Mean corpuscular volume ≤100 fl was an independent prognostic factor in patients with myelodysplastic syndrome and bone marrow blast<5 percent / 中华血液学杂志

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion: MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.

Clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes / 中华血液学杂志

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ(2)=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion: TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.

A study of clinical characteristics and prognosis of primary myelofibrosis patients with thrombocytopenia in varied degrees / 中华血液学杂志

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion: PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

23-Gauge pars plana vitrectomy and scleral buckle for the treatment of proliferative rhegmatogenous retinal detachment with inferior breaks / 眼科新进展

Objective To compare the safety and efficacy of 23-Gauge pars plana vitrectomy (PPV) and PPV combined with scleral buckling-PPV (SB-PPV) in proliferative rhegmatogenous retinal detachments with inferior breaks.Methods Retrospectively nonrandomized clinical case study was conducted in 70 patients with proliferative rhegmatogenous retinal detachment associated with inferior breaks between January 2013 and December 2016,including 39 eyes receiving SB-PPV procedures as the SB-PPV group and 31 eyes undergoing PPV procedures as the PPV group.And anatomical success rate for one procedure,lens trauma rate,retinotomy rate,postoperative best corrected visual acuity (BCVA) outcome and intraocular pressure (IOP) were recorded and analyzed.Results The anatomical success rate for one procedure was 92.3％ (36/ 39) in the SB-PPV group and 74.2％ (23/31) in the PPV group,and the difference was statistically significant (P ＜ 0.035).The lens trauma rate was 2.6％ (1/39) in the SB-PPV group and 19.4％ (6/31) in PPV group,with the difference being statistically significant (P ＜0.05).The retinotomy rate was 5.1％ (2/39) in the SB-PPV group and 32.3％ (10/31) in the PPV group,and the difference approached statistically significance (P ＜0.05).There was no significant difference in the postoperative BCVA and IOP between the two groups (both P ＞ 0.05).Conclusion SB-PPV can increase the anatomical success rate for one procedure in patients with rhegmatogenous retinal detachment associated with inferior breaks,and reduce retinotomy rate and lens trauma rate.

Correlation between end-tidal carbon dioxide and partial pressure of arterial carbon dioxide in ventilated newborns / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the correlation between end-tidal carbon dioxide (PetCO2) and partial pressure of arterial carbon dioxide (PaCO2) in ventilated newborns.</p><p><b>METHODS</b>Thirty-one ventilated newborn underwent mainstream PetCO2 monitoring; meanwhile, arterial blood gas analysis was performed. The correlation and consistency between PetCO2 and PaCO2 were assessed.</p><p><b>RESULTS</b>A total of 85 end-tidal and arterial CO2 pairs were obtained from 31 ventilated newborns. The mean PetCO2 (41±10 mm Hg) was significantly lower than the corresponding mean PaCO2 (46±11 mm Hg) (P<0.01). There was a significant positive correlation between PetCO2 and PaCO2 (r=0.92, P<0.01). The overall PetCO2 bias was 5.1±4.3 mm Hg (95% limits of consistency, -3.3 to 13.6 mmHg), and 5% (4/85) of the points were beyond the 95%CI. When the oxygenation index (OI) was less than 300 mm Hg (n=48), there was a significant positive correlation between PetCO2 and PaCO2 (r=0.85, P<0.01); the PetCO2 bias was 5.9±4.3 mm Hg (95% limits of consistency, -2.6 to 14.5 mm Hg), and 4.2% (2/48) of the points were beyond the 95%CI. When the OI was more than 300 mm Hg (n=37), there was also a significant positive correlation between PetCO2 and PaCO2 (r=0.91, P<0.01); the PetCO2 bias was 4.1±4.1 mm Hg (95% limits of consistency, -3.9 to 12.1 mm Hg), and 5% (2/37) of the points were beyond the 95%CI.</p><p><b>CONCLUSIONS</b>There is a good correlation and consistency between PetCO2 and PaCO2 in ventilated newborns.</p>

