2.Function of miR-19a and miR-92a determined by seed-targeting inhibition in multiple myeloma cells and their signal pathway analysis
Maoxiao FENG ; Chunming GU ; Zhao YIN ; Tianfu LI ; Yuyu ZHAO ; Weipeng LIANG ; Ruirui WANG ; Jia FEI
Chinese Journal of Pathophysiology 2015;(8):1505-1509
AIM:TostudythefunctionofmicroRNA(miR)-19aandmiR-92abyseed-targetinginhibitionin multiple myeloma cells and their signal pathways .METHODS:The experiments were divided into t-antimiR-19a group, t-antimiR-92a group, scramble control group and blank control group .The growth-inhibitory potencies were measured by MTT assay.The ability of cell colony formation was measured by cell colony formation assay .The ability of cell invasion was measured by Transwell experiment .The miR-19a and miR-92a target gene signal pathways were integrated by miRFo-cus software.RESULTS:MTT assay showed that t-antimiR-19a and t-antimiR-92a significantly inhibited the viability of multiple myeloma cells , and the best concentration and time were 0.5μmol/L and 48 h, respectively .The colony number in t-antimiR-19a/92a group was less than that in scramble control group .The transfection with t-antimiR-19a or t-antimiR-92a effectively decreased the cell invasion , as the relative invasion cell number was significantly decreased compared with scramble control group.miR-19a and miR-92a were involved in mTOR signaling, cell cycle and other cancer pathways . CONCLUSION:miR-19a and miR-92a cluster might be a potential target for therapeutic intervention in multiple myelo-ma.
3.Clinical study of lamotrigine add-on therapy for drug-resistant epilepsy in children
Lei LIU ; Yan DONG ; Dan XU ; Xiaoli ZHANG ; Junxin WANG ; Ruirui LIANG ; Tianming JIA
International Journal of Pediatrics 2022;49(6):423-428
Objective:To summarize the clinical characteristics of drug-resistant epilepsy (DRE) in children and to analyze the efficacy of lamotrigine (LTG) add-on therapy for DRE in children of different seizure type, syndrome and etiological category.Methods:All cases of DRE patients treated with LTG or other antiseizure medication (ASM) adjunctive therapy in the Third Affiliated Hospital of Zhengzhou University from May 2019 to April 2020 were collected.The LTG add-on therapy group was treated with LTG add-on therapy, and the control group was treated with other ASM add-on therapy.The therapeutic effects of the two groups were compared.Results:A total of 134 cases meeting the requirement of research were collected, including 98 cases in the LTG add-on therapy group and 36 cases in the control group.For seizure of focal onset and unknown origin, there was statistical difference in efficacy between the LTG add-on therapy group and the control group ( Z=-2.48、-2.11, P<0.05), but for generalized DRE in children, there was no statistical difference in efficacy between the two groups ( Z=-0.39, P>0.05). There was a significantly statistical difference in curative effect between the LTG add-on therapy group and the control group for childhood DRE which could not be classified as any epileptic syndrome ( Z=-3.99, P<0.01), but there was no statistical difference in efficacy between the two groups for West syndrome and benign epilepsy accompanied by central temporal spikes ( Z=-0.94、-1.22, P>0.05). For childhood intractable epilepsy with unknown etiology, there was statistical difference in efficacy between the LTG add-on therapy group and the control group ( Z=-1.96, P<0.05), and for childhood intractable epilepsy with structural etiology, there was significantly statistical difference in efficacy between the two groups ( Z=-3.07, P<0.01), but there was no statistical difference in the efficacy for childhood intractable epilepsy with genetic etiology between the two groups ( Z=-1.02, P>0.05). Conclusion:The efficacy of LTG add-on therapy is significantly better than others for childhood DRE with seizure of focal onset or unknown origin, childhood DRE unclassified to any syndrome, and childhood DRE with structural etiology and unknown origin, especially with structural etiology.
