1.Effects of conditioned medium of acute myeloid leukemia on biology of mesenchymal stem cells
Chike ZHANG ; Feiqing WANG ; Dan WU ; Bo YANG ; Jinyang CHENG ; Juan CHEN ; Dongxin TANG ; Yang LIU ; Yanju LI
Chinese Journal of Tissue Engineering Research 2024;28(31):4995-5002
BACKGROUND:At present,the biological functions and molecular changes of bone marrow mesenchymal stem cells in the tumor microenvironment of acute myeloid leukemia are still unclear. OBJECTIVE:To explore the changes in the biological function of bone marrow mesenchymal stem cells in acute myeloid leukemia and the role of acute myeloid leukemia conditioned medium by bioinformatics and experiment. METHODS:Differential genes were screened from GEO data sets,and enrichment analysis was performed.The protein-protein interaction network was constructed and the Hub gene was obtained.Bone marrow mesenchymal stem cells from patients with acute myeloid leukemia and healthy donors were cultured.Bone marrow mesenchymal stem cells from healthy donors were treated with acute myeloid leukemia conditioned culture solution.Each group was subjected to the adipogenic differentiation,osteogenic differentiation,staining of β-galactosidase,detection of the cell cycle,and validation of Hub genes. RESULTS AND CONCLUSION:(1)Gene expression data of bone marrow mesenchymal stem cells from acute myeloid leukemia patients and healthy donors were obtained from GSE84881,and 184 up-regulated genes and 140 down-regulated genes were screened.(2)The biological functions of enrichment mainly include cell cycle,adipocyte differentiation,cell metabolism,and MYC pathway.According to the Degree algorithm,10 up-regulated Hub genes and 10 down-regulated Hub genes were selected.(3)The cell in vitro experiment found that:compared with the control group,the surface antigen of acute myeloid leukemia mesenchymal stem cells did not change,but it showed enhanced lipid differentiation ability,weakened osteogenic differentiation ability,increased β-galactosidase positive cell number,altered cell morphology,arrested cell cycle,increased LGALS3 expression,and decreased MYC expression.Mesenchymal stem cells from healthy donors showed similar changes after being cultured in acute myeloid leukemia conditioned medium.(4)The results show that biological function of mesenchymal stem cells is altered in the acute myeloid leukemia microenvironment,which provides new insights into the interaction between mesenchymal stem cells and tumor cells.
2.Longitudinal extrauterine growth restriction in extremely preterm infants: current status and prediction model
Xiaofang HUANG ; Qi FENG ; Shuaijun LI ; Xiuying TIAN ; Yong JI ; Ying ZHOU ; Bo TIAN ; Yuemei LI ; Wei GUO ; Shufen ZHAI ; Haiying HE ; Xia LIU ; Rongxiu ZHENG ; Shasha FAN ; Li MA ; Hongyun WANG ; Xiaoying WANG ; Shanyamei HUANG ; Jinyu LI ; Hua XIE ; Xiaoxiang LI ; Pingping ZHANG ; Hua MEI ; Yanju HU ; Ming YANG ; Lu CHEN ; Yajing LI ; Xiaohong GU ; Shengshun QUE ; Xiaoxian YAN ; Haijuan WANG ; Lixia SUN ; Liang ZHANG ; Jiuye GUO
Chinese Journal of Neonatology 2024;39(3):136-144
Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.
3.Three-dimensional genomic characterization of two multiple myeloma patients with normal karyotype and complex karyotype
Yue WANG ; Mengsi CHEN ; Ming CHEN ; Yanju LI ; Xiaohong GUAN ; Lihua LEI ; Li TAO ; Xiaoxiao LIU ; Dong HE ; Xiaoli FEI ; Kaiji ZHANG
Chinese Journal of Blood Transfusion 2024;37(11):1247-1255
[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.
