1.Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing.
Xudong LI ; Hong HUANG ; Fang WANG ; Mengjia LI ; Binglei ZHANG ; Jianxiang SHI ; Yuke LIU ; Mengya GAO ; Mingxia SUN ; Haixia CAO ; Danfeng ZHANG ; Na SHEN ; Weijie CAO ; Zhilei BIAN ; Haizhou XING ; Wei LI ; Linping XU ; Shiyu ZUO ; Yongping SONG
Chinese Medical Journal 2025;138(15):1866-1881
BACKGROUND:
Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets.
METHODS:
In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis.
RESULTS:
In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment.
CONCLUSIONS
This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans
;
Lymphoma, Large B-Cell, Diffuse/therapy*
;
Tumor Microenvironment/genetics*
;
Antigens, CD19/metabolism*
;
Leukemia, Myelomonocytic, Chronic/genetics*
;
Immunotherapy, Adoptive/adverse effects*
;
Male
;
Single-Cell Analysis/methods*
;
Female
;
Sequence Analysis, RNA/methods*
;
Receptors, Chimeric Antigen
;
Middle Aged
3.Expert Consensus on Perioperative Nursing Care for Follicular Unit Extraction(2025)
Chunhua ZHANG ; Weiwei BIAN ; Congmin WANG ; Lin SHEN ; Yong MIAO ; Na LIU ; Shan JIA ; Junhong AN ; Hongxia WANG ; Dongmei ZHANG
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1606-1613
To promote the standardization and normalization of perioperative care for follicular unit extraction(FUE) hair transplantation, ensure treatment efficacy, and align with advancements in the specialty, the Nursing Branch of the Chinese Association of Plastic and Aesthetics organized a panel of domestic experts. By integrating evidence-based medicine with clinical practice experience, and following thorough discussions, these experts developed the Clinical Practice
4.Re-understanding of the mechanism of coagulation disorder in liver cirrhosis
Rongrong SUN ; Na HE ; Fenna ZHANG ; Xinyi ZHANG ; Ziyi WANG ; Hui WANG ; Nana BIAN ; Honglin YAN
Journal of Clinical Hepatology 2024;40(3):616-620
The liver plays an important regulatory role in maintaining the dynamic balance of coagulation and anticoagulation in the body. Such dynamic balance is fragile in patients with liver cirrhosis, and the risk of bleeding can be increased due to reductions in coagulation factors and platelet count and excessive fibrinolysis; meanwhile, thrombus can be formed due to the increases in von Willebrand factor and coagulation factor Ⅷ, the reductions in anticoagulant protein C and anticoagulant protein S, the increase in thrombin-generating potential, and alterations in antifibrinolytic components. This article reviews the mechanisms of coagulation disorder in liver cirrhosis, so as to help clinicians with the prevention and treatment of bleeding or thrombotic disorders in patients with liver cirrhosis.
5.On the practice form of medical humanities
Chinese Medical Ethics 2024;37(7):852-859
The practice form of medical humanities has the most fundamental significance among many forms of medical humanities.The value of medical humanities can only be truly realized and exert a practical impact across different levels and areas of healthcare when other forms are ultimately transformed into practical processes and achieve practical results.Clinical practice is the main venue for the practice of medical humanities,and the doctor-patient relationship is the primary field where medical humanities exert their influence.In the fields of social health care system construction,medical education and its reform,medical humanities can really play a role through its practice form and operation process.It is the essence of medical humanities that practice forms play a role effectively.The effective role of practice is the essential prescriptive nature of medical humanities.
