Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis.@*METHODS@#A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared.@*RESULTS@#The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively.@*CONCLUSION@#Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Efficacy of sublingual immunotherapy with dermatophagoides farinae drops in monosensitized and polysensitized patients with allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To compare the efficacy of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farinae drops in monosensitized and polysensitized patients with allergic rhinitis.</p><p><b>METHODS</b>The efficacy of SLIT in 69 patients who were sensitized to house dust mites and treated with Dermatophagoides farinae drops for 1.5-2.0 year with complete clinical data were analyzed retrospectively. These patients had been divided into the monoallergen sensitized group and polyallergen sensitized group according to the results of skin prick tests. The total medication score (TMS) and the total nasal symptoms score (TNSS) were evaluated before and half an year, 1.0 year and 1.5-2.0 years after SLIT treatment.</p><p><b>RESULTS</b>After SLIT treatment for half an year, the TNSS in the monoallergen sensitized group (2.00 [1.00; 3.00]) was significantly lower than that in the polyallergen sensitized group (3.00 [2.00; 4.00], Z = -2.851, P < 0.05), this significant difference of TNSS between the two groups was also found after SLIT treatment for 1.0 year (0.00 [0.00; 1.00], 2.00 [0.00; 3.00], Z = -2.590, P < 0.05). Whereas, there was no significant difference between the two groups after 1.5-2.0 years treatment refer to the TNSS (0.00 [0.00; 1.00], 0.00 [0. 00; 2.00], Z = -1.461, P > 0.05). Half an year, 1.0 year and 1.5-2.0 years after SLIT treatment, the TMS in both groups reduced significantly, with no significant difference between two groups (Z value was - 0.777, -0.944, -0.907, all P > 0. 05).</p><p><b>CONCLUSIONS</b>SLIT with Dermatophagoides farinae drops is effective in monosensitized and polysensitized patients with allergic rhinitis. And equivalent efficacy could be achieved after 1.5-2.years.</p>

Protection role of silent information regulator 1 in toxicity of activated BV-2 cells to PC12 cells / 中华神经医学杂志

Objective To observe the effects of silent information regulator 1 (SIRT1) on toxicity of activated BV-2 to PC12 cells and the possible mechanisms.Methods BV-2 microglial cells and PC12 cells were routinely cultured in vitro; ELISA was used to measure to the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) stimulated by lipopolysaccharide (LPS,1 μg/mL) in BV-2 cells.MTT assay was employed to identify the cell viability of PC12 cells injured by culture medium of activated BV-2 and determined the suitable concentrations of resveratrol (a potent SIRT1 activator,5,10,25,50 and 100 μmol/L) and nicotinamide (a known SIRT1 inhibitor,5,10,25 and 50 mmol/L).PC12 cells were divided into groups as follows:control group Ⅱ,LPS+BV-2 co-cultured group,resveratrol treatment group and nicotinamide treatment group (pretreated with resveratrol or nicotinamide for 2 h,and then subjected to culture medium of activated BV-2 cells,in the presence of resveratrol or sirtinol for 18 h); the cell viability was measured by OD value in MTT assay,and the expressions of SIRT1 and acetyl-p53 were detected by Western blotting.Results TNF-α and IL-6 secretions increased gradually at 6,12 and 24 h after LPS being induced BV-2,with significant difference between each two time points (P＜0.05).PC12 cell viability decreased in the LPS+BV-2 co-cultured group as compared with that in the control group Ⅰ,LPS treatment group and BV-2 supernate group (P＜0.05).The cell viability of cells in the 100 μmol/L resveratrol treatment group and 50 μmol/L niacinamide treatment group decreased as compared with that in the control group Ⅱ (P＜0.05),therefore,50 μmol/L resveratrol and 25 μmol/L nicotinamide were chosen in the next experiment.As compared with those in the control group Ⅲ,the cell viability and SIRT1 expression significantly decreased,and acetyl-p53expression significantly increased in the LPS+BV-2 co-cultured group (P＜0.05); as compared with those in the in the LPS+BV-2 co-cultured group,the cell viability and SIRT1 expression significantly increased,and acetyl-p53 expression significantly decreased in the 50 μmol/L resveratrol treatment group,and opposite results were noted in the 25 μmol/L nicotinamide treatment group (P＜0.05).Conclusion SIRT1 can inhibit toxicity of activated BV-2 to PC12 cells,the mechanism of which is partly via p53 activation.