Role of Th17 cell and CD4+CD25+ regulatory T cells in inflammatory response in neonatal sepsis / 中华实用儿科临床杂志

Objective To investigate the roles of Thl7 cells and CD4 + CD25 + regulatory T cells in inflammatory response in neonatal sepsis.Methods Twenty children with neonatal sepsis (neonatal sepsis group) and 16 healthy neonates (healthy control group)were studied.Flow cytometric analysis (FCM) was performed to detect the percentage of CD4 + CD25 + Treg cells subpopulation.Real-time transcription-polymerase chain reaction (Real-time PCR) was used to analyze interleukin-17A (IL-17A),IL-17F,the transcription factor retinoid-related orphan nuclear receptor γt (ROR-γt),the forkhead/winged-helix protein 3 (Foxp3) and cytokines IL-6,transforming growth factor beta (TGF-β) expression in CD4 + T cell.Expressions of proinflammatory cytokines [IL-1β,IL-6,IL-10,tumor necrosis factor α (TNF-α)] were measured by using enzyme-linked immunosorbent serologic assay.Results Compared with healthy control group:1.The proportions of CD4 + CD25 + Treg cells in neonatal sepsis group were significantly higher [(15.33 ± 2.68) ％ vs (2.96 ± 0.56) ％,P ＜ 0.01].The mRNA expression of transcription factor Foxp3 in neonatal sepsis group showed similar tendency[(42.76 ± 10.83) × 10-4 vs (22.34 ±4.17) × 10-4,P ＜0.01].2.Expression levels of IL-17A and IL-17F were significantly up-regulated in neonatal sepsis group[IL-17A:(13.56 ±3.21) × 10-6 vs (4.76 ±1.39) ×10-6,P＜0.01 ;IL-17F:(7.62 ±1.45) ×10-4 vs (1.89 ±0.48) ×10-4,P＜0.01] and the expression levels of the transcription factor ROR-γt in CD4 + T cells were significantly increased in neonatal sepsis group [(9.22 ± 1.79) × 10-5 vs (2.84 ±0.56) × 10-5,P ＜0.01].3.Expressions of proinflammatory cytokines (IL-1β,IL-6,IL-8,TNF-α) in neonatal sepsis group were higher than those in control group [IL-1β:(2977.36 ± 653.97) pg/L vs (480.52 ± 120.36) pg/L,P ＜ 0.01 ; IL-6:(3143.82 ± 775.08) pg/L vs (393.78 ± 96.55) pg/L,P ＜ 0.01) ; IL-10:(3216.98 ± 678.43) pg/L vs (326.11 ± 62.45) pg/L,P ＜ 0.01 ; TNF-α:(3582.24 ± 876.13) pg/L vs (1233.68 ± 289.39) pg/L,P ＜ 0.01].Conclusion Aberrant activation of Th17 cell and CD4 + CD25 + Treg cell might be involved in pathogenesis in neonatal sepsis.

Correlation between mannose-binding lectin gene codon 54 polymorphism and susceptibility of Kawasaki disease / 中华儿科杂志

