1.Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model
Xia QIU ; Hedong ZHANG ; Zhouqi TANG ; Yuxi FAN ; Wenjia YUAN ; Chen FENG ; Chao CHEN ; Pengcheng CUI ; Yan CUI ; Zhongquan QI ; Tengfang LI ; Yuexing ZHU ; Liming XIE ; Fenghua PENG ; Tuo DENG ; Xin JIANG ; Longkai PENG ; Helong DAI
Chinese Medical Journal 2024;137(12):1453-1464
Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.
2.Risk Factors and the Effect of Antiviral Prophylaxis for Herpes Zoster in Multiple Myeloma Patients
Li-Xia WANG ; Yan-Ping JI ; Fang LEI ; Xian-Qiu YU ; Xiao-Ming FEI
Journal of Experimental Hematology 2024;32(1):171-175
Objective:To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy.Methods:The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed,the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed.Results:Among 180 patients with multiple myeloma,23 cases developed herpes zoster(12.8%).The incidence of herpes zoster was 19.1%in patients with renal dysfunction and 23.5%after autologous hematopoietic stem cell transplantation(ASCT).The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens(21/137,15.3%)than that in those without bortezomib(2/43,4.7%),but there was no statistical difference(P=0.067).Antiviral prophylaxis was associated with fewer zoster infections,8/111(7.2%)developed herpes zoster in patients who received antiviral prophylaxis,and 15/69(21.7%)in those receiving no prophylaxis(P=0.005).65.2%of patients with herpes zoster did not receive antiviral prophylaxis.Multivariate analysis showed that bortezomib treatment,AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster,while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster.Herpes zoster had no effect on OS in patients with multiple myeloma.Conclusion:The risk of herpes zoster in multiple myeloma patients was increased.Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.
3.Primary Extranodal Diffuse Large B-Cell Lymphoma in the Rituximab Era:a Single-Center Retrospective Analysis
Lan YANG ; Li-Xia CAO ; Hui-Juan REN ; Yan-Qiu HAN
Journal of Experimental Hematology 2024;32(4):1121-1128
Objective:To investigate the clinical features and prognostic factors of patients with primary extranodal diffuse large B-cell lymphoma(DLBCL)in the rituximab era.Methods:The continuous data of newly diagnosed DLBCL patients with complete case data and first-line treated with rituximab,cyclophosphamide,epirubicin,vincristine,prednisone(R-CHOP)or R-CHOP treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to November 2023 were retrospectively analyzed.The clinical and molecular immunological features and prognosis of extranodal DLBCL were analyzed,Logistics regression model was used to analyzed the influencing factors of patients prognosis.Results:A total of 237 patients were enrolled,of which 54.4%(129 cases)were primary extranodal sources of DLBCL,and the most common extranodal sites were as follows:stomach(19.4%),colon(14.7%),tonsils(12.4%),skin/muscle(9.3%),central(7.7%),nasal/nasopharynx(6.2%),bone marrow(5.4%),testes(4.7%).The 3-year PFS and OS of DLBCL patients with extranodal involvement of bone marrow,central,liver,gastrointestinal or pulmonary origin were significantly lower than those of other patients with extranodal DLBCL of non-special site origin,and the difference was statistically significant(PFS:65.2%vs 76.7%,P=0.008;OS:82.6%vs 88.3%,P=0.04).Multivariate analysis showed that the prognostic factors affecting OS included NCCN-IPI score>3(OR:0.142,95%CI:0.041-0.495,P=0.002),non-germinal center source(OR:2.675,95%CI:1.069-6.694,P=0.036),and DEL patients(OR:0.327,95%CI:0.129-0.830,P=0.019).An NCCN-IPI score>3 was the only independent adverse prognostic factor for PFS(OR:0.235,95%CI:0.116-0.474,P<0.001).Conclusion:Patients with primary extranodal source DLBCL are more common in gastrointestinal involvement,and the overall prognosis is worse than that of patients with lymph node origin.NCCN-IPI score is an important independent adverse prognostic factor for predicting overall survival and progression-free survival in patients with primary extranodal diffuse large B-cell lymphoma.
