1.Advances in research on fine motion control of prosthesis fingers with brain-computer interface
Di GAN ; Hui HUANG ; Chengzhi LI ; Shiyu ZHANG ; Shiyuan WANG ; Tao WANG
Chinese Journal of Clinical Medicine 2025;32(1):114-119
The deficiency of fingers due to various reasons leads to a certain degree of loss of full or part hand functions. Physical and mental health of patients are seriously affected, and patients have varying degrees of reduced quality of life. Prosthesis fingers play an important role in completing the body shape and enhancing patients’ self-confidence and self-esteem. However, how to make prosthesis fingers perform coordinated movements and restore complete functions is a crucial problem that urgently needs to be solved. This paper reviews the methods of brain-computer interface controlled fine finger movements and elaborates on the origin, current situation, and advancements of the development of this technology, laying a foundation for subsequent research, with the expectation of helping patients solve the problems arising from the insufficiency or absence of finger functions.
2.Chaihu and Longgu Mulitang Regulates ERK/CREB Signaling Pathway to Ameliorate Hippocampal Nerve Injury in Mouse Model of Depression
Shiyu JI ; Li WANG ; Zhuo ZHANG ; Yingzhe GAO ; Zefeng ZHANG ; Siyu CHEN ; Guangjing XIE ; Ping WANG ; Panpan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):1-9
ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang (CLMT) on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase (ERK)/cAMP-response element-binding protein (CREB) signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control, model, low/medium/high-dose (2.89, 5.78, and 11.56 g·kg-1, respectively) CLMT, and paroxetine (10 mg·kg-1) groups. A depression model was established by chronic unpredictable mild stress (CUMS) combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1). Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. Molecular Operating Environment (MOE) software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group, the model group showed decreased sucrose preference (P0.01), increased tail-suspension immobility time (P0.01), decreased activity in the central region of the open field test (P0.01), and decreased activity in the middle and open-arm region of the elevated plus maze test (P0.01). The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells, neurons with reduced sizes and Nissl bodies, enhanced fluorescence intensity of GFAP and Iba1 (P0.01), and down-regulated expression of phosphorylated (p)-ERK, p-CREB, and BDNF (P0.05, P0.01) and mRNA levels of ERK and CREB (P0.01). Compared with the model group, the CLMT group showed increased body weight (P0.05, P0.01), restored cell morphology, with only a small number of ruptured cells, normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies, weakened fluorescence intensity of GFAP and Iba1 (P0.05, P0.01), up-regulated mRNA levels of ERK and CREB (P0.05, P0.01) and protein levels of phosphorylated (p)-ERK, p-CREB, and BDNF in the hippocampal tissue (P0.05, P0.01). The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.
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*
;
Immunotherapy, Adoptive/adverse effects*
;
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
;
Middle Aged
4.Research progress in the role of tubal ciliary movement in female infertility-related disorders.
Liuqing HE ; Yefang HUANG ; Haofei XU ; Xiaoxiao YIN ; Xinyu LUO ; Shiyu HUANG
Journal of Central South University(Medical Sciences) 2025;50(1):81-90
Tubal ciliary movement is one of the essential transport mechanisms for female fertility, playing a key role in facilitating oocyte pickup and transporting the fertilized ovum. This movement is mediated by multiciliated cells and regulated by specific proteins and hormones that modulate ciliary number, length, polarity, beat frequency, and amplitude to ensure proper function. Genetic mutations, inflammatory stimuli, and hormonal fluctuations can impair ciliary activity or induce ciliary apoptosis, leading to ciliary dysfunction. Disorders of tubal ciliary movement are frequently observed in primary ciliary dyskinesia, pelvic inflammatory disease, polycystic ovary syndrome, and endometriosis, conditions commonly associated with female infertility. These disorders manifest as structural abnormalities of cilia, disrupted polarity, shortened ciliary length, reduced ciliary count, and decreased beat frequency and amplitude. Understanding the role of tubal ciliary movement in female infertility-related diseases, through immunohistochemistry and ultrastructural analysis, helps clarify underlying infertility mechanisms. Identifying abnormal inflammatory factors, hormonal environments, and gene expression, combined with advanced techniques for measuring ciliary protein and beat frequency, may offer novel clinical targets for early prevention and treatment of female infertility.
Humans
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Female
;
Infertility, Female/etiology*
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Cilia/physiology*
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Polycystic Ovary Syndrome/physiopathology*
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Fallopian Tubes/physiopathology*
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Endometriosis/complications*
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Pelvic Inflammatory Disease/complications*
5.Ferrum@albumin assembled nanoclusters inhibit NF-κB signaling pathway for NIR enhanced acute lung injury immunotherapy.
