4 group, the CsA group (treated with 1 μmol/L cyclosporine A), and the DXQ- L, DXQ-M and DXQ-H groups (treated with 5%, 7% and 10% DXQ, respectively). These groups were subsequently treated with their corresponding drug solutions and ferroptosis inducer Erastin (10 μmol/L). The intracellular levels of total iron ions, glutathione (GSH), reactive oxygen species (ROS), and the expression of mitochondrial superoxide were determined in each group after 48 h of treatment. Additionally, mitochondrial membrane potential, the opening degree of mitochondrial permeability transition pore (MPTP), and mRNA expressions of GPX4 and cyclophilin D (CypD) were detected. Furthermore, the expressions of ferroptosis-related proteins[GPX4, transferrin receptor 1 (TfR1) and ferritin heavy chain 1 (FTH1)], as well as MPTP-related proteins [adenine nucleotide translocator (ANT), cytochrome C (CytC), mitochondrial calcium uniporter (MCU) and CypD] were assessed. RESULTS Compared with si-NC group, the levels of total iron ions and ROS, the expression level of mitochondrial superoxide, the opening degree of MPTP, protein and its mRNA expressions of CypD as well as protein expressions of TfR1 and MCU were increased or up-regulated significantly (P<0.01); however, GSH content, mitochondrial membrane potential, protein and mRNA expressions of GPX4, and protein expressions of FTH1, ANT and CytC were decreased or down-regulated significantly (P<0.01). Compared with the si-GPX4 group, the cells in the DXQ-M, DXQ-H groups showed a general improvement in the above quantitative indicators (P<0.01 or P<0.05). CONCLUSIONS DXQ can enhance antioxidant capacity by activating the GSH/GPX4 pathway, regulate the expressions of TfR1 and FTH1 protein to correct iron ion homeostasis, inhibit excessive opening of MPTP to improve mitochondrial function, and ultimately suppress microglial ferroptosis.
3.Analysis of plasma metabonomic characteristics of type 2 diabetes mellitus patients with turbid toxin accumulation syndrome
Ziqi ZHAO ; Pai PANG ; Yue REN ; Bin WANG ; Yuntao MA ; Qianjing YANG ; Shentao WU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):34-42
Objective:
To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome.
Methods:
One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website.
Results:
There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways.
Conclusion
Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.
4.Efficacy of Fufang Lingjiao Jiangya Pills with Different Proportions of Goat Horn Replacing Antelope Horn on Spontaneous Hypertensive Rats
Tengjian WANG ; Wanlu ZHAO ; Yang YU ; Yan LIU ; Kun CAO ; Zheyuan LIN ; Yue WU ; Lilan LUO ; Weizhi LAI ; Zhaohuan LOU ; Qiaoyan ZHANG ; Quanlong ZHANG ; Luping QIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):68-78
ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats (SHR). In this experiment, 50 SHR rats were randomly grouped as follows: model (n=8), captopril (0.01 g·kg-1) (n=6), low-dose blank Fufang Lingjiao Jiangya pills (0.342 g·kg-1) (n=6), high-dose blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1) (n=6), low-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), high-dose antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6), low-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.378 g·kg-1) (n=6), and high-dose goat horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1) (n=6). Additionally, 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration, 3 h post administration, and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions, 48 SHR rats were randomly grouped as follows: model, blank Fufang Lingjiao Jiangya pills (0.684 g·kg-1), antelope horn-containing Fufang Lingjiao Jiangya pills (0.756 g·kg-1), 2× goat horn-containing Fufang Lingjiao Jiangya pills (0.824 g·kg-1), 4× goat horn Fufang Lingjiao Jiangya pills (0.969 g·kg-1), and 6× goat horn Fufang Lingjiao Jiangya pills (1.112 g·kg-1). The normal group included 8 WKY rats, and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks, and blood pressure was recorded at various time points (pre-administration, 3 h post administration, and on days 4, 7, 10, and 14 of administration). Serum levels of angiotensin-converting enzyme (ACE), angiotensin Ⅱ(Ang Ⅱ), renin, and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart, kidney, and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2, angiotensin Ⅱ type 1 receptor (AT1R), and angiotensinogen (AGT) in the kidney tissue were determined by Western blot, while the expression of nuclear factor (NF)-κB p65 and Toll-like receptor 4 (TLR4) in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group, all treatment groups showed lowered blood pressure (P<0.05, P<0.01), and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group, the model group showed elevated serum levels of ACE, Ang Ⅱ, renin, and IL-6, while the elevations were declined in the Fufang Lingjiao Jiangya pills groups (P<0.05, P<0.01). Pathological changes in the heart, kidney, and thoracic aorta were alleviated in all the treatment groups, with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R, AGT, NF-κB p65, and TLR4 and up-regulated protein levels of ACE2 (P<0.05, P<0.01) compared with model group, with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system (RAAS) and TLR4/NF-κB signaling pathways.