Role of silence information regulator 1 in regulation of lipopolysaccharide-induced secretion of interleukin-6 and tumor necrosis factor-a in activated BV-2 cells / 中华神经医学杂志

Objective To observe the effect oflipopolysaccharide (LPS) on the cell form of BV-2 cells and the expressions of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) so as to detect the role of silence information regulator 1 (SIRT1) in regulation of LPS-induced proinflammatory cytokines production in activated BV-2 cells.Methods BV-2 cells were divided into control group (normal culture medium) and treatment groups; BV-2 cells in the treatment groups were subdivided into LPS treatment groups,Resveratrol+LPS treatment groups and Sirtinol+LPS treatment groups (cultured with different concentrations of LPS,SIRT1 activator Resveratrol or SIRT1 inhibitor Sirtinol,respectively).MTT assay was employed to identify the cell survival after the inducement.Based on the above MTT results,the cells were then grouped into the control group,LPS treatment group,Resveratrol+LPS treatment group and Sirtinol+LPS treatment group having suitable concentrations of LPS,Resveratrol and Sirtinol; then,the levels of IL-6 and TNF-a were measured with enzyme-linked immuno sorbent assay (ELISA) at 12 and 24 h after the inducement; and the expression of SIRT1 at 24 hafter the inducement was detected by Western blotting.Results As compared with those in the control group,the BV-2 cells in the LPS treatment group had increased cell number,hypertrophic cell body,and shorten cell processes.The cell survival rate increased with increased concentrations of LPS.As compared with those in the control group,the levels of IL-6 and TNF-a in LPS treatment group increased and level of SIRT 1 decreased with significant differences (P＜0.05).Significantly increased levels of IL-6and TNF-a and obviously decreased expression of SIRT1 in the Resveratrol+LPS treatment group were noted as compared with those in the LPS treatment group (P＜0.05); conversely,significantly decreased levels of IL-6 and TNF-a and obviously increased expression of SIRT1 in the Sirtinol+LPS treatment group were noted as compared with those in the LPS treatment group (P＜0.05).Conclusion LPS can change the morphology of BV-2 cells,and induce the levels ofproinflammatory cytokines; impairment of SIRT1 may contribute to such progress obviously.

Cilostazol inhibits expression of P38 mitogen-activated protein kinase and proliferation of human vascular endothelial cells / 中华神经医学杂志

Objective To observe the effect ofcilostazol(CLZ)on proliferation of human vein endothelial cells(VECs)in vitro and activity ofphosphorylation P38 mitogen-activated protein kinase (MAPK).Methods Human umbilical vein endothelial cell(HUVEC)line EA.hy926 culturedin vitro was treated with CLZ at concentrations of 10,30,100 and 300 μmo/L for 24 h; blank controls were also employed.The ratio of cell proliferation was determined by MTT assay; the protein expression of phosphorylation P38MAPK was evaluated by Western blotting.Results The proliferation ratio(A value)of HUVECs was(0.909±0.013)in the control group,and(0.903 ±0.026),(0.851 ±0.023),(0.699±0.013),and(0.651±0.036)in the 10,30,100 and 300 μno/L CLZ-treatment groups,respectively; as compared with that in the blank control group,the A value in the 30,100 and 300 μmo/L CLZ-treatment groups was significantly lower(P＜0.05); and a decreased trend at dose-dependent manner was noted among the 30,100 and 300 μno/L CLZ-treatment groups.As compared with that in the control group,the protein expression of phosphorylation P38MAPK in the 30,100 and 300 μmo/L CLZ-treatment groups was significantly decreased(P＜0.05),and the protein expression of phosphorylation P38MAPK in 300 μmo/L CLZ-treatment group was significantly lower than that in 30 μno/L CLZ-treatment group (P＜0.05).Conclusion CLZ can obviously inhibit the protein expression of P38MAPK and in vitro proliferation of VECs.