4.Preparation Method and Quality Evaluation of Novel Frozen Human Platelets
Yi-Zhe ZHENG ; Dong-Dong LI ; Geng-Wei YAN ; Bao-Jian WANG ; Ke WANG ; Lei WANG ; Shao-Duo YAN ; Yan-Hong LI ; Qiu-Xia FU ; Zhen-Wei SUN
Journal of Experimental Hematology 2024;32(4):1264-1270
Objective:To optimize the technical parameters related to the preparation of novel frozen human platelets and formulate corresponding protocol for its preparation.Methods:Novel frozen human platelets were prepared with O-type bagged platelet-rich plasma(PRP),the key technical parameters(DMSO addition,incubation time,centrifugation conditions,etc.)of the preparation process were optimized,and the quality of the frozen platelets was evaluated by routine blood tests,apoptosis rate,platelet activation rate and surface protein expression level.Results:In the preparation protocol of novel frozen human platelets,the operation of centrifugation to remove supernatant was adjusted to before the procedure of platelets freezing,and the effect of centrifugation on platelets was minimal when the centrifugation condition was 800 xg for 8 min.In addition,platelets incubated with DMSO for 30 min before centrifugation exhibited better quality after freezing and thawing.The indexes of novel frozen human platelets prepared with this protocol remained stable after long-term cryopreservation.Conclusion:The preparation technique of novel frozen human platelets was established and the protocol was formulated.It was also confirmed that the quality of frozen platelets could be improved by incubating platelets with DMSO for 30 min and then centrifuging them at 800 ×g for 8 min in the preparation of novel frozen human platelets.
5.Halving Time of BCR-ABL Transcripts as a Precise Predictor for Deep Molecular Response in Patients with Chronic Myeloid Leu-kemia Treated with TKI
Lan YANG ; Li-Xia CAO ; Hui-Juan REN ; Yan-Qiu HAN
Journal of Experimental Hematology 2024;32(5):1349-1355
Objective:To investigate the early predictive value of halving time(HT)of BCR-ABLIS for deep molecular response(DMR)in patients with chronic myeloid leukemia(CML)treated with tyrosine kinase inhibitor(TKI).Methods:The continuous data of newly diagnosed CML patients with complete case data and first-line imatinib treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2022 were retrospectively analyzed.Combined with the clinical characteristics of the patients and the efficacy analysis at each time point,a logistic regression model was used to explore the independent influencing factors of DMR,and combined HT of BCR-ABLIS with BCR-ABLIS level at 3 months to predict DMR of the patients.Results:Univariate and multivariate analyses showed that HT and 3-month BCR-ABLIS levels were independent influencing factors for MR4,MR4.5,and stable MR4.5(P<0.05).ROC curve analysis determined that the best cut-off value of HT was 28 days.Compared with patients with HT>28 d,patients with HT ≤28 d were more likely to obtain DMR at 2,3,and 5 years,respectively(74.2%vs 27.3%,71.2%vs 22.7%,and 63.6%vs 25.0%,all P<0.001).The patients were divided into 4 groups according to BCR-ABLIS levels at 3 months and HT.Kaplan-Meier analysis showed that the patients in the BCR-ABLIS ≤10%and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABLIS≤10%and HT>28 d group(P<0.05);Patients in the BCR-ABLIS>10%and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABLIS>10%and HT>28 d group(P<0.05).Conclusion:In addition to BCR-ABLIS level,HT of BCR-ABLIS can be used as another important predictor of treatment efficacy in CML patients.The combination of BCR-ABLIS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.