5.Latent class analysis and influencing factor study of work-related musculoskeletal disorders among operating room nurses in tertiary hospitals
Xiaogui TANG ; Li LI ; Yue ZHAO ; Ningning HU ; Feng FU ; Boya LI ; Mengru YANG ; Yinglan LI
Journal of Environmental and Occupational Medicine 2025;42(3):293-301
Background Work-related musculoskeletal disorders (WMSDs), as one of the major occupational health issues worldwide, have shown an increasing positive rate year by year. Due to the unique demands of work, operating room nurses exhibit a higher positive rate of WMSDs compared to other occupational groups, necessitating active attention and intervention. Objective To estimate the prevalence of WMSDs among operating room nurses in tertiary hospitals, explore the characteristics and latent categories of WMSDs, and analyze the influencing factors associated with the occurrence of WMSDs. Method Using a randomized cluster sampling method, operating room nurses from nine tertiary hospitals in Urumqi were selected as study participants between December 2023 and January 2024. Data were collected through a general information questionnaire, an ergonomic questionnaire for operating room nurses, and the Chinese Musculoskeletal Disorders Questionnaire. Latent class analysis was employed to examine the patterns of WMSDs among the nurses, while chi-square test and multinomial logistic regression were utilized to analyze the influencing factors of WMSDs. Result A total of 411 valid questionnaires were collected in this survey. The positive rate of WMSDs among operating room nurses in the tertiary hospitals of Urumqi over the past year was 91.9%. The positive rates, ordered from highest to lowest by body region, were neck (79.1%), shoulders (70.3%), and lower back (68.1%). The operating room nurses were categorized into three distinct groups by latent class analysis: multi-site pain group, neck-shoulder-back pain group, and neck and lower back pain group. The results of the multinomial logistic regression models revealed that gender, job strain level, ergonomic load level in the operating room, and exposure to cold or drafty working conditions or not were significant influencing factors for reporting WMSDs among operating room nurses. Specifically, having less than 5 years of work experience, low ergonomic load level, low job strain, and moderate job strain were identified as protective factors against WMSDs. Conversely, exposure to cold or drafty working environments and being female were identified as risk factors for WMSDs. The logistic regression models also indicated that compared to the neck-lower back pain group, the neck-shoulder-back pain group had a higher probability of reporting low job strain (OR=0.168, 95%CI: 0.029, 0.968) and being female (OR=4.847, 95%CI: 2.506, 9.378). In contrast, when comparing to the neck-lower back pain group, the multi-site pain group had a higher probability of reporting, low-level ergonomic workload (OR=0.079, 95%CI: 0.015, 0.412), low job strain (OR=0.019, 95%CI: 0.002, 0.145), moderate job strain (OR=0.080, 95%CI: 0.016, 0.401), high job strain (OR=0.132, 95%CI: 0.027, 0.647), less than 5 years of work experience (OR=0.173, 95%CI: 0.044, 0.683), being female (OR=2.424, 95%CI: 1.130, 5.200), and exposure to cold or drafty working environments (OR=3.277, 95%CI: 1.657, 6.481). Conclusion The positive rate WMSDs among operating room nurses in tertiary hospitals is notably high in Urumqi, with distinct co-occurrence characteristics observed within the population. To mitigate the risk of WMSDs, it is essential to implement targeted health education and prevention training programs tailored to different patterns of WMSDs. Additionally, improving working conditions, optimizing human resource allocation , and other proactive measures should be undertaken. These efforts will effectively reduce the incidence of WMSDs among operating room nurses and safeguard their occupational health.