4.Exercise promotes irisin expression to ameliorate renal injury in type 2 diabetic rats
Fengmin ZHOU ; Yanju GUO ; Ning CHEN
Journal of Southern Medical University 2024;44(4):675-681
Objective To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats. Methods Forty male SD rats aged 4-6 weeks were randomized into normal control group, type 2 diabetes mellitus model group, diabetic exercise (DE) group and diabetic irisin (DI) group (n=8). The rats in DE group were trained with treadmill running for 8 weeks, and those in DI group were given scheduled irisin injections for 8 weeks. After the treatments, blood biochemical parameters of the rats were examined, and renal histopathology was observed with HE, Masson and PAS staining. Western blotting was used to detect the protein expression levels in the rats' kidneys. Results The diabetic rats showed significantly increased levels of fasting insulin, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen with lowered serum irisin level (all P<0.05). Compared with those in DM group, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups (all P<0.05). The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys, which were significantly improved in DE group and DI group. Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5, LC3-Ⅱ/Ⅰ, Atg7, Beclin-1, p-AMPK, AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats (all P<0.05). Conclusion Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.
5.Exercise promotes irisin expression to ameliorate renal injury in type 2 diabetic rats
Fengmin ZHOU ; Yanju GUO ; Ning CHEN
Journal of Southern Medical University 2024;44(4):675-681
Objective To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats. Methods Forty male SD rats aged 4-6 weeks were randomized into normal control group, type 2 diabetes mellitus model group, diabetic exercise (DE) group and diabetic irisin (DI) group (n=8). The rats in DE group were trained with treadmill running for 8 weeks, and those in DI group were given scheduled irisin injections for 8 weeks. After the treatments, blood biochemical parameters of the rats were examined, and renal histopathology was observed with HE, Masson and PAS staining. Western blotting was used to detect the protein expression levels in the rats' kidneys. Results The diabetic rats showed significantly increased levels of fasting insulin, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen with lowered serum irisin level (all P<0.05). Compared with those in DM group, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups (all P<0.05). The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys, which were significantly improved in DE group and DI group. Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5, LC3-Ⅱ/Ⅰ, Atg7, Beclin-1, p-AMPK, AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats (all P<0.05). Conclusion Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.
6.Correlation of telomere length of bone marrow mononuclear cells with relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia
Bo DENG ; Jishi WANG ; Yan ZHANG ; Yinghao LU ; Yanju LI ; Yi HUANG ; Mengxing LI ; Ying CHEN ; Rui GAO ; Xiao CHAI ; Yun ZHAN ; Jie XIONG ; Peng ZHAO
Journal of Leukemia & Lymphoma 2023;32(6):335-342
Objective:To investigate the relationship between telomere length of bone marrow mononuclear cells and prognosis of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Telomere length of bone marrow mononuclear cells before transplantation, after transplantation and before donor mobilization as well as information related to follow-up of 33 AML patients who received allo-HSCT in the Affiliated Hospital of Guizhou Medical University between June 2020 and June 2021 were retrospectively analyzed. Telomere length was detected by using telomeric terminal restriction fragment (TRF) method. Telomere length was compared among patients with different prognoses. The recurrence within 1 year was treated as the gold standard and receiver operating characteristic (ROC) curve was used to analyze the effect of telomere length before transplantation or before donor mobilization in the judgement of the recurrence within 1 year after transplantation. The patients were stratified according to the optimal threshold value of telomere length for patients or donors, and Kaplan-Meier method was used to compare the progression-free survival (PFS) of patients with different stratification, and log-rank test was performed.Results:The median age of 33 patients was 34 years (14-61 years), and there were 17 males and 16 females; 31 patients were initially diagnosed with AML, 1 patient transferred from myelodysplastic syndrome (MDS) to AML, and 1 patient transferred from chronic granulocytic leukemia (CML) to AML; 14 received identical sibling transplantation and 19 received haploidentical sibling transplantation. The median age of the donors was 30 years (20-65 years), including 24 males and 9 females. Telomere length of bone marrow mononuclear cells before mobilization in 33 donors was longer than that in patients before transplantation (33 cases) and at +30 d after