1.Mechanisms and research progress of circular RNAs in radon exposure-induced diseases
Jia ZHANG ; Xiaoliang LI ; Jianlei RUAN ; Jianxiang LIU
Chinese Journal of Radiological Health 2025;34(2):303-308
Radon, the only naturally occurring radioactive noble gas, is among the most common radioactive nuclides to which humans are exposed. Radon can induce various biological effects in the human body and is a risk factor for lung cancer. Circular RNAs (circRNAs) are stable, tissue-specific, and abundantly expressed in body fluids. circRNAs can regulate gene expression and play an important role in the development of cancer. In this paper, we summarized the changes in the expression and function of circRNAs, highlighting the potential mechanisms of circRNAs in radon exposure-induced cancers. Our results provided theoretical support for the use of circRNAs as a biomarker of radon exposure-induced radiation damage, and offer a theoretical basis for the early diagnosis, treatment, and prevention of radon exposure-induced diseases.
2.Chinese expert consensus on integrated case management by a multidisciplinary team in CAR-T cell therapy for lymphoma.
Sanfang TU ; Ping LI ; Heng MEI ; Yang LIU ; Yongxian HU ; Peng LIU ; Dehui ZOU ; Ting NIU ; Kailin XU ; Li WANG ; Jianmin YANG ; Mingfeng ZHAO ; Xiaojun HUANG ; Jianxiang WANG ; Yu HU ; Weili ZHAO ; Depei WU ; Jun MA ; Wenbin QIAN ; Weidong HAN ; Yuhua LI ; Aibin LIANG
Chinese Medical Journal 2025;138(16):1894-1896
3.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
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Lymphoma, Large B-Cell, Diffuse/therapy*
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Tumor Microenvironment/genetics*
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Antigens, CD19/metabolism*
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Leukemia, Myelomonocytic, Chronic/genetics*
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Immunotherapy, Adoptive/adverse effects*
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Male
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Single-Cell Analysis/methods*
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Female
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Sequence Analysis, RNA/methods*
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Receptors, Chimeric Antigen
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Middle Aged
4.Summary of the academic thoughts of Professor XU Nenggui on the "governor vessel regulating spirit" acupuncture method for post-stroke dysphagia.
Hongtao LI ; Lubao FENG ; Lizhi ZHANG ; Lulu YAO ; Lin WANG ; Xu Nenggui DIRECTOR
Chinese Acupuncture & Moxibustion 2025;45(8):1128-1133
Based on his extensive clinical experience and the team's mechanistic research, Professor XU Nenggui has proposed the academic concept that "the governor vessel governs the brain and treats cerebral viscus diseases", and established a novel acupuncture approach for encephalopathy treatment centered on the integrated theory of "governor vessel-brain-mind", and developed a staged acupuncture protocol of "governor vessel regulating spirit" for ischemic stroke. This article introduces the academic features of this method in treating post-stroke dysphagia from four aspects: theoretical framework, treatment principles and point selection, mechanistic research, and clinical case studies. In clinical application, the method emphasizes syndrome differentiation based on meridians, harmonization between the conception and governor vessels; precise acupoint selection to treat both form and spirit; stage-specific differentiation with targeted needling. Furthermore, Professor XU integrates basic research with clinical practice, focusing on the neurobiological mechanisms underlying the efficacy of acupuncture in treating post-stroke dysphagia.
Acupuncture Therapy/methods*
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Humans
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Deglutition Disorders/psychology*
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Stroke/complications*
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Meridians
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Acupuncture Points
5.Self-illuminating liposome-derived in situ triggerable photodynamic therapy combining radionuclide therapy for synergistic treatment of lung cancer.
Chunsen YUAN ; Taotao JIN ; Hangke LEI ; Juanjuan LIU ; Wendan PU ; Yang ZHANG ; Chenwen LI ; Dingde HUANG ; Jianxiang ZHANG ; Jiawei GUO
Acta Pharmaceutica Sinica B 2025;15(10):4973-4994
The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-177Lu was engineered by incorporating the radionuclide 177Lu into CLL. CLL-177Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-177Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-177Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.
6.Orally deliverable biomimetic nucleic acid therapies for targeted treatment of atherosclerosis.