6.Development and validation of the “Questionnaires on the Knowledge, Attitudes, and Practices of College Students in Response to Public Health Emergencies”
Hong JIANG ; Shuli MA ; Yufeng ZHANG ; Yue ZHAO ; Xinling YANG
China Occupational Medicine 2025;52(1):33-39
Objective To develop the "Questionnaires on the Knowledge, Attitudes, and Practices of College Students in Response to Public Health Emergencies" and validate its reliability and validity. Methods The initial questionnaire was developed according to literature review, expert consultations, and one-on-one interviews with students and educators. A total of 43 college students were selected as the pre-test subjects using the convenience sampling method. The final version of the questionnaire was developed using item analysis and expert consultations. A total of 682 college students were selected as the validation subjects using the cluster sampling method. The exploratory factor analysis and confirmatory factor analysis were used to assess the reliability and validity of the questionnaire. Results The final version of the questionnaire consisted of three dimensions: knowledge, practice, and attitude, with 5, 10, 7 items, respectively. The KMO test value for the questionnaire was 0.804, with Bartlett′s test of sphericity showing a chi-square value of 2 000.557 (P<0.01). The content validity index for each item ranged from 0.894 to 1.000, with the overall content validity index for the questionnaire being 0.966 and 0.973. The exploratory factor analysis identified three common factors, with a cumulative variance contribution rate of 54.1%. The result of confirmatory factor analysis showed good model fit, with model fit index, comparative fit index, normed fit index, incremental fit index, Tucker-Lewis Index, root mean square error of approximation of 2.960, 0.930, 0.940, 0.930, 0.950 and 0.070, respectively. The Cronbach's α coefficient for the questionnaire was 0.772, split-half reliability was 0.604, and test-retest reliability was 0.905. Conclusion The "Questionnaires on the Knowledge, Attitudes, and Practices of College Students in Response to Public Health Emergencies" demonstrates good reliability, and it is suitable for widespread application.
7.Prediction of Pulmonary Nodule Progression Based on Multi-modal Data Fusion of CCNet-DGNN Model
Lehua YU ; Yehui PENG ; Wei YANG ; Xinghua XIANG ; Rui LIU ; Xiongjun ZHAO ; Maolan AYIDANA ; Yue LI ; Wenyuan XU ; Min JIN ; Shaoliang PENG ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):135-143
ObjectiveThis study aims to develop and validate a novel multimodal predictive model, termed criss-cross network(CCNet)-directed graph neural network(DGNN)(CGN), for accurate assessment of pulmonary nodule progression in high-risk individuals for lung cancer, by integrating longitudinal chest computed tomography(CT) imaging with both traditional Chinese and western clinical evaluation data. MethodsA cohort of 4 432 patients with pulmonary nodules was retrospectively analyzed. A twin CCNet was employed to extract spatiotemporal representations from paired sequential CT scans. Structured clinical assessment and imaging-derived features were encoded via a multilayer perceptron, and a similarity-based alignment strategy was adopted to harmonize multimodal imaging features across temporal dimensions. Subsequently, a DGNN was constructed to integrate heterogeneous features, where nodes represented modality-specific embeddings and edges denoted inter-modal information flow. Finally, model optimization was performed using a joint loss function combining cross-entropy and cosine similarity loss, facilitating robust classification of nodule progression status. ResultsThe proposed CGN model demonstrated superior predictive performance on the held-out test set, achieving an area under the receiver operating characteristic curve(AUC) of 0.830, accuracy of 0.843, sensitivity of 0.657, specificity of 0.712, Cohen's Kappa of 0.417, and F1 score of 0.544. Compared with unimodal baselines, the CGN model yielded a 36%-48% relative improvement in AUC. Ablation studies revealed a 2%-22% increase in AUC when compared to simplified architectures lacking key components, substantiating the efficacy of the proposed multimodal fusion strategy and modular design. Incorporation of traditional Chinese medicine (TCM)-specific symptomatology led to an additional 5% improvement in AUC, underscoring the complementary value of integrating TCM and western clinical data. Through gradient-weighted activation mapping visualization analysis, it was found that the model's attention predominantly focused on nodule regions and effectively captured dynamic associations between clinical data and imaging-derived features. ConclusionThe CGN model, by synergistically combining cross-attention encoding with directed graph-based feature integration, enables effective alignment and fusion of heterogeneous multimodal data. The incorporation of both TCM and western clinical information facilitates complementary feature enrichment, thereby enhancing predictive accuracy for pulmonary nodule progression. This approach holds significant potential for supporting intelligent risk stratification and personalized surveillance strategies in lung cancer prevention.
