1.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*
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Male
;
Female
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Immunotherapy
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Middle Aged
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Aged
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Tumor Microenvironment/immunology*
;
Retrospective Studies
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Microsatellite Instability
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Transcriptome
;
Single-Cell Analysis
;
Programmed Cell Death 1 Receptor/immunology*
;
Gene Expression Profiling
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Adult
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Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*
2.Impact of body habitus and gender on radiation dose in low-dose chest CT with spectral purification technology
Xinnan SHEN ; Xinyou LI ; Gang PENG ; Chengxin WAN ; Yajing YANG ; Zhiwei ZHANG
Chinese Journal of Radiology 2025;59(7):784-790
Objective:To investigate the effects of body habitus and gender on radiation dose assessment methodologies in low-dose chest CT, with particular emphasis on clarifying discrepancies among various dose quantification approaches and their associations with patient characteristics.Methods:Imaging data from 19 371 patients who underwent low-dose chest CT at the First Affiliated Hospital of Chongqing Medical University between January 2021 and January 2024 were retrospectively analyzed. Patients were categorized into eight groups based on water-equivalent diameter (WED) and gender: Group A (150 mm≤WED<210 mm; 71 males, 1 032 females), Group B (210 mm≤WED<260 mm; 4 525 males, 8 005 females), Group C (260 mm≤WED<300 mm; 4 234 males, 1 105 females), and Group D (WED≥300 mm; 357 males, 42 females). WED, size-specific dose estimate (SSDE), and organ dose-based effective dose(ED Radimetrics)were calculated using Radimetrics software. Scanner-reported dose metrics, including volume CT dose index (CTDIvol), dose-length product (DLP), and DLP-derived effective dose(ED DLP), were recorded. The ratios of SSDE/CTDIvol and ED Radimetrics/ED DLP were used to quantify discrepancies between dose evaluation methods. The Kruskal-Wallis test was employed to analyze dose metric differences across WED groups within the same gender, while the Wilcoxon rank-sum test compared gender-based differences within each WED group. Results:All dose metrics significantly increased with WED for both genders (all P<0.05). Within the same WED group, ED Radimetrics was significantly higher in females ( P<0.05), whereas ED DLP was higher in males ( P<0.05). The SSDE/CTDIvol ratio decreased with increasing WED, declining from 1.74 in Group A to 1.16 in Group D for females and from 1.68 to 1.12 for males. The ED Radimetrics/ED DLP ratio exhibited a decreasing trend with WED in females (1.82 to 1.30) but showed an initial increase in males (1.29 in Group A to 1.31 in Group B) before decreasing to 0.94 in Group D (all intergroup P<0.05). SSDE/CTDIvol and ED Radimetrics/ED DLP ratios of females were consistently higher than that of males within each WED group (all P<0.05). Conclusions:Patient body habitus and gender significantly influence radiation dose distribution in low-dose chest CT. Larger body habitus is associated with higher radiation doses, while females receive greater ED Radimetrics than males within comparable body habitus. Traditional dose metrics (CTDIvol and ED DLP) were underestimated for patients with small body sizes and female individuals.