Proteomics of epilepsy induced by focal disorder of cortical development / 中华神经医学杂志

Objective To explore the proteomics of epilepsy induced by focal disorder of cortical development (DCD) in revealing the molecular mechanisms of epilepsy caused by DCD and looking for the candidate targets and new therapeutic approaches in clinical practice. Methods Animal models of DCD were established and induced by liquid nitrogen in healthy Wistar newborn rats. Animal model of DCD were divided into epilepsy group and control group according to Racine classification. The proteomics maps of the frontal cortex were obtained in the epilepsy group and the control group by two-dimensional electrophoresis and both Coomassie brilliant blue G250 and silver dying. The proteomics profiles of frontal cortex were preliminary analyzed with PD Quest 7.3 analysis package. The differentially expressed protein spots were excised from gel and digested with trypsin under optimal conditions. The masses of tryptic-digested peptides were acquired with a Voyager DA-STR matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometer. The acquired monoisotopic masses of analyzed proteins were matched in silico with theoretical peptide masses of human protein in the swiss-prot database with a mass tolerance of less than 50 ppm. Results One hundred and three proteins of differential expression were observed in the frontal cortex tissues of epilepsy associated with disorder of cortical development in rats, in which 64 were detected to be up-regulated and 39 were down-regulated. Finally, 12 proteins were identified as Lissencephaly-1 protein, synaptotagmin Ⅳ, Glial fibrillary acidic protein, HSP70, growth associated protein 43, neuronal enolase, tubulin beta chain, glutamine synthetase, neuron cytoplasmic protein, voltage-dependent anion channel proteins 1, pyruvate kinase and neurofilament light polypeptide. Conclusion These proteins may play pivotal roles in the pathogenic mechanisms of epilepsy caused by disorder of cortical development and may provide new therapeutic targets for refractory epilepsy in the future.

Comparison of urinary proteomics between steroid-sensitive and steroid-resistant minimal change nephrotic syndrome in children / 南方医科大学学报

<p><b>OBJECTIVE</b>To screen the differentially expressed proteins in the urine of children with steroid-sensitive and steroid-resistant minimal change nephrotic syndrome (SRINS and SSINS, respectively).</p><p><b>METHODS</b>Urine samples were collected from 10 children with SRINS and 70 with SSINS as well as 30 healthy volunteers (control). Isoelectric focusing and two-dimensional electrophoresis in combination with matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry was performed for analysis of the urine proteins.</p><p><b>RESULTS AND CONCLUSION</b>In the urine samples, 30 protein spots were identified to have differential expression between SRINS and SSINS. Further analysis of 14 protein spots identified 12 proteins expressing in SRINS, namely kinesin family member 27, PITPNB, bullous pemphigoid antigen, alpha-1 protease inhibitor, Zn-alpha-2GP, alpha-1B-glycoprotein, serum albumin precursor, haptoglobin precursor, kinesin like motor protein, IRAK4, cytoplasmic dynein and cytokeratin 9. Nine of these 12 proteins were up-regulated (U1-U3, U5, U7-U9, U11-U12) and 3 down-regulated (D4, D6, D10) in SRINS, suggesting that these proteins may serve as the potential therapeutic targets and as new diagnostic markers for steroid-resistant nephrotic syndrome.</p>