6.The concept of family ethics is indispensable in psychiatric ethics:a review of the viewpoint of"psychiatric ethics"in book Contemporary Medicine and Confucian Thought
Chinese Medical Ethics 2024;37(12):1406-1411
Psychiatric ethics is a component of Fan Ruiping's book Contemporary Medicine and Confucian Thought with unique academic perspectives.Fan Ruiping stood from the Confucian bioethical standpoint,analyzing and criticizing the medical individualism stance reflected in Article 30 of the Mental Health Law.of People's Republic of china on the voluntariness principle of in-patient therapy for mental disorders.Based on the comparison of cognitive paths and practical methods of bioethics in Eastern and Western,through in-depth analysis of multiple cases,he reflected on how Confucian psychiatric ethics should develop in the contemporary era and the necessity of improving Confucian family-oriented ethical practices.With the help of Fan Ruiping's cognitive conclusions,this paper questioned the moral basis of Article 30 of the Mental Health Law,discussed the special ethical regulations of the"autonomy"of patients with mental disorders,and advised Fan Ruiping's on the multifaceted issues confronting Confucian family ethics in response to international psychiatric ethics.
7.Factors associated with depression after mild acute ischaemic stroke in the elderly and their predictive value
Yongming ZOU ; Rui SHU ; Na WANG ; Ji BIAN ; Lingya QIAO ; Xiaolin XU
Chinese Journal of Geriatrics 2024;43(3):291-296
Objective:To examine the risk factors and predictive value of depression following mild acute ischemic stroke in elderly individuals.The aim is to enhance early identification and intervention, ultimately leading to improved prognosis.Methods:A case-control study was conducted on 988 elderly patients with mild acute ischemic stroke.The study collected general population and social data, as well as clinical laboratory data such as blood glucose, blood lipids, and AD7C-NTP in urine.Additionally, the patients underwent assessments using the Montreal Cognitive Assessment Scale(MoCA), National Institutes of Health Stroke Scale(NHISS), Barthel index(BI), Hamilton Anxiety Scale(HAMA), and Hamilton Depression Scale(HAMD).Based on the HAMD depression scale score, the patients were divided into a nopost-stooke depression(NPSD)group and a post-stooke depression(PSD)group.The study then analyzed the related risk factors and predictive value of PSD.Results:A total of 988 patients were eligible for inclusion, with 132 being excluded and 856 being included.The NPSD and PSD groups showed significant differences in age, hypertension, smoking history, education level, and stroke history(all P<0.05).Regarding clinical data, there were statistically significant differences between the two groups in total cholesterol(TC), triacylglycerol(TG), HDL, urinary AD7C-NTP, MoCA, and HAMA scores(all P<0.05).The results of the multi-factor logistic regression analysis revealed that gender( OR=1.975, 95% CI: 1.223-3.190, P=0.005), stroke history( OR=1.352, 95% CI: 0.877-2.086, P=0.042), and HAMA score( OR=1.216, 95% CI: 0.932-1.526, P=0.043)were identified as independent risk factors for post-stroke depression in the elderly.Conversely, MoCA score( OR=0.873, 95% CI: 0.814-0.937, P<0.001)was found to be an independent protective factor.Furthermore, the ROC curve analysis demonstrated that the HAMA score(AUC=0.892, sensitivity: 0.721, specificity: 0.854, cut-off value: 9.5)exhibited significant predictive value, while the other indexes had limited predictive value. Conclusions:Gender, stroke history, and HAMA score have been identified as potential independent risk factors for post-stroke depression(PSD)in the elderly, while MoCA score may serve as an independent protective factor.Notably, HAMA score demonstrates a strong predictive ability for PSD.Early identification of these factors and timely intervention could significantly contribute to improving prognosis.