transplantation (31 cases) [(6.67±0.31) kb, (6.40±0.33) kb, (6.48±0.33) kb, respectively; all P < 0.05], and the difference between patients before and at +30 d after transplantation was not statistically significant ( t = 0.89, P = 0.378), and the telomere length of bone marrow mononuclear cells in 11 patients +180 d after transplantation was (6.66±0.18) kb. The incidence of acute graft-versus-host disease (aGVHD) after transplantation was 45.5% (15/33), the incidence of infection with clear imaging and pathogenic basis was 39.4% (13/33), the mortality rate within 1 year after transplantation was 3.0% (1/33), and the recurrence rate within 1 year after transplantation was 15.2% (5/33). There were no statistically significant differences in telomere length of donor pre-mobilization bone marrow mononuclear cells between the groups with and without aGVHD and between the infected and non-infected groups (all P > 0.05).Compared with patients who had not relapsed within 1 year after transplantation, telomere length of donor pre-mobilization bone marrow mononuclear cells was shorter in patients who relapsed within 1 year after transplantation [(6.39±0.19) kb vs. (6.72±0.30) kb, t = -3.23, P = 0.011], telomere length was longer in patients before transplantation [(6.75±0.16) kb vs. (6.35±0.36) kb, t = 4.17, P = 0.001]. ROC curve analysis showed that the optimal threshold values for telomere length of pre-transplantation and donor pre-mobilization bone marrow mononuclear cells were 6.48 and 6.42 kb, respectively for patients who relapsed within 1 year after transplantation. PFS in patients with pre-transplantation bone marrow mononuclear cells telomere length < 6.48 kb was better than that in patients with telomere length ≥ 6.48 kb ( P = 0.003); PFS in patients with pre-mobilization bone marrow mononuclear cells telomere length>6.42 kb was better than that in patients with telomere length ≤ 6.42 kb ( P < 0.001). Conclusions:In allo-HSCT for AML, patients have an increased risk of relapse within 1 year after transplantation when their pre-transplantation bone marrow mononuclear cells telomere length is long and the donor bone marrow mononuclear cells telomere length is short.
7.The curative effect of Tongdu Tiaoshen acupuncture on hemiplegia after stroke and its influence on nerve function and limb function
Yanju LI ; Shanbin SUN ; Hui LIU ; Yueguang LIANG ; Chong CHEN
International Journal of Traditional Chinese Medicine 2023;45(6):679-683
Objective:To explore the application of Tongdu Tiaoshen acupuncture in patients with hemiplegia after stroke.Methods:Randomized controlled trial. A total of 70 patients who met the inclusion criteria for post-stroke hemiplegia in our hospital from January 2020 to December 2021 were divided into two groups, with 35 cases in each group, according to the random number table. The control group was given conventional treatment combined with rehabilitation exercise therapy, and the observation group was given Tongdu Tiaoshen acupuncture on the basis of the above, and both groups were treated continuously for 1 month. Compare of the two groups Fugl-Meyer Assessment (FMA), Modified Ashworth Scale (MAS), National Institutes of Health Stroke Scale (NIHSS), Activity of Daily Living (ADL) score; Brunnstrom stage method was used to assess the patient's motor ability, and Holden walking function grade was used to assess the patient's walking ability. The activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time(TT), and serum fibrinogen (FIB), D-dimer (D-D), plasminogen activator inhibitor 1 (PAI-1) levels were observed by ELISA. Adverse events were recorded and clinical efficacy was evaluated.Results:The total effective rates of the observation group and the control group were 97.14% (34/35) and 77.14% (27/35), respectively, and the difference between the two groups was statistically significant ( χ2=6.25, P=0.012). After treatment, the scores of FMA and ADL in the observation group were significantly higher than those in the control group ( t values were 9.23 and 9.54, respectively, P<0.01), the MAS and NIHSS scores were significantly lower than those in the control group ( t values were 10.23 and 11.97, respectively, P<0.01). After treatment, the distribution of patients in Brunnstrom stage Ⅴ and Ⅵand Holden functional walking stage Ⅳ and Ⅴ in the observation group was significantly higher than those in the control group ( χ2 values were 11.96 and 11.27, respectively, P<0.05). After treatment, APTT, PT and TT in the observation group were significantly longer than those in the control group ( t values were 10.37, 13.57 and 6.54, respectively, P<0.01); serum FIB, D-D and PAI-1 levels were significantly lower than those in the control group ( t values were 12.85, 11.94 and 27.39, respectively, P<0.01). No adverse reactions occurred in both groups. Conclusion:The treatment of post-stroke hemiplegia with Tongdu Tiaoshen acupuncture can improve the effect of clinical treatment and the ability of daily life, neurological function, limb function, movement and walking ability, and stabilize the clotting state.