6.The mediating role of emotion dysregulation between childhood trauma and anxiety in vocational school students
Yakang XIA ; Moyu QIU ; Yan ZHONG ; Hongdong DENG ; Yanping LI ; Dianying LIU
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(8):749-754
Objective:To explore the relationship between childhood trauma and anxiety in vocational school students, and to analyze the mediating role of emotion dysregulation.Methods:A cross-sectional survey was conducted in one vocational school in Ganzhou, all students completed a series of questionnaires, including the childhood trauma questionnaire (CTQ), difficulties in emotion regulation scale (DERS), and generalized anxiety disorder scale (GAD-7).The cut-off score for anxiety symptom was set GAD-7≥5.The data were analyzed using SPSS 23.0 and SPSS macro program PROCESS V4.0.Results:(1) The rate of anxiety in vocational school students was 42.96%, and girls were 27.1% higher than boys ( OR=1.271, 95% CI=1.095-1.474).(2) The CTQ (44(38, 51)) and DERS (98(89, 111)) in students with anxiety were both significantly higher than those in students without anxiety (39(34, 45), 81(73, 90), Z=-17.910, -33.859, both P<0.001).(3) Regression analysis showed that girls ( β=0.240, OR=1.271, 95% CI=1.095~1.474), childhood trauma ( β=0.028, OR=1.028, 95% CI=1.019~1.037), and emotion dysregulation ( β=0.076, OR=1.080, 95% CI=1.073-1.086) were significant predictors for anxiety.(4) Path analysis and mediating effect showed that childhood trauma positively predicted anxiety ( β=0.059, 95% CI=0.048-0.071) and emotion dysregulation ( β=0.802, 95% CI=0.749-0.854), and emotion dysregulation positively predicted anxiety ( β=0.139, 95% CI=0.132-0.145).Emotion dysregulation had a significant mediating effect (effect value=0.112, 95% CI=0.101-0.121) in the relationship between childhood trauma and anxiety, with the indirect effect accounting for 65.50% of the total effect. Conclusion:The incidence of anxiety symptoms is high among vocational school students, and childhood trauma not only directly affects anxiety symptoms, but also indirectly affects anxiety symptoms through emotion dysregulation.
7.Significance of 18F-PI-2620 PET imaging for diagnosing tau protein deposition in patients with different cognitive disorders alongside cognitive correlation analysis
Gan HUANG ; Yan ZHANG ; Cheng WANG ; Mei XIN ; Hongda SHAO ; Yue WANG ; Liangrong WAN ; Ju QIU ; Qun XU ; Jianjun LIU ; Xia LI ; Chenpeng ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(5):273-278
Objective:To evaluate the values of 18F-PI-2620 PET/CT brain imaging with SUV ratio (SUVR) in the assessment of tau protein deposition in the brain of patients with different cognitive disorders and its correlation with cognition. Methods:This was a cross-sectional study. From December 2019 to November 2022, a total of 67 subjects including 54 patients with Alzheimer′s disease (AD; 21 males, 33 females, age (68.6±7.8) years), 7 patients with mild cognitive impairment (MCI; 1 male, 6 females, age (63.1±11.2) years) and 6 healthy controls (HC; 4 males, 2 females, age (69.0±5.8) years) were enrolled retrospectively in Renji Hospital. All participants were examined by 18F-PI-2620 PET/CT. SUVRs of brain regions were obtained, including frontal lobe, temporal lobe, occipital lobe, parietal lobe, insular lobe, whole brain, as well as 10 independent brain ROIs (amygdala, orbitofrontal cortex, cingulate gyrus, superior occipital gyrus, superior parietal gyrus, inferior angular gyrus, precuneus, inferior temporal gyrus, entorhinal cortex and parahippocampal gyrus), with inferior cerebellum cortex as the reference region. All participants were estimated by cognitive scales(mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA)). One-way analysis of variance and the least significant difference t test were used to compare the differences of SUVR in each brain region among HC, MCI and AD groups. ROC curve analysis was used to determine the optimal cut-off values of SUVR in each