4.Factors associated with poor short-term pharmacotherapy response in self-limited epilepsy with centrotemporal spikes
Ruirui LIANG ; Dan XU ; Jing GUAN ; Xiaoli ZHANG ; Tiansi CAO ; Yaoyao CHEN ; Tianming JIA
Chinese Journal of Applied Clinical Pediatrics 2023;38(5):365-369
Objective:To explore risk factors for clinical onset in children with uncontrolled self-limited epilepsy with centrotemporal spikes (SeLECTS) managed by 2 anti-seizure medications (ASMs).Methods:A total of 112 children with SeLECTS who were diagnosed at the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University from January 2018 to May 2021 were retrospectively reviewed.All of them were treated with conventional ASMs, and regularly followed up for 1-2 years.Types of therapeutic drugs, clinical seizure control status, presence of new seizure forms, electroencephalogram (EEG) were reviewed at follow-up visits.According to whether the seizures were controlled after the use of no more than 2 ASMs, patients were divided into poor response group (43 cases) and good response group (69 cases), and their clinical data and EEG characteristics were compared.Multivariate Logistic regression analysis was used to explore the risk factors for seizures that were uncontrolled by 2 ASMs. Results:There were significant differences in the age of onset ( χ2=8.919, P=0.003), seizure form ( χ2=4.218, P=0.040), seizure frequency ( Z=-7.664, P<0.001), EEG background slowing ( χ2=10.284, P=0.001), emergence of electrical status epilepticus during slow-wave sleep (ESES)( χ2=11.921, P=0.001), discharge generalization ( χ2=25.377, P<0.001), and presence of epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS)( χ2=54.334, P<0.001) between groups.Multivariate Logistic regression analysis showed that seizure frequency ( P<0.001, OR=0.086, 95% CI: 0.022-0.329), discharge generalization ( P=0.006, OR=9.942, 95% CI: 1.918-51.527) and EEG background slowing ( P=0.041, OR=6.648, 95% CI: 1.077-41.038) were the 3 main risk factors associated with poor response to short-term medications of ASMs. Conclusions:Seizures are easily controlled in most SeLECTS patients medicated with ASMs with a favorable prognosis.Seizure frequency, discharge generalization and EEG background slowing are risk factors for the poor response to short-term pharmacotherapy in children with SeLECTS.
5.Remnant cholesterol is associated with triglyceride and glucose index in young and middle-aged patients with ischemic stroke
Youyou ZHANG ; Ruirui JIA ; Long WANG ; Dong CHEN ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(6):910-914
【Objective】 To investigate the association between remnant cholesterol (RC) and triglyceride and glucose (TyG) index in young and middle-aged patients with ischemic stroke. 【Methods】 A total of 268 patients were divided into two groups, namely low TyG index group (n=134) and high TyG index group (n=134). Characteristics of the study population and metabolism risk factors (TC, TG, HDL-C, LDL-C, UA) were collected from biochemical test results. Spearman correlation analysis was used to analyze the correlation between metabolism risk factors and TyG index. Multivariate conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for RC and TyG index. 【Results】 Compared with the low TyG index group, significant differences were observed for BMI, history of diabetes, history of hypertension, SBP, DBP, FBG, TC, TG, LDL-C, RC, UA, and TyG index in high TyG index group. No significant differences were observed in age, gender, smoking status, or drinking status, HDL-C between the two groups. Spearman correlation analysis indicated that significant linear associations were observed between BMI, SBP, DBP, FBG, TC, TG, HDL-C, LDL-C, RC, UA and TyG index. Logistic regression analysis revealed that the RC, BMI, hypertension, diabetes, TC, LDL-C, and UA were significantly associated with the risk of increased level of TyG index. After adjusted analysis by RC, BMI, hypertension, diabetes, TC, LDL-C, and UA, only RC was significantly associated with an increased risk of increased level of TyG index. 【Conclusion】 Remnant cholesterol was associated with an increased risk of elevated TyG index level in young and middle-aged patients with ischemic stroke.