8.Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.
Lin-Zi LONG ; Ling TAN ; Feng-Qin XU ; Wen-Wen YANG ; Hong-Zheng LI ; Jian-Gang LIU ; Ke WANG ; Zhi-Ru ZHAO ; Yue-Qi WANG ; Chao-Ju WANG ; Yi-Chao WEN ; Ming-Yan HUANG ; Hua QU ; Chang-Geng FU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(5):402-411
OBJECTIVE:
To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved.
METHODS:
Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS:
The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01).
CONCLUSIONS
Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals
;
Drugs, Chinese Herbal/therapeutic use*
;
Hypertension/pathology*
;
Renin-Angiotensin System/drug effects*
;
Rats, Inbred SHR
;
Oxidative Stress/drug effects*
;
Male
;
Rats, Inbred WKY
;
Blood Pressure/drug effects*
;
Myocardium/pathology*
;
Rats
;
Inflammation/pathology*
9.Shexiang Tongxin Dropping Pill Improves Stable Angina Patients with Phlegm-Heat and Blood-Stasis Syndrome: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Ying-Qiang ZHAO ; Yong-Fa XING ; Ke-Yong ZOU ; Wei-Dong JIANG ; Ting-Hai DU ; Bo CHEN ; Bao-Ping YANG ; Bai-Ming QU ; Li-Yue WANG ; Gui-Hong GONG ; Yan-Ling SUN ; Li-Qi WANG ; Gao-Feng ZHOU ; Yu-Gang DONG ; Min CHEN ; Xue-Juan ZHANG ; Tian-Lun YANG ; Min-Zhou ZHANG ; Ming-Jun ZHAO ; Yue DENG ; Chang-Jiang XIAO ; Lin WANG ; Bao-He WANG
Chinese journal of integrative medicine 2025;31(8):685-693
OBJECTIVE:
To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents.
METHODS:
This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs).
RESULTS:
This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed.
CONCLUSION
STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans
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Double-Blind Method
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Drugs, Chinese Herbal/adverse effects*
;
Male
;
Female
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Middle Aged
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Angina, Stable/physiopathology*
;
Aged
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Syndrome
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Treatment Outcome
;
Placebos
;
Tablets
10.CDH17-targeting CAR-NK cells synergize with CD47 blockade for potent suppression of gastrointestinal cancers.
Liuhai ZHENG ; Youbing DING ; Xiaolong XU ; Huifang WANG ; Guangwei SHI ; Yang LI ; Yuanqiao HE ; Yue GONG ; Xiaodong ZHANG ; Jinxi WEI ; Zhiyu DONG ; Jiexuan LI ; Shanchao ZHAO ; Rui HOU ; Wei ZHANG ; Jigang WANG ; Zhijie LI
Acta Pharmaceutica Sinica B 2025;15(5):2559-2574
Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.


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