1.Effect of auricular therapy on sleep improvement and the GABAergic system pathway in an insomnia rat model
Hao CHEN ; Xifen ZHANG ; Xuesong WANG ; Yuanbo GAO ; Xuxin LI ; Xihui ZHENG ; Yu WANG ; Xiaojun ZHENG ; Haiping LI ; Yanfen SHE
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):138-148
Objective:
To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism.
Methods:
According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats.
Results:
Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05).
Conclusion
Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.
2.Effect of high-definition transcranial direct current stimulation combined with upper limb robot on upper limb dysfunction after ischemic stroke
Xiaojun WANG ; Hani WANG ; Hong YU ; Yuanmei LI ; Yuda ZHOU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(2):218-224
ObjectiveTo investigate the effect of high-definition transcranial direct current stimulation (HD-tDCS) combined with upper limb robot on upper limb dysfunction in patients with ischemic stroke. MethodsFrom January, 2023 to March, 2024, 56 inpatients with upper limb dysfunction after ischemic stroke were selected from Zhejiang Rehabilitation Medical Center, and divided into control group (n = 28) and experimental group (n = 28) randomly. All the patients received comprehensive treatment and upper limb robot training, while the control group received sham HD-tDCS and the experimental group received HD-tDCS, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Wolf Motor Function Test (WMFT) and modified Barthel Index (MBI) before and after treatment. The cortical amplitude, cortical latency and central motor conduction time (CMCT) of transcranial magnetic stimulation motor-evoked potential (MEP) were recorded, and a correlation analysis was conducted. ResultsThe scores of FMA-UE, WMFT and MBI, and MEP cortical amplitude, cortical latency and CMCT improved in both groups after treatment (t > 3.177, P < 0.01), and they were better in the experimental group than in the control group (t > 3.610, P < 0.01). The scores of FMA-UE and WMFT negatively correlated with MEP cortical latency and CMCT, and positively correlated with MEP cortical amplitude (|r| > 0.448, P < 0.001). ConclusionHD-tDCS is effective on upper limb motor function and activities of daily living for patients with ischemic stroke, and can improve corticospinal motor conduction.
3.Value of Serum D-Lactic Acid,I-FABP,and E-Selectin in Early Diagnosis of Infection After Gastrointestinal Surgery and Their Relationship with Curative Effect and TCM Syndromes
Xiaojun SHEN ; Yongpan LIU ; Senquan YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):159-166
ObjectiveTo investigate the value of serum D-lactic acid,intestinal fatty acid binding protein (I-FABP),and E-selectin (Es) in early diagnosis of infection after gastrointestinal surgery and their relationship with curative effect and traditional Chinese medicine (TCM) syndromes. MethodsForty-nine patients with abdominal infection after gastrointestinal surgery treated in Xianju County Traditional Chinese Medicine Hospital from June 2020 to August 2023 were selected as the infection group,and another 53 non-infected patients after gastrointestinal surgery were selected as the non-infected group. The serum D-lactic acid,I-FABP,and Es levels at the first,third,fifth, and seventh days after surgery were compared between the two groups,and the Pearson correlation coefficient was used to analyze the correlation of serum indexes. The receiver operating (ROC) curve and the area under the curve (AUC) of the patients were analyzed to analyze the value of each serum index in diagnosing infection after gastrointestinal surgery. At the same time,the serum indexes of patients with different therapeutic effects were monitored dynamically on the first,third,fifth, and seventh days of treatment. Logistic regression was used to analyze the relationship between serum indexes and curative effect. The relationship between TCM syndromes and serum indexes was analyzed. ResultsThe levels of serum D-lactic acid,I-FABP,and Es in the two groups decreased on the first,third,fifth, and seventh days. There were significant differences among groups, time, and interaction (P<0.01). On the third day,serum D-lactic acid was positively correlated with I-FABP and Es,and I-FABP was positively correlated with Es (P<0.01). On the third day after surgery,the AUC of D-lactic acid + I-FABP + Es in the diagnosis of infection after gastrointestinal surgery was 0.861,higher than 0.727 of D-lactic acid,0.745 of I-FABP, and 0.797 of Es (P<0.05). The levels of serum D-lactic acid,I-FABP,and Es in patients with remission infection were decreased continuously on the first,third,fifth,and seventh days. Patients with exacerbation of infection showed a continuous upward trend,and there were significant differences among groups, time, and interaction (P<0.01). The TCM syndromes of the patients were heat toxicity syndrome,acute deficiency syndrome,blood stasis syndrome, and fu-Qi obstruction syndrome,accounting for 61.22%,20.41%,12.24%, 6.12% respectively. There were no significant differences in different syndromes,time, and interaction. ConclusionSerum D-lactic acid,I-FABP,and Es can be used for early diagnosis of abdominal infection after gastrointestinal surgery,and the change of indicators can reflect the therapeutic effect and prognosis of patients with infection,but there is no significant correlation between the change of indicators and TCM syndromes.
4.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
5.Risk factors for positive post-transplantation measurable residual disease in patients with acute lymphoblastic leukemia.