Chenwen LI ; Yidan CHEN ; Yuan LI ; Huan LIU ; Shengqian YANG ; Yongyao LIN ; Yuantong QI ; Songling HAN ; Yin DOU ; Gaoxing LUO ; Yingxue HAO ; Jianxiang ZHANG
Acta Pharmaceutica Sinica B 2025;15(11):6052-6069
Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE -/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.
7.Effects of occupational radiation exposure on peripheral blood lymphocyte count and cell cycle in logging workers
Weiguo LI ; Gang GAO ; Yan PAN ; Hailiang LI ; Jianlei RUAN ; Chunnan PIAO ; Jinghong FU ; Jianxiang LIU
Chinese Journal of Radiological Health 2024;33(1):28-32
Objective To investigate the effects of prolonged low-dose neutron-γ radiation on peripheral blood lymphocytes of logging workers. Methods The health information of workers in a logging company was collected by on-site blood sample collection and questionnaire survey. Individual doses of γ and neutron radiation were recorded using LiF elements and CR-39, respectively. Lymphocyte count in peripheral blood was measured by blood cytometer. Cell cycle and cyclins were detected by flow cytometry. Results The annual dose of some logging workers exceeded 5 mSv. Lymphocyte counts showed a difference of 15% between the group exposed to the lowest annual dose of 0–1 mSv (mean: 2.45 × 109/L) and the group exposed to the highest annual dose of 5–25 mSv (mean: 2.08 × 109/L). In comparison to pre-shift workers, logging workers exhibited a G1-phase arrest in the lymphocyte cycle, along with increased expression of cyclins p21 and CDK2. Conclusion Prolonged exposure to low-dose neutron-γ radiation leads to reduced lymphocyte counts as well as changes in lymphocyte cycle and cyclin expression.
8.Gene analysis of polymerase basic protein 2 variant strains of influenza virus H1N1pdm09 subtype in Guangdong province
Lijun LIANG ; Qianfang GUO ; Yushi HUANG ; Jianxiang YU ; Lirong ZOU ; Huan ZHANG ; Haiyan WANG ; Zhencui LI ; Baisheng LI
Chinese Journal of Experimental and Clinical Virology 2024;38(5):558-563
Objective:To understand the molecular characteristics of the mutant strain of polymerase basic protein 2 (PB2) gene of influenza A (H1N1pdm) in Guangdong province, and to explore its specific molecular sites, so as to provide scientific basis for the prevention and control of influenza virus.Methods:Throat swab samples were collected from 2 cases infected with PB2 gene variant strains for virus isolation, and 23 influenza virus strains were selected from Guangdong province for sequencing analysis. The reference sequences and vaccine strain sequences provided by GISAID were used to perform evolutionary analysis on hemagglutinin (HA) and PB2 genes. Virus strain antigen analysis and neuraminidase (NA) inhibition test were carried out. PB2 protein model was constructed and polymerase activity was analyzed.Results:H399N amino acid mutation occurred in the HA gene of PB2-D701N and PB2-A271S variant strains, both of which belonged to the branch of 6B.1A.5a.2a. They belonged to the same big branch and different small branches as the vaccine strain A/Victoria/4897/2022, and they are all vaccine-like strains. In the three-dimensional structure, the mutations of PB2-D701N and PB2-A271S change charge and hydrophobicity.Conclusions:PB2-D701 and A271 were highly conserved, and PB2 mutant strains were not the dominant strains. The PB2 mutant had high antigenicity with the vaccine. The PB2 mutant strain is sensitive to NA inhibitors. The three-dimensional model predicted that PB2-D701N mutation could enhance virulence and affect transmissibility of influenza virus, while PB2-A271S mutation could affect polymerase activity and polymerase complex synthesis of influenza virus.