Xiaoxuan GUAN ; Binbin ZOU ; Weiqian JIN ; Yan LIU ; Yongfeng LAN ; Jing QIAN ; Juan LUO ; Yanjun LEI ; Xuzhi LIANG ; Shiyu ZHANG ; Yuting XIAO ; Yan LONG ; Chen QIAN ; Chaoyu HUANG ; Weili TIAN ; Jiahao HUANG ; Yongrong LAI ; Ming GAO ; Lin LIAO
Acta Pharmaceutica Sinica B 2025;15(11):5891-5907
Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe3O4 loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4+/CD8+ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.
6.Dosimetric analysis of CBCT imaging frequency and matching strategy in prostate cancer radiotherapy
Yan GAO ; Xianshu GAO ; Mingwei MA ; Xueying REN ; Jiayan CHEN ; Lin MA ; Lei HUANG ; Shiyu SHANG
Chinese Journal of Radiation Oncology 2024;33(8):733-739
Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.
7.Nursing care of a patient before operation with mechanical circulation-assisted bridging heart transplantation
Xuqin LI ; Jiehui FENG ; Fangfang HUANG ; Chao YU ; Shiyu LIANG ; Xiao WANG ; Xufang LI ; Han ZHU
Chinese Journal of Nursing 2024;59(9):1114-1118
To summarize the nursing care of a patient with acute myocardial infarction complicated with cardiogenic shock before operation.The main nursing points are as follows:in the acute stage,the integrated rescue was implemented with rapid on-machine coordination of external cardiopulmonary resuscitation,multidisciplinary collaboration to ensure safe patient transport;during the bridging period,the combined operation care of extracorporeal membrane oxygenation,intra-aortic balloon counter pulsation and continuous kidney replacement therapy was carried out with goal-oriented anticoagulation care,prevention of catheter-related infection with the assistance of mechanical circulation,and neurological function monitoring.The patient successfully passed the waiting period for heart transplantation and underwent heart transplantation 21 days after admission.With the follow-up for 1 year,the patient recovered well.
8.A regression analysis of the overcorrection for the mandibular anterior teeth in trusion with clear aligners
Yangyang HUANG ; Shiyu WANG ; Hao LIU ; Li YANG ; Penglai WANG ; Changyong YUAN
STOMATOLOGY 2024;44(5):329-333,343
Objective To explore an overcorrection quantization method and related influencing factors through analyzing relationships between the achieved and preset intrusion values of mandibular anterior teeth with clear aligners.Methods Twenty pa-tients receiving Invisalign were recruited.The relative intrusion values in the ClinCheck software were recorded as the preset intrusion.The achieved intrusion values were measured through the digital model superimposition.Statistical analysis was conducted to assess the differences and linear relationships between the preset and achieved intrusion values,and investigate the effect of related factors such as intrusion amounts on the intrusion efficiency.Results For the mandibular anterior teeth,the mean intrusion efficiency was 62.2%,with the highest in the central incisors and the lowest in the canines.The intrusion amounts,incisors labial inclinations,and canine at-tachment types affected the intrusion efficiency.The differences between the preset and achieved values were significant,and the linear relationship existed.The formula of the intrusion overcorrection for the mandibular anterior teeth is"Z=(W-0.110)/0.533-W".Z re-presents the overcorrection and W represents the ideal intrusion.Conclusion The preset intrusion values in the treatment protocol could not be fully achieved.Moreover,correction should be designed in cases of mandibular canine intrusion,large amountsof intru-sion,orlingually inclined incisors.Compared to the optimized attachments,the vertical rectangular attachments on the mandibular ca-nines could improve the efficiency.
9.The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia
Shiyu DENG ; Jiawang OU ; Zicong HUANG ; Junjie CHEN ; Zihong CAI ; Qifa LIU ; Hongsheng ZHOU
Chinese Journal of Hematology 2024;45(3):257-263
Objective:To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial.Methods:We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models.Results:The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD 3) after induction therapy was independently associated with relapse risk ( HR=2.535, 95% CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk ( HR=1.869, 95% CI 1.034-3.379, P=0.039). Based on MRD 3 and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD 3-negative and IKZF1 gene deletion-negative) and high-risk (MRD 3-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % ( P<0.001) and (61.6±8.3) % vs (25.5±6.5) % ( P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS ( HR=3.937, 95% CI 1.975-7.850, P<0.001) and CIR ( HR=4.037, 95% CI 2.095-7.778, P<0.001) . Conclusion:The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.
10.Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC
Deyu ZHANG ; Fang CUI ; Kailian ZHENG ; Wanshun LI ; Yue LIU ; Chang WU ; Lisi PENG ; Zhenghui YANG ; Qianqian CHEN ; Chuanchao XIA ; Shiyu LI ; Zhendong JIN ; Xiaojiang XU ; Gang JIN ; Zhaoshen LI ; Haojie HUANG
Chinese Medical Journal 2024;137(20):2415-2428
Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

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