Association of Interleukin-1?-511C/T and Interleukin-1?+3953C/T Polymorphisms with Susceptibility of Pediatric Epilepsy / 实用儿科临床杂志

Objective To explore the relationship between IL-1?-511C/T and IL-1?+3953C/T site polymorphisms and the susceptibility of pediatric epilepsy.Methods Under the case-control study,IL-1?-511C/T and IL-1?+3953C/T site polymorphisms in 117 patients with pediatric epilepsy and 95 healthy individuals controls(healthy control group) were analyzed with polymerase chain reaction restriction and fragment length polymorphism(PCR-RFLP),the relationship between IL-1?-511C/T,IL-1?+3953 C/T site polymorphisms and the risk of pediatric epilepsy were analyzed.SAS 8.0 software was used to analyze the data.Results Multiple variate logistic regression analysis revealed that compared with healthy control group,there was no relationship between the IL-1?-511C/T site polymorphisms and the susceptibility of pediatric epilepsy individuals,carrying at least one +3953T variant allele(CT and TT genotypes) had a significantly increased risk for pediatric epilepsy(adjusted OR=2.46,95%CI 1.03-5.87),compared with the wild-type genotype(+3953CC).Furthermore,individuals with epilepsy or febrile seizures family history had a significantly higher risk(adjusted OR=4.12,95%CI 1.28-29.34),compared with those with both CC genotypes.Conclusions These findings support the hypothesis that IL-1?-511C/T site polymorphisms have no relationship with epilepsy,but the IL-1?+3953C/T polymorphism may contribute to the risk of developing pediatric epilepsy.

Perinatal outcomes of 45 pregnant women with pulmonary hypertension complicating congenital heart disease / 中华妇产科杂志

Objective To explore the perinatal outcomes of women with pulmonary hypertension complicating congenital heart disease(CHD).Methods Clinical data of 45 cases of pregnant women with pulmonary hypertension complicating CHD from Apr 1995 to May 2007 were analyzed and they were divided into three groups:29 cases of slight group[pulmonary hypertension of 30 mm Hg(1 mm Hg=0.133 kPa) to 49 mm Hg],8 cases of moderate group(pulmonary hypertension of 50 mm Hg to 79 mm Hg)and 8 cases of severe group(pulmonary hypertension equal to or higher than 80 mm Hg).The types of CHD,cardiac functional status(New York heart association,NYHA),gestational weeks of pregnancy termination,mode of delivery,pregnancy after CHD operation and outcomes of infants were compared between the groups. Results(1)The highest incidence of CHD were atrial septal defect and ventricular septal defect(58%, 26/45).The rate of pregnant women after CHD operation was 29%(13/45),they were mainly in slight group and their NYHA class were in Ⅰ-Ⅱ.(2)The occurrence rate of NYHA class Ⅲ-Ⅳ was 7/8 in severe group.The rate of NYHA class Ⅰ-Ⅱ as 6/8 in moderate group.The rate of NYHA class Ⅰ- was 97%(28 /29)in slight group.(3)The rate of term delivery was 93%(27/29),preterm labor 3% (1/29),abortion 3%(1/29),and the birth weight was(3153?399)g on average in slight group.The rate of term delivery was 5/8,preterm labor occurred in 3 cases in moderate group.The rate of term delivery was 5/8,preterm labor occurred in 2 cases,and iatrogenic abortion in 1 case in severe group.The average birth weight between slight group and moderate or severe group had a significant difference.(4)Caesarean section rate was 78 %(35/45)among all patients.The rate of cesarean section delivery was 76%(22/29)in slight group,6/8 in moderate group,and 7/8 in severe group.(5)The rate of pregnant women who had portent heart failure or heart failure was 24%(11/45),overall maternal mortality was 4%(2/45).Conclusions The higher the pulmonary hypertension,the worse the outcome of the mother and fetus;The pregnant women with good heart function after cardiac operation would have a good perinatal outcome.Cesarean section is more suitable for those women.