3.Study on the ADC value of deep gray matter nuclei in patients with Parkinson's disease by RESOLVE DWI
Lishu ZHU ; Xinyou LI ; Bin YU ; Yunfeng LU ; Zhiwei ZHANG ; Yongmei LI ; Fajin LYU ; Silin DU
Chongqing Medicine 2025;54(4):915-920
Objective Readout segmentation of long variable echo-trains diffusion weighted imaging(RESOLVE DWI)was used to analyze the difference of apparent diffusion coefficient(ADC)value in deep cerebral nucleus and its correlation with clinical characteristics in patients with Parkinson's disease(PD).Methods Clinical data of 60 patients with PD were retrospectively analyzed as PD group,and were divided in-to the tremor group(n=30)and the bradykinesia group(n=30)according to symptom type,middle-aged(≤65 years old)group(n=23)and elderly(>65 years old)group(n=37)according to age,and 60 healthy vol-unteers were selected as the control group during the same period.ADC values were measured on the ADC map of RESOLVE DWI sequence,and the ADC values of bilateral putamen,pallidus,substantia nigra,rubra,and dentate nucleus were analyzed and their correlation with UPDRS-Ⅲ score and H&Y grading.Results Compared with the control group,the ADC values of both putamen,globus pallidus,globus pallidus,red nucleus,right substantia nigra and right dentate nucleus were increased in the PD group,the ADC values of both putamen,globus pallidus,red nucleus and right substantia nigra in the tremor group were increased,and the ADC values of right putamen,globus pallidus and bilateral red nucleus in the bradykinesia group were increased(P<0.05).Compared with the bradykinesia group,the values of ADC in the tremor group were similar.Compared with the middle-aged group,the ADC values of right putamen,bilateral globus pallidus,left substantia nigra and left red nucleus were higher in the elderly group(P<0.05).In the PD group,the ADC values of the right putamen,globus pallidus,and dentate nucleus were positively correlated with H&Y grade and UPDRS-Ⅲscore,and the ADC value of the left putamen was positively correlated with H&Y grade.Conclusion RE-SOLVE DWI can be used to evaluate the differences in deep gray matter nuclei in PD patients,and its ADC value may be used to evaluate and predict the severity of nuclear mass damage and motor symptoms in PD pa-tients.
4.Research status and development trends of medical image recognition technology
Shili WU ; Yongkun GUO ; Chao QIAN ; Ying LI ; Xinyou ZHANG
Chinese Journal of Medical Physics 2025;42(6):719-729
Medical image recognition is a technology that utilizes computer algorithms to process,analyze and understand medical images,aiming to identify various patterns,targets and objects,thereby aiding doctors in more accurate diagnosis and treatment.Current researches in medical image recognition mainly focuses on medical image classification,lesion location and segmentation,image registration and fusion,content-based image retrieval,as well as three-dimensional reconstruction and visualization.The review provides a summary of the research directions and trends in medical image recognition,introducing concepts and technologies such as deep learning,multimodal fusion,three-dimensional reconstruction and visualization.It also highlights the applications of medical image recognition in medical imaging diagnosis,pathological analysis and radiotherapy planning,while pointing out the existing problems and challenges.Furthermore,the future developments and challenges of medical image recognition technology are put forward for providing a reference for medical image recognition research and clinical medical image analysis.
5.Research status and development trends of medical image recognition technology
Shili WU ; Yongkun GUO ; Chao QIAN ; Ying LI ; Xinyou ZHANG
Chinese Journal of Medical Physics 2025;42(6):719-729
Medical image recognition is a technology that utilizes computer algorithms to process,analyze and understand medical images,aiming to identify various patterns,targets and objects,thereby aiding doctors in more accurate diagnosis and treatment.Current researches in medical image recognition mainly focuses on medical image classification,lesion location and segmentation,image registration and fusion,content-based image retrieval,as well as three-dimensional reconstruction and visualization.The review provides a summary of the research directions and trends in medical image recognition,introducing concepts and technologies such as deep learning,multimodal fusion,three-dimensional reconstruction and visualization.It also highlights the applications of medical image recognition in medical imaging diagnosis,pathological analysis and radiotherapy planning,while pointing out the existing problems and challenges.Furthermore,the future developments and challenges of medical image recognition technology are put forward for providing a reference for medical image recognition research and clinical medical image analysis.