8.Expression of SMOC1 and OLFML3 in Cerebrospinal Fluid of Patients with Alzheimer's Disease and Its Value in Evaluating the Severity of the Disease
Qian LIU ; Na BIAN ; Yangyuan SUN
Journal of Modern Laboratory Medicine 2024;39(6):124-129
Objective To explore the expression levels of SPARC related modular calcium binding 1(SMOC1)and olfactomedin-3(OLFM3)in the cerebrospinal fluid of Alzheimer's disease(AD)patients and their value in evaluating the severity of the disease.Methods A total of 108 AD patients(AD group)treated at Baoji People's Hospital from January 2020 to January 2023 were selected,and 60 non cognitive dysfunction patients who underwent lumbar puncture examination during the same period were selected as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect cerebrospinal fluid SMOC1,OLFML3,β-Amyloid protein(Aβ1-40,Aβ1-42)and P-Tau protein levels.Pearson correlation analysis was conducted to analyze cerebrospinal fluid SMOC1,and OLFML3 levels and their correlation with clinical indicators.Logistic regression was used to analyze the influencing factors of AD severity.Receiver operating characteristic curves were used to analyze the predictive value of cerebrospinal fluid SMOC1 and OLFML3 on the severity of Alzheimer's disease.Results The levels of SMOC1(68.47±11.23 ng/L),OLFML3(110.58±21.39 ng/L),P-Tau(569.07±97.24 ng/L)and CDR score(1.5 score)in the cerebrospinal fluid of the AD group were higher than those in the control group(22.60±4.16 ng/L,36.94±6.97ng/L,182.66±55.37,0 score),while Aβ1-42(292.23±55.36 ng/L),MoCA score(7.88±2.05 score)and MMSE score(13.15±2.39 score)were lower than those in the control group(397.16±60.57ng/L,23.13±4.31 score,28.02±4.26 score),and the differences were statistically significant(t=30.465,25.885,28.313,51.211,11.380,31.038,29.013,all P<0.05).SMOC1 and OLFML3 of the cerebrospinal fluid in the AD group were positively correlated with P-Tau and CDR score(r=0.703,0.634;0.682,0.713,all P<0.05),but were negatively correlated with Aβ1-42,MoCA score and MMSE score(r=-0.662,-0.599;-0.660,-0.588;-0.745,-0.731,all P<0.05).SMOC1(89.90±12.17 ng/L),OLFML3(142.46±22.48),and P-Tau(618.83±98.19 ng/L)in the cerebrospinal fluid of AD patients in the moderate to severe group were higher than those in the mild group(56.36±10.52 ng/L,92.56±20.25 ng/L,542.25±95.30 ng/L),Aβ1-42 in the moderate to severe group(260.76±53.60 ng/L)was lower than those in the mild group(310.02±56.54 ng/L),and the differences were statistically significant(t=15.029,11.818,3.968,4.430,all P<0.05).SMOC1(OR=1.451,95%CI:1.120~1.879),OLFML3(OR=1.442,95%CI:1.096~1.897)and P-Tau(OR=1.589,95%CI:1.258~2.006)in cerebrospinal fluid were risk factors for moderate to severe cognitive impairment in AD patients,while Aβ1-42 was a protective factor.The AUC(95%CI)of SMOC1,OLFML3 in cerebrospinal fluid,and their combinative forecasting evaluating moderate to severe AD patients were 0.882(0.844~0.929),0.846(0.805~0.877)and 0.931(0.883~0.965),respectively,and their combinative forecasting was higher than two individual indicators(Z=3.558,4.172,P=0.004,0.000).Conclusion The levels of SMOC1 and OLFML3 in cerebrospinal fluid are elevated in AD patients,which are related to the severity of AD.The combinative forecasting of the two has high predictive value for moderate to severe AD.