Yuewen WANG ; Guomei FU ; Lanping XU ; Yu WANG ; Yifei CHENG ; Yuanyuan ZHANG ; Xiaohui ZHANG ; Yanrong LIU ; Kaiyan LIU ; Xiaojun HUANG ; Yingjun CHANG
Chinese Medical Journal 2025;138(9):1084-1093
BACKGROUND:
The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS:
A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis.
RESULTS:
Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P = 0.027; P = 0.003; P = 0.035; P = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival.
CONCLUSION
Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*
;
Neoplasm, Residual
;
Hematopoietic Stem Cell Transplantation/methods*
;
Male
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Female
;
Risk Factors
;
Adolescent
;
Adult
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Child
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Child, Preschool
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Young Adult
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Middle Aged
;
Infant
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Transplantation, Homologous
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Proportional Hazards Models
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Retrospective Studies
6.Epidemiological characteristics and immunization history of pertussis cases in Yichang City 2018 - 2023
Weiwei WANG ; Xiaojun LIU ; Yi YAN ; Jing JIANG ; Qiujing YU ; Wei JIANG ; Li GUO ; Jialian YU ; Guiwen LI ; Qiwei WANG
Journal of Public Health and Preventive Medicine 2025;36(6):86-89
Objective To analyze the epidemiological characteristics and immunization history of pertussis cases in Yichang City, Hubei Province from 2018 to 2023. Methods Data on the incidence and immunization history of pertussis cases were collected in Yichang City from 2018 to 2023, and the epidemiological characteristics was analyzed and described. Results A total of 109 cases of pertussis were reported in Yichang from 2018 to 2023, and the annual average reported incidence rate was 0.45/100,000. The incidence rate reported in each year was between 0~1.58/100,000. The area with the highest annual reported incidence rate was Xiling District (1.19/100,000). There was a statistically significant difference in the incidence rate between different years (χ2=208.26, P < 0.001). The annual reported incidence rate showed a significant increasing trend (χ2 trend =125.71, P < 0.001). The ratio of male to female cases was 1.22. There was no significant difference in the annual reported incidence rates between males and females (χ2=0.85, P=0.36). Children aged 3-9 years accounted for 60.55%. Students and scattered children accounted for 45.87% and 36.70%, respectively. Before the onset of the disease, 72.48% had a history of immunization with pertussis-containing vaccine, and 27.52% had no history of immunization. The shortest interval between the last dose of pertussis-containing vaccine and the onset of the disease was 8 days, the longest was 4057 days, and the median was 1882 days. Conclusion From 2018 to 2023, the reported incidence of pertussis in Yichang City has been on the rise, with the majority of cases occurring in children and students under the age of 9. It is recommended to strengthen pertussis disease monitoring.
7.Long-term efficacy of CMV/EBV bivirus-specific T cells for viral co-reactivation after stem cell transplantation.
Xuying PEI ; Meng LV ; Xiaodong MO ; Yuqian SUN ; Yuhong CHEN ; Chenhua YAN ; Yuanyuan ZHANG ; Lanping XU ; Yu WANG ; Xiaohui ZHANG ; Xiaojun HUANG ; Xiangyu ZHAO
Chinese Medical Journal 2025;138(5):607-609
8.Preemptive immunotherapy for KMT2A rearranged acute leukemias post-allogeneic stem cell transplantation.
Jing LIU ; Shuang FAN ; Xiaohui ZHANG ; Lanping XU ; Yu WANG ; Yifei CHENG ; Chenhua YAN ; Yuhong CHEN ; Yuanyuan ZHANG ; Meng LV ; Yazhen QIN ; Xiaosu ZHAO ; Xiaojun HUANG ; Xiaodong MO
Chinese Medical Journal 2025;138(22):3034-3036
9.Brain computer interface nursing bed control system based on deep learning and dual visual feedback.
Pai WANG ; Xingxing JI ; Jiali WANG ; Xiaojun YU
Journal of Biomedical Engineering 2025;42(5):1021-1028
In order to meet the need of autonomous control of patients with severe limb disorders, this paper designs a nursing bed control system based on motor imagery-brain computer interface (MI-BCI). In view of the low decoding performance of cross-subjects and the dynamic fluctuation of cognitive state in the existing MI-BCI technology, the neural network structure optimization and user interaction feedback enhancement are improved. Firstly, the optimized dual-branch graph convolution multi-scale neural network integrates dynamic graph convolution and multi-scale convolution. The average classification accuracy is higher than that of multi-scale attention temporal convolution network, Gram angle field combined with convolution long short term memory hybrid network, Transformer-based graph convolution network and other existing methods. Secondly, a dual visual feedback mechanism is constructed, in which electroencephalogram (EEG) topographic map feedback can improve the discrimination of spatial patterns, and attention state feedback can enhance the temporal stability of signals. Compared with the single EEG topographic map feedback and non-feedback system, the average classification accuracy of the proposed method is also greatly improved. Finally, in the four classification control task of nursing bed, the average control accuracy of the system is 90.84%, and the information transmission rate is 84.78 bits/min. In summary, this paper provides a reliable technical solution for improving the autonomous interaction ability of patients with severe limb disorders, which has important theoretical significance and application value.
Humans
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Brain-Computer Interfaces
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Deep Learning
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Electroencephalography
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Feedback, Sensory
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Neural Networks, Computer
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Beds
10.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.


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