6.Impact of body habitus and gender on radiation dose in low-dose chest CT with spectral purification technology
Xinnan SHEN ; Xinyou LI ; Gang PENG ; Chengxin WAN ; Yajing YANG ; Zhiwei ZHANG
Chinese Journal of Radiology 2025;59(7):784-790
Objective:To investigate the effects of body habitus and gender on radiation dose assessment methodologies in low-dose chest CT, with particular emphasis on clarifying discrepancies among various dose quantification approaches and their associations with patient characteristics.Methods:Imaging data from 19 371 patients who underwent low-dose chest CT at the First Affiliated Hospital of Chongqing Medical University between January 2021 and January 2024 were retrospectively analyzed. Patients were categorized into eight groups based on water-equivalent diameter (WED) and gender: Group A (150 mm≤WED<210 mm; 71 males, 1 032 females), Group B (210 mm≤WED<260 mm; 4 525 males, 8 005 females), Group C (260 mm≤WED<300 mm; 4 234 males, 1 105 females), and Group D (WED≥300 mm; 357 males, 42 females). WED, size-specific dose estimate (SSDE), and organ dose-based effective dose(ED Radimetrics)were calculated using Radimetrics software. Scanner-reported dose metrics, including volume CT dose index (CTDIvol), dose-length product (DLP), and DLP-derived effective dose(ED DLP), were recorded. The ratios of SSDE/CTDIvol and ED Radimetrics/ED DLP were used to quantify discrepancies between dose evaluation methods. The Kruskal-Wallis test was employed to analyze dose metric differences across WED groups within the same gender, while the Wilcoxon rank-sum test compared gender-based differences within each WED group. Results:All dose metrics significantly increased with WED for both genders (all P<0.05). Within the same WED group, ED Radimetrics was significantly higher in females ( P<0.05), whereas ED DLP was higher in males ( P<0.05). The SSDE/CTDIvol ratio decreased with increasing WED, declining from 1.74 in Group A to 1.16 in Group D for females and from 1.68 to 1.12 for males. The ED Radimetrics/ED DLP ratio exhibited a decreasing trend with WED in females (1.82 to 1.30) but showed an initial increase in males (1.29 in Group A to 1.31 in Group B) before decreasing to 0.94 in Group D (all intergroup P<0.05). SSDE/CTDIvol and ED Radimetrics/ED DLP ratios of females were consistently higher than that of males within each WED group (all P<0.05). Conclusions:Patient body habitus and gender significantly influence radiation dose distribution in low-dose chest CT. Larger body habitus is associated with higher radiation doses, while females receive greater ED Radimetrics than males within comparable body habitus. Traditional dose metrics (CTDIvol and ED DLP) were underestimated for patients with small body sizes and female individuals.
7.Application value of flow cytometry in chronic disease assessment
Chinese Journal of Laboratory Medicine 2024;47(7):713-716
Flow cytometry (FCM) is a technique that can perform the multiparametric analysis of single cell. Recently, FCM has become an important tool to assist the management of chronic diseases. The clinical application of FCM has expanded from blood diseases such as leukemia and lymphoma to other chronic diseases such as solid tumors and chronic obstructive lung. Besides, FCM plays an important role in improving the efficacy of early diagnosis, monitoring on the immune status of patients, understanding of the disease progression, and assessment of prognosis of patients. Henceforth, more assistance could be provided by FCM to optimize the management of chronic diseases with the continuous innovation.
8.Clinical application progress of flow cytometry in diagnosis and therapeutic monitoring of patients with nonhematopoietic neoplasms
Qianwen HU ; Suwen YANG ; Sai QIAO ; Xinyou XIE ; Jun ZHANG
Chinese Journal of Laboratory Medicine 2024;47(7):722-728
Flow cytometry (FCM) is an interdisciplinary cell analysis technology that integrates optics, fluid dynamics, electronics, and computer science. While FCM is widely utilized in diagnosing and monitoring hematologic malignancies, its application in nonhematopoietic neoplasms (NHN) remains in its nascent stages. However, recent advancements in science and technology have led to the emergence of innovative FCM technologies, such as mass spectrometry flow cytometry (CyTOF) and spectral flow cytometry (SFC), offering promising avenues for their clinical application aiming to assist the clinical diagnosis of NHN patients. This review summarizes the features of fundamentals of traditional FCM, CyTOF, and SFC technologies, along with their applications and future prospective in NHN diagnosis and treatment, aiming to offer updated insights for the continued expansion and utilization of FCM technology in clinical laboratory settings.