8.The incidence and risk factors for hip fractures in elderly patients within two years after stroke onset
Xiaoqing DENG ; Yuqiu LUO ; Caikui WU ; Lixiang ZHANG ; Fang FANG ; Yanju FENG ; Zhicong CHEN ; Lihua HUANG ; Lixin XU ; Chunqiong LING ; Baojuan SHI ; Cailan WEI
Chinese Journal of Geriatrics 2020;39(2):159-163
Objective:To investigate the incidence, clinical characteristics and risk factors for hip fractures in patients within two years after stroke onset.Methods:A total of 332 persons with first-onset stroke from the neurology department of our hospital between 1 June 2013 and 31 December 2014 were recruited and were divided into the hip fracture group and the non-hip fracture group.Clinical characteristics were recorded.Vision was tested as normal or impaired.Patients were accessed by the National Institutes of Health Stroke Scale(NIHSS), Behavioral Inattention Test, Baking Tray Task, Mini-Mental State Examination(MMSE), Birgitta Lindmark(BL)motor assessment scale, Berg Balance Scale(BBS), Timed Up & Go(TUG)Scale, and Stops Walking When Talking(SWWT)Scale.The clinic characteristics and risk factors for hip fractures were compared between the two groups after a 2-year follow-up.The accuracy of risk factors for fracture prediction was assessed by the sensitivity, specificity, and positive and negative predictive values.Results:Of 332 patients with stroke, 16 cases fractured their hips within two years after stroke onset, which corresponded to an incidence of 33‰/year(95% CI: 15‰/year-50‰/year). The 2-year mortality rate was 44%(95% CI: 25%-60%)and 48%(95% CI: 42%-54%)in patients with and without hip fractures respectively( χ2=0.036, P=0.724). The mean survival time for patients with and without hip fracture was 2.72 years(95% CI: 1.45-2.79)and 2.21 years(95% CI: 1.48-2.34)respectively.The proportions of patients with previous fractures history( χ2=16.780, P=0.041)and impaired vision( χ2=11.210, P=0.027), MMSE scale score( U=14.220, P=0.031), TUG ≥ 15 s( χ2=18.560, P=0.000)were higher, and SWWT( χ2=20.340, P=0.000)was lower in the hip fracture group than in the non-hip fracture group.The negative predictive values of previous fractures history, impaired vision, TUG and SWWT were higher than their positive predictive value.The specificities of previous fractures history, impaired vision, and SWWT were higher than their sensitivities.And the sensitivity of TUG was higher than its specificity. Conclusions:Hip fractures after stroke are common in elderly patients.Fractures often occur during daytime at home in daily activities.The previous fractures history, visual and cognitive dysfunction and impaired functional mobility are risk factors for hip fractures.We should take measures to prevent falls according to the relevant factors.Among the test scales, the timed up & go(TUG)scale could much more accurately identify patients at high risk for hip fractures.