9.Effect of QCC activity management on emergency PCI time,cardiac function and prognosis in AMI pa-tients
Na WANG ; Chun-Yun BIAN ; Xin-Ke ZHANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(3):280-284
Objective:To investigate the effect of quality control circle(QCC)activity management on operation time,cardiac function and prognosis in patients with acute myocardial infarction(AMI)undergoing percutaneous coronary intervention(PCI).Methods:A total of 148 AMI patients who admitted to the emergency department of our hospital and underwent PCI from January to June 2021 were selected.According to different hospital manage-ment patterns,patients were divided into control group(n=74)and QCC group(n=74).Emergency detention time,PCI time,cardiac function indexes at 7d and 14d after PCI,patient satisfaction and incidence of adverse car-diovascular events on six months after PCI were compared between two groups.Results:Compared with control group,there were significant reductions in ECG monitoring time[(11.35±2.13)min vs.(9.14±1.86)min],condition evaluation time[(14.78±2.51)min vs.(10.12±2.28)min],drug preparation time[(29.69±5.03)min vs.(22.65±4.52)min]and PCI time[(83.47±10.76)min vs.(62.18±10.03)min]in QCC group,P=0.001 all.Compared with control group on 14d after PCI,there was significant rise in left ventricular ejection frac-tion(LVEF)[(46.42±2.52)%vs.(58.54±1.82)%],and significant reductions in left ventricular end-systolic volume index(LVESVI)[(33.05±3.47)ml/m2 vs.(28.22±2.49)ml/m2]and left ventricular end-diastolic volume index(LVEDVI)[(69.08±4.53)ml/m2 vs.(56.85±2.48)ml/m2]in QCC group,P<0.01 all.Total satisfaction of QCC group was significantly higher than that of control group(93.24%vs.62.16%),and incidence rate of adverse cardiovascular events on six months after PCI was significantly lower than that of control group(12.16%vs.36.49%),P=0.001 both.Conclusion:QCC activity management intervention can optimize clinical PCI procedure,significantly shorten emergency detention time,operation time,improve cardiac function,reduce postoperative incidence rate of cardiovascular adverse events.It possesses high satisfaction and is worthy of clinical promotion and application.
10.Correlation between CT-based arterial radiomics score and the neo-adjuvant treatment response of pancreatic cancer
Mengmeng ZHU ; Yun BIAN ; Chengwei CHEN ; Jian ZHOU ; Na LI ; Yifei GUO ; Ying LI ; Xiaohan YUAN ; Jieyu YU ; Jianping LU
Chinese Journal of Pancreatology 2024;24(3):190-197
Objective:To identify the relationship between the CT arterial radiomics score and the treatment response to neoadjuvant therapy for pancreatic cancer.Methods:The clinical data of 243 pancreatic cancer patients who received surgical resection after neo-adjuvant therapy in the First Affiliated Hospital of Naval Medical University from March 2017 to March 2023 were retrospectively analyzed. Based on the tumor regression grade (TRG), the patients were divided into good response group (TRG 0-1, n=30) and non-good response group (TRG 2-3, n=213). The clinical, radiological and pathological features were compared between two groups. Fully-automated segmentation tool was used for segmenting the arterial CT scan of pancreatic tumor before and after treatment. Python package was applied to extract the radiomics features of tumors after segmentation and the extracted features were reduced and chosen using the least absolute shrinkage and selection operator (Lasso) logistic regression algorithm. Lasso logistic regression formula was applied to calculate the arterial radiomics score. Univariate and multivariate logistic regression models were used to analyze the association between arterial radiomics score and treatment response to neoadjucant therapy. Receiver operating-characteristics (ROC) curve was drawn and area under curve (AUC), specificity, sensitivity and accuracy for evaluating the treatment response were calculated. The clinical usefulness of arterial radiomics score for diagnosing the response of neoadjuvant treatment for pancreatic cancer were determined by decision curve analysis (DCA) . Results:A total of 330 arterial radiomics CT features were obtained, and 9-selected arterial phase features associated with treatment response were determined after being reduced by the Lasso logistic regression algorithm. Univariate analysis showed that the arterial radiomics score, three-dimensional diameter after neoadjuvant therapy, pancreatic contour, T stage, N stage, Peri-pancreatic nerve invasion, lymph-vascular space invasion (LVSI) and invasion of duodenum were all associated with treatment response (all P value <0.05). Multivariate logistic regression analyses confirmed that arterial radiomics score was obviously associated with the neoadjuvant treatment response ( P<0.001). At the cut-off value of 1.93, AUC of the arterial radiomics score for diagnosing neoadjuvant treatment response was 0.92, and the specificity, sensitivity and accuracy was 86.7%, 84.5% and 84.8%. DCA demonstrated that when the percentage for predicting the treatment response by using the arterial radiomics score was >0.2, the patients could benefit from the application of arterial radiomics score for evaluating neoadjuvant therapy response. Conclusions:The arterial radiomics score was strongly correlated with the neoadjuvant treatment response of pancreatic cancer, and can accurately predict neoadjuant treatment efficacy.

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