6.Association between impaired sensitivity to thyroid hormones and ischemic stroke in euthyroid population with hypertension and sex difference in this association
Youyou ZHANG ; Ruirui JIA ; Long WANG ; Dong CHEN ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):763-768
【Objective】 To investigate the associations between thyroid hormone sensitivity indices in euthyroid patients with hypertension and the risk of ischemic stroke, as well as gender difference in this association. 【Methods】 We selected 760 hypertensive patients admitted to the Geriatric Neurology Department and outpatient clinic in The Second Affiliated Hospital of Xi’an Jiaotong University between April 2021 and May 2022. We collected their basic characteristics, blood biochemical parameters, thyroid indices, and brain magnetic resonance imaging information. All the patients were divided into two groups based on the clinical manifestations and brain magnetic resonance imaging: hypertension combined with ischemic stroke (n=526) and control (n=234) groups. Independent sample t-tests or non-parametric tests were used to compare the differences in thyroid hormone sensitivity indicators between the two groups. Spearman correlation analysis was used to analyze the correlation between serum thyroid indices and ischemic stroke. Multivariate conditional Logistic regression analysis was made to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid indices and ischemic stroke. 【Results】 There were statistically significant differences between the two groups in terms of age, gender, TC, LDL-c, HDL-c, systolic blood pressure, FT3/FT4, TFQI, and PTFQI (all P<0.05). However, there was no statistically significant difference between the two groups in weight, smoking, drinking, history of diabetes, TG, FBG, diastolic blood pressure, TSHI, or TT4RI (all P>0.05). The results of Spearman correlation analysis showed a negative correlation between FT3/FT4 and ischemic stroke (P<0.05), but a positive correlation of TFQI and PTFQI with ischemic stroke (P<0.05) in euthyroid patients with hypertension. Logistic regression analysis showed that FT3/FT4 was significantly associated with ischemic stroke in euthyroid patients with hypertension (P=0.001), with OR (95% CI) of 0.001 (0.000, 0.058). After stratifying by gender, Logistic regression analysis found that FT3/FT4, TFQI, and PTFQI were associated with an increased risk of ischemic stroke in female patients, with OR (95% CI) of 0.000 (0.000, 0.001), 3.132 (1.415, 6.930), and 3.010 (1.406, 6.445), respectively. 【Conclusion】 Lower serum FT3/FT4 ratio is associated with an increased risk of ischemic stroke in euthyroid patients with hypertension, and the significant association of TFQI and PTFQI with the risk of ischemic stroke is found in females.
7.Impaired sensitivity to thyroid hormones is associated with ischemic stroke in young and middle-aged euthyroid population
Youyou ZHANG ; Ruirui JIA ; Dong CHEN ; Fuhua GONG ; Long WANG ; Hui WANG ; Zhaoyang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(6):938-943
【Objective】 To investigate the association of thyroid indices with the prevalence of ischemic stroke in young and middle-aged euthyroid population. 【Methods】 For this retrospective study, 620 euthyroid patients aged from 18 to 65 years were divided into ischemic stroke group (n=308) and non-ischemic stroke group (n=312). The characteristics of the study population; serum thyroid indices, i.e., free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH), were collected from biochemical test results. Multivariate conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid indices and ischemic stroke. 【Results】 Compared with non-ischemic stroke group, significant differences were observed in age, gender, weight, smoking status, drinking status, history of hypertension and diabetes, SBP, DBP, FBG, TC, HDL-C, LDL-C, FT3, FT4, FT3/FT4, TFQI, and PTFQI in ischemic stroke patients (all P<0.05). No significant differences were observed for TG, TSH, TSHI, or TT4RI between the two groups (all P>0.05). Logistic regression analysis revealed that lower FT3 [OR (95% CI) =0.722 (0.547~0.955) , P=0.022] and FT3/FT4 ratio [OR (95% CI) =0.723 (0.600~0.870) , P=0.001] , FT4 [OR (95% CI) =1.099 (1.011~1.194) , P=0.026] were significantly associated with an increased risk of ischemic stroke. After stratified analysis by hypertension, FT4 [OR (95% CI) =1.133 (1.021~1.257) , P=0.019] , lower FT3/FT4 ratio [OR (95% CI) =0.723 (0.600~0.870) , P=0.003] , TFQI [ OR (95% CI) =1.854 (1.026~3.350) , P=0.041] , and PTFQI [OR (95% CI) =1.871 (1.065~3.288) , P=0.029] were significantly associated with an increased risk of ischemic stroke in patients combined with hypertension, while after stratified analysis by diabetes, we only found that lower FT3/FT4 ratio [OR (95% CI) =0.730 (0.559~0.953) , 0.704 (0.536~0.944) , P=0.021] and FT4 [OR (95% CI) =1.170 (1.025~1.335) , P=0.026] were significantly associated with an increased risk of ischemic stroke in patients combined with diabetes. 【Conclusion】 FT3, FT4, and FT3/FT4 ratio are associated with an increased risk for ischemic stroke in young and middle-aged euthyroid population; TFQI and PTFQ are associated with an increased risk for ischemic stroke in patients combined with hypertension.
8.Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy.
Delin KONG ; Tingting YANG ; Jia GENG ; Ruirui JING ; Qiqi ZHANG ; Guoqing WEI ; He HUANG ; Yongxian HU
Journal of Zhejiang University. Science. B 2022;23(10):876-880
Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Adult
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Antigens, CD19
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Hematopoietic Stem Cell Transplantation
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Humans
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Immunotherapy, Adoptive/adverse effects*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
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Receptors, Chimeric Antigen
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Recurrence