<p><b>OBJECTIVE</b>Human mannose-binding lectin (MBL) is a C-type serum lectin synthesized by the liver as an acute-phase protein. MBL can bind to glycoproteins terminated with mannose and N-acetylglucosamine present in the cell walls on a variety of microorganisms. Therefore, MBL appears to play an important role in the immune system. Low levels of MBL in human have been associated with a susceptibility to recurrent infections. MBL deficiency and low serum MBL levels are strongly associated with the presence of three point mutations at codon 52, 54 and 57 of exon 1 in the human MBL gene, and in Chinese population, the codon-54 mutation occurs at a frequency of 0.11 - 0.17. The data suggested that MBL insufficiency might also predispose to the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The possibility that Kawasaki disease (KD) is an infectious disease has been discussed and investigated for decades, in light of the implication that infections are involved in the pathogenesis of KD. It has been suggested that MBL insufficiency might predispose to the occurrence of KD. This study was aimed to investigate the genetic association of MBL codon-54 polymorphism in patients with KD, and to investigate possible associations with clinical manifestations of the disease.</p><p><b>METHODS</b>There were 95 patients with KD and 160 healthy subjects in the study. The genotype of MBL gene 54 codon was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical characteristics and biochemical examination were also performed.</p><p><b>RESULTS</b>The genotype frequency of heterozygote (GGC/GAC) was significantly higher in KD group than that in healthy subjects (45.2% vs 25.0%, P < 0.01), and the allele frequency of GAC mutation was also higher in KD patients than that in control group (0.258 vs 0.138, P < 0.01). The variant allele (GAC) was markedly associated with KD (OR = 2.18, 95% CI = 1.38 approximately 3.44, P < 0.05). But there was no significant difference in the allele frequency of GAC between patients with and without coronary artery lesion (CAL) in KD cases (0.281 vs 0.246, P > 0.05). In addition, in cases of KD, more patients carrying the variant allele (GAC) had episodes of upper respiratory or gastrointestinal infections prior to the onset of KD than wild homozygotes (P < 0.01).</p><p><b>CONCLUSION</b>The codon 54 polymorphism of MBL gene was associated with KD. It is possible that MBL gene codon 54 mutation might be related to the pathogenesis of KD.</p>

The correlation between Kawasaki disease and polymorphisms of Tumor necrosis factor alpha and interleukin-10 gene promoter / 中华儿科杂志

<p><b>OBJECTIVE</b>Kawasaki disease (KD) is an acute febrile vasculitic syndrome of unknown etiology that preferentially affects coronary artery. It has been suggested that proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) are key players during acute KD. Recently, the polymorphisms relative to major transcriptional start site of TNF-alpha and IL-10 gene were shown to influence the level of TNF-alpha and IL-10 production in vitro. This study was aimed to investigate the genetic association of TNF-alpha and IL-10 promoter polymorphisms in juvenile patients of Han nationality with KD, and to investigate the possible associations with clinical manifestations of the disease.</p><p><b>METHODS</b>Four polymorphism sites of TNF-alpha and IL-10 gene promoter regions from 96 children with KD were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). One hundred and sixty age-matched normal children of the Han nationality were used as control. All patients accepted Doppler echocardiography examination in order to differentiate coronary artery lesions.</p><p><b>RESULTS</b>There was significant difference in allele frequencies of -308 (A/G) site of the TNF-alpha gene between children of the Han nationality and those of Japanese and Caucasian in America. There were significant differences in the allele frequencies of -1082 (G/A), -819 (C/T) and -592 (A/C) of IL-10 gene between children of the Han nationality and their British Counterparts (P < 0.01). There was no significant difference in allele frequencies of -308 (A/G) site of TNF-alpha gene between children with KD and normal controls. There was no significant difference in the haplotypes and the allele frequencies of the above three sites of IL-10 between the two groups. However, when clinical features were examined, the genotype frequency of TNF-alpha-308A was significantly higher in IVIG-resistant KD patients than that of TNF-alpha-308G genotype (67% vs 5%, chi(c)(2) = 90.48, P < 0.01). The genotype of TNF-alpha-308A was closely associated with IVIG-resistant KD (P < 0.01, relative risk 42.25, 95% confidence interval 15.81-112.88). The haplotype frequency of IL-10 -1082A/-819T/-592A was also higher in patients with coronary artery lesion (CAL) caused by KD than those of Non-ATA haplotype (52% vs 20%, chi(2) = 18.36, P < 0.01). The haplotypes of IL-10 -1082A/-819T/-592A was significantly associated with CAL caused by KD (P < 0.01, relative risk 4.26, 95% confidence interval 2.20-8.25).</p><p><b>CONCLUSION</b>The genotype of TNF-alpha-308A is one of the important factors that probably influence the therapeutic effect of KD. The haplotypes (-1082/-819/-592) of IL-10 gene promoter might be related to the pathogenesis of coronary artery complication of KD and -1082A/-819T/-592A haplotypes might be regarded as a genetic marker of risk factor for coronary artery lesion in KD.</p>