9.Efficacy and safety of bcl-2 inhibitor venetoclax combined with hypomethylating agents in treatment of myeloid neoplasms
Journal of Leukemia & Lymphoma 2024;33(12):719-725
Objective:To explore the efficacy and adverse reactions of bcl-2 inhibitor venetoclax (VEN) combined with hypomethylating agents (HMA) in treatment of adult myeloid neoplasms.Methods:A retrospective case series study was conducted. The clinical data of 43 patients with myeloid neoplasms treated by VEN combined with HMA in Shenzhen People's Hospital between December 2018 and December 2022 were collected. The general data, short-term efficacy, survival and adverse reactions of patients were summarized.Results:A total of 43 patients were enrolled in the study, of which 24 cases (55.8%) were male with the mean age [ M ( Q1, Q3)] of 64 years (55 years, 69 years). All 43 patients included 28 cases (65.1%) of acute myeloid leukemia (AML), 14 cases (32.6%) of high-risk myelodysplastic syndrome (HR-MDS) and 1 case (2.3%) of chronic myelomonocytic leukemia. The overall response rate (ORR) was 83.7%(36/43); the rate of complete remission (CR) / incomplete blood count recovery (CRi) or marrow complete remission (mCR) rate was 72.1% (31/43); and the negative rate of minimal residual disease (MRD) of patients achieving CR/CRi or mCR was 45.2% (14/31). The ORR of AML and HR-MDS patients was 89.3% (25/28), 71.4% (10/14), respectively; the CR/CRi or mCR rate of AML and HR-MDS patients was 75.0% (21/28) and 64.3% (9/14), respectively. The negative rate of MRD of patients achieving CR/CRi or mCR was 47.6% (10/21), 44.4% (4/9); there were no statistically significant differences in ORR, CR/CRi or mCR rates and the MRD negative rates among patients achieving CR/CRi or mCR (all P > 0.05). The median follow-up time was 30.0 months (range: 1.0-41.0 months). The median progress-free survival (PFS) and the overall survival (OS) time of all groups was 8.0 months, 15.0 months, respectively. The median PFS time was 8.5 months and 7.0 months, respectively in AML and HR-MDS patients, and the difference in PFS was statistically significant ( P = 0.154); the median OS time was 24.0 months and 10.0 months, respectively in AML and HR-MDS patients, and the difference in OS was statistically significant ( P = 0.020). The median OS was not reached in 12 patients who bridged to allogeneic hematopoietic stem cell transplantation and the median OS time was 15.0 months in 13 patients who did not undergo the transplantation; and the difference in OS between the transplantation group and non-transplantation group was statistically significant ( P = 0.008). Grade 3-4 myelosuppression occurred in 97.7% patients (42/43) in all groups and grade 3-4 agranulocytosis combined with fever occurred in 48.8% patients (21/43). In all groups, 6 patients (14.0%) developed grade 3-4 infection during treatment, and 3 HR-MDS patients of them died due to severe infection during treatment. All the non-hematological adverse reactions were grade 1-2. Conclusions:VEN+HMA regimen shows good therapeutic effects in myeloid neoplasms patients, with rapid deep remission. The prolonged survival time can be achieved in some patients who successfully bridged to allogeneic hematopoietic stem cell transplantation. The survival benefit in AML patients may be better than that in HR-MDS patients. Most myeloid neoplasms patients still suffer the different degrees of bone marrow suppression during treatment with VEN+HMA.
10.Diagnosis and treatment progress of liver injury after allogeneic hematopoietic stem cell transplantation
Jingsong WU ; Xinyou ZHANG ; Jihao ZHOU
Journal of Leukemia & Lymphoma 2024;33(3):189-192
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative method for various hematological diseases. With the optimization of transplantation technology, the clinical application of allo-HSCT is more and more mature. Post-transplant liver injury is one of the common postoperative complications, which seriously affects the quality of life and long-term survival of patients. The causes of liver injury after allo-HSCT can be divided into non-infectious and infectious factors, which show similar clinical manifestations and different treatment principles. Timely diagnosis of post-transplant liver injury and the identification of the disease cause will be beneficial for early prevention or targeted treatment, thereby improving patients' prognosis. This review focuses on the etiology, clinical features, and treatment options of liver injury after allo-HSCT, aiming to deepen the understanding of hematologists on liver injury after allo-HSCT.

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