brain region for the differential diagnosis of AD-MCI and AD-HC. Pearson correlation analysis was employed to examine the correlations of SUVR with cognitive scale scores. Results:The SUVR of whole brain was 1.40±0.31 in AD group, 1.08±0.19 in MCI group, and 1.01±0.12 in HC group. SUVR analysis in the whole brain and each brain region could distinguish AD from HC, AD from MCI ( F values: 1.76-10.09, t values: 2.98-7.47, all P<0.05), but could not distinguish HC from MCI ( t values: 0.17-1.53, all P>0.05). ROC curve analysis showed that the best cut-off value of SUVR was 1.18 for whole brain (AUC=0.89), 1.13 for amygdala (AUC=0.94) and 1.26 for parahippocampal gyrus (AUC=0.94) for differential diagnosis of AD and HC, which was 1.06 for whole brain (AUC=0.82), 1.18 for amygdala (AUC=0.88) and 1.28 (AUC=0.88) for infratemporal gyrus to differential diagnosis of AD and MCI. SUVRs of the whole brain, frontal, occipital, parietal, temporal and insula were significantly negatively correlated with MMSE and MoCA cognitive scale scores ( r values: from -0.64 to -0.40, all P<0.05). Conclusions:SUVR quantitative analysis in 18F-PI-2620 PET imaging can assist the differential diagnosis of AD and HC, AD and MCI. The SUVRs of whole brain and five lobes show negative correlations with MMSE and MoCA scores.
8.Diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease in patients with memory impairment
Yan ZHANG ; Chenpeng ZHANG ; Gan HUANG ; Cheng WANG ; Mei XIN ; Hongda SHAO ; Yue WANG ; Liangrong WAN ; Ju QIU ; Qun XU ; Xia LI ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(12):712-717
Objective:To assess the diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease (AD) in patients with memory impairment. Methods:A retrospective analysis was conducted on 96 patients (40 males, 56 females, age: 69.0(62.8, 74.0) years) initially diagnosed with memory impairment in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2019 and September 2023. The amyloid-tau-neurodegeneration (ATN) criteria, based on 18F-AV45+ 18F-PI-2620 PET/CT+ MRI imaging results, were used as the diagnostic standard for AD. Visual analysis (temporoparietal or posterior cingulate cortex (PCC) hypometabolism) and semi-quantitative analysis methods (PET-SCORE and NeuroQ software analysis (SUV ratio, SUVR)) were applied to evaluate the diagnostic efficiency of 18F-FDG PET imaging for AD. Diagnostic efficiencies of visual assessment and semi-quantitative parameters were compared by χ2 test. Additionally, Pearson correlation analysis was performed to examine the relationship between results of PET-SCORE and cognitive scales. Results:Of the 96 patients initially diagnosed with memory impairment, 61 were clinically diagnosed with AD, while 35 were non-AD patients. Visual assessment of temporoparietal hypometabolism showed the highest sensitivity (91.80%, 56/61), which was significantly different from the sensitivities of PET-SCORE (40.98%(25/61); χ2=29.03, P<0.001) and visual assessment of PCC hypometabolism (77.05%(47/61); χ2=5.82, P=0.016). While semi-quantitative assessment using PET-SCORE demonstrated the highest specificity (100%, 35/35), which was significantly different from the specificities of visual assessment methods (temporoparietal hypometabolism: 17.14%(6/35), χ2=27.03, P<0.001; PCC hypometabolism: 54.29%(19/35), χ2=14.06, P<0.001). PET-SCORE exhibited statistically significant correlations with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scores ( r values: -0.38, -0.36, 0.31, all P<0.01). Conclusions:Among patients initially diagnosed with memory impairment, visual assessment in 18F-FDG PET imaging analysis demonstrates higher sensitivity, while semi-quantitative analysis using PET-SCORE exhibits higher specificity. PET-SCORE shows statistically significant correlation with the severity of cognitive decline.
9.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
10.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

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