9.Clinical characteristics and risk factors for falls within two years after stroke in elderly patients
Yuqiu LUO ; Xiaoqing DENG ; Caikui WU ; Lixiang ZHANG ; Yanju FENG ; Zhicong CHEN ; Lihua HUANG ; Lixin XU ; Chunqiong LING ; Baojuan SHI ; Cailan WEI
Chinese Journal of Geriatrics 2018;37(9):978-983
Objective To examine the incidence ,clinical characteristics ,and risk factors for falls within two years after stroke in elderly patients. Methods A total of 365 elderly stroke patients from the Department of Neurology at the 8th Nanning People's Hospital were recruited from June 1 , 2013 to December 31 ,2014. They were divided into a fall group and a non-fall group and were followed up for two years. The incidence and clinic characteristics of falls were analyzed. The risk factors for falls were analyzed by multiple Logistic regression analysis. Results Of the 365 stroke patients included in this study ,falls were observed in 146(40.2% )patients. The interval between the stroke and the first fall :72(49.3% )patients had the first fall within 3 months;22(15.1% )occurred between 4 and 6 months;20 (13.7% )between 7 and 12 months ;17 (11.6% )between 13 and 18 months ;and 15 (10.3% )between 19 and 24 months.A hundred and five(71.9% )patients fell during daytime and 41 (28.1% )patients during night.Eighteen(12.3% )patients had one fall ;65(44.5% )patients fell 2 to 4 times ;60(41.1% )patients fell 5 to 10 times ;and 3(2.1% )patients fell over 10 times.A total of 709 falls were observed.Places of falls :102(69.9% )falls happened indoors and 44(30.1% )falls occurred outdoors.Circumstances of falls :27 (18.5% )patients fell when turning over ;23 (15.8% )fell when rising from a seating position ;4(2.7% )patients fell when showering ;15(10.3% )patients fell while standing ;9(6.8% )fell when turning around ;56(38.3% )fell while walking ;and 12(8.2% )fell while climbing the stairs or running.The severity of falls :52(35.6% )patients had no injury ;78(53.2% ) suffered soft tissue injury ;16 (11.0% )had fractures ;and 78 (53.2% )had fear of falling.Multiple Logistic regression analysis showed that age(OR=2.41 ;95% CI :1.69-3.05) ,history of falls(OR =2.85 ;95% CI :1.46-3.81) ,history of stroke(OR=1.87 ;95% CI :1.12-2.79) ,right hemiplegia(OR=2.37 ;95% CI :1.62-4.59) ,left hemiplegia(OR= 2.47 ;95% CI :1.46-4.78) ,paraplegia(OR= 2.55 ;95% CI :1.57-4.98) ,visual impairment(OR=2.35 ;95% CI :1.35-6.62) ,apraxia(OR=2.53 ;95% CI :1.42-5.63) ,unilateral spatial neglect (OR=3.34 ;95% CI :2.82-6.34) ,use of psychotropic medications (OR= 1.76 ;95% CI :1.11-1.98) ,impaired physical mobility (OR = 1.58 ;95% CI :1.82-2.91) ,low MMSE scale(OR = 3.42 ;95% CI :1.38-7.41) ,low Barthel Index score(OR = 2.83 ;95% CI :0.97-4.68) ,BBS scale<45(OR=2.48 ;95% CI :1.27-4.18) ,TUG>15seconds(OR=3.56 ;95% CI :1.91-5.23) ,and lack of rehabilitation therapy (OR=3.42 ;95% CI :1.38-7.41)were independent predictors for falls(all P<0.05). Conclusions Falls are common among elderly patients within two years after stroke.Most falls happen indoors ,during daytime and while moving.Age ,history of falls ,history of stroke ,hemiplegia ,visual impairment ,apraxia ,unilateral spatial neglect ,use of psychotropic medications ,walk with a walker ,low MMSE scale ,low Barthel Index score ,BBS scale<45 ,TUG>15 seconds ,and lack of rehabilitation therapy are independent risk factors for falls after stroke.
10.Research progress of real-time continuous glucose monitoring technology
Pei LUO ; Yanju HE ; Meixia LI ; Tingfeng WANG ; Lihua CHEN ; Ligang ZHOU
Clinical Medicine of China 2016;32(9):858-861
Objective Treatment of type 1 diabetes mellitus has always posed a challenge to balance hyperglycemia control with hypoglycemia episodes. This review attempts to outline the application and research progress of real?time continuous glucose monitoring technology.Given the evolution of RT?CGM technologies,it is likely that today’ s more accurate RT?CGM systems will result in improved patient trust and reduced alert fa?tigue,translating into more sustained RT?CGM use,greater use of the RT?CGM data,and better outcomes.

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