9.Analysis of current status of lipid-lowering therapy and factors associated with low-density lipoprotein cholesterol goal attainment in patients with coronary heart disease combined with hypertension
Zekun FENG ; Chi WANG ; Lu TIAN ; Yanjie LI ; Lihua LAN ; Jianxiang HUANG ; Zhen GE ; Hao XUE ; Qian XIN
Chinese Journal of General Practitioners 2024;23(6):625-632
Objective:To explore the current status of lipid-lowering therapy, the distribution of low-density lipoprotein cholesterol (LDL-C) levels and the risk assessment of cardiovascular events recurrence in patients with coronary heart disease (CHD) complicated by hypertension.Methods:This was a cross-sectional study. Patients with CHD combined with hypertension were hospitalized in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from August 5, 2008 to July 22, 2018 were included, and were divided into standard group and substandard group according to whether LDL-C reached the standard. Study data were obtained from inpatient coronary angiography records and electronic medical records database of Department of Cardiology, General Hospital of Chinese People′s Liberation Army, who used data from the first diagnosis of CHD. Clinical data of the selected patients were collected. Multivariate logistic regression model was used to analyze the associated factors of whether LDL-C reached the standard in CHD patients with hypertension.Results:A total of 18 800 patients were selected from 31 provinces/autonomous regions/municipalities directly under the central government in China, with Beijing accounting for the largest proportion (5 692 patients (30.28%)), followed by Hebei (3 621 patients (19.26%)), Henan (1 837 patients (9.77%)), and Shandong (1 618 patients (8.61%)). Among the selected patients, 1 493 had LDL-C<1.4 mmol/L (standard group), and 17 307 had LDL-C≥1.4 mmol/L (substandard group). Only 1 493 patients (7.94%) had LDL-C<1.4 mmol/L. There were 4 518 patients (24.03%), 4 366 patients (23.22%), 6 924 patients (36.83%) and 1 499 patients (7.97%) with LDL-C for 1.4-<2.0, 2.0-<2.5, 2.5-<3.8 and≥3.8 mmol/L levels, respectively. 17 855 patients (95.15%) were treated with statins, but only 1 334 patients (7.10%) were treated with statins and ezetimibe. Of the selected patients, 4 986 patients (26.52%) were at low risk, 6 515 patients (34.65%) were at intermediate risk, and 7 299 patients (38.82%) were at high risk. The combined lipid-lowering treatment rates of statin and ezetimibe in the middle-and high-risk patients were 7.43% (484/6 515) and 7.48% (546/7 299), respectively. The results of multivariate logistic regression analysis showed that increasing age, male, diabetes mellitus, stroke, and history of percutaneous coronary intervention (PCI) were positively associated with LDL-C standards in patients with CHD and hypertension, whereas obesity and acute myocardial infarction (AMI) were negatively associated with LDL-C standards (all P<0.01). Conclusions:The rate of achieving the standard LDL-C in patients with CHD combined with hypertension was low in China. Although the majority of patients had received moderate-intensity statin therapy, the proportion of statin-treated patients combined with ezetimibe was extremely low. The proportion of high-risk patients with recurrent cardiovascular events was higher in patients with CHD and hypertension in China, whereas the proportion of such patients receiving statin combined with ezetimibe lipid-lowering therapy was lower. This study also found that increasing age, male, diabetes mellitus, stroke, and history of PCI were positively associated with LDL-C standards, while obesity and AMI were negatively associated with LDL-C standards in patients with CHD and hypertension.
10.Effects of continuing nursing model based on "Internet+" in premature infants
Ying LI ; Jianxiang CHEN ; Xiaofei SHI
Chinese Journal of Modern Nursing 2024;30(18):2446-2451
Objective:To explore the effects of the continuing nursing model based on "Internet +" in premature infants and their families.Methods:Premature infants and their families admitted to the Department of Neonatology, Wenzhou Central Hospital, from July 2021 to October 2022 were selected by convenience sampling. They were randomly divided into control group and observation group, each consisting of 108 pairs. Infants in the control group received routine nursing intervention, while those in the observation group received "Internet +" based continuing nursing based on the care provided to the control group. Physical growth indicators (weight, length, head circumference), Neonatal Behavioral Neurological Assessment (NBNA) scores, family caregiving knowledge and ability scores were measured before intervention (at birth) and after intervention (at 6 months of age) in both groups. The occurrence of delayed physical development and unplanned rehospitalization of premature infants at 6 months of age was also recorded.Results:After intervention, the physical growth indicators, NBNA scores, and family caregiving knowledge and ability scores of both groups improved, with the observation group higher than the control group, and the differences were statistically significant (all P<0.05). At 6 months of age, the observation group had lower rates of delayed physical development and unplanned rehospitalization compared to the control group, with statistically significant differences (all P<0.05) . Conclusions:The continuing nursing model based on "Internet +" can effectively improve the caregiving knowledge and ability of premature infants' families, promote the growth and development of premature infants, and reduce the risk of delayed physical development and rehospitalization.

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