Objective To assess the disorders of glucose metabolism and insulin resistance in patients with rheumatoid arthritis (RA) and its relationship with disease activity.Methods One hundred and twenty-three RA patients along with 98 age and sex matched controls were studied.Seventy-five g oral glucose tolerance test was performed.The homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-β) were evaluated.Disease activity score (DAS28) was used to assess disease activity.According to their DAS28 values,patients were divided into high disease activity group and low to moderate disease activity group.Glucose tolerance and HOMA-IR were compared between the two groups.Parameters that reflects disease activity,such as CRP and ESR,as well as disease activity scores were compared between patients with T2DM or prediabetes and patients with normal glucose tolerance.The data was analyzed by t test,Pearson correlation analysis and chi-square test.Results The prevalence of T2DM [20.3％(25/123) vs 5.1％ (5/98),x2=10.774,P＜0.01] and prediabetes [39.0％ (48/123) vs 7.1％ (7/98),x2=29.657,P＜0.01] increased in RA patients compared to controls.RA patients had higher HOMA-IR (2.5±1.5 vs 0.8±0.4; t=5.185,P＜0.01) and lower HOMA-β (83±69 vs 192±85; t=3.768,P＜0.01) compared to controls.ESR [(55±30) mm/1 h vs (37±26) mm/1 h; t=3.159,P＜0.01],CRP [(40±23) mg/L vs (19±10) mg/L; t=3.628,P＜0.01] and DAS28 score (5.6±1.3 vs 4.8±1.2; t=2.923,P＜0.01) were higher in RA patients with T2DM or prediabetes than in RA patients with normal glucose tolerance.In RA patients,the HOMA-IR was significantly positively correlated with DAS28 (r=0.39,P＜0.01),ESR (r=0.54,P＜0.01)and CRP (r=0.20,P＜0.05).The HOMA-IR value and fasting insulin levels were higher in high disease activity patients (DAS28＞ 5.5) than in low-to-moderate disease activity patients (DAS28 ≤5.5) although fasting plasma glucose level did not differ significantly in these two groups.Conclusion The prevalence of T2DM and prediabetes increases in RA patients comparing to controls.RA patients have insulin resistance that is associated with disease activity and systemic inflammation.

Objective To compare the therapeutic effect of inhaled aerosolized and intravenous milrinone (a phosphodiesteraee-3 inhibitor) on postoperative pulmonary artery hypertension (PAH) in children with congenital heart disease (CHD).Methods Forty CHD complicated with PAH children aged 5-14 yr weighing 15-38 kg with pulmonary artery pressure (PAP) 30-90 mm Hg were randomly divided into 2 groups (n = 20 each): Ⅰ milrinone inhalation group and Ⅱ intravenous milrinone group. At the end of CPB, aerosolized milrinone 1 ml/kg was inhaled for 12 h at 30 min intervals, and each time milrinone was inhaled for 10 min in group Ⅰ . In group Ⅱ , a bolus of 10 g/kg milrinone was given iv followed by 12 h milrinone infusion at 0.5 μg·kg-1 ·min-1 . Blood samples were taken from aorta and pulmonary artery for blood gas analysis at the end of administration and venous oxygen saturation (S(-v)O2) was recorded. MAP, PAP, pulmonary vascular resistance index (PVRI) and systemic vascular resistance index (SVRI) were recorded every 2 h during milrinone administration. The duration of endotracheal tube, PAH, lung infection and postoperative hyoxemia were recorded during milrinone administration. Results PAP, PVRI and the incidence of lung infection and PAH were significantly lower, while MAP, SVRI and S(-v)O2higher in group Ⅰ than in group Ⅱ (P ＜ 0.05), but there was no significant difference in the duration of endotracheal tube and incidence of hyoxemia between the two groups(P ＞ 0.05). Conclusion Inhaled aerosolized milrinone has better therapeutic effect than intravenous milrinone on PAH in children with CHD.

OBJECTIVE: To explore the genetic basis of three children with unexplained developmental delay/intellectual disability (DD/ID). METHODS: Peripheral blood samples were collected from the patients and subjected to chromosomal microarray analysis (CMA). RESULTS: Patient 1 was found to harbor a 190 kb deletion at 9q34.3, which encompassed most of EHMT1 (OMIM 607001), the key gene for Kleefstra syndrome (OMIM 610253). Patients 2 and 3 were siblings. CMA showed that they have shared four chromosomal copy number variations (CNVs) including a deletion at 9q34.3 which spanned 154 kb and 149 kb, respectively, and encompassed the EHMT1 and CACNA1B (OMIM 601012) genes. The remaining 3 CNVs were predicted to be with no clinical significance. CONCLUSION Microdeletions at 9q33.4 probably underlay the pathogenesis of DD/ID in the three children, for which EHMT1 may be the key gene.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities/genetics* ; DNA Copy Number Variations ; Developmental Disabilities/genetics* ; Heart Defects, Congenital ; Humans ; Intellectual Disability/genetics*

OBJECTIVE: To verify a HLA-DQB1*03:90N allele and method to improve the accuracy of HLA typing. METHODS: A total of 2265 hematopoietic stem cell donors from Shenzhen Branch of China Marrow Donor Program in 2018 were initially detected by a PCR sequence-specific oligonucleotide probe (SSOP) method. Among these, a rare HLA-DQB1 allele was identified by sequence-based tying (SBT) and Ion Torrent S5 next generation sequencing (NGS). RESULTS: The SSOP typing result suggested the HLA-DQB1 to be a rare allele, while an insertion and a deletion was suspected in its exon 2 by SBT, which were confirmed by NGS as DQB1*03:90N and DQB1*06:01, respectively. CONCLUSION Rare alleles suspected by the SSOP method should be verified by other methods to ensure the accuracy of HLA genotyping. Rare alleles formed by deletions can be detected by NGS with accuracy.

Augmented renal clearance （ARC）refers to the significant enhancement of patients ’renal function ，which is manifested by the significant increase of glomerular filtration rate ，which increases the clearance of drugs ，and the effective blood drug concentration cannot be achieved under the conventional dose. The efficacy of antibiotics is closely related to the concentration. The influence of renal dysfunction on drug metabolism is an important factor that clinicians should consider when determining the dosage. This article reviews the definition ，risk factors ，occurrence mechanism ，evaluation methods of ARC ，as well as its impact on the pharmacokinetics/pharmacodynamics of antibiotics and administration methods. It is found that ARC widely exists in critically ill patients ，and the risk factors include age （≤50 years old ），brain trauma ，sepsis，multiple trauma ， etc. When using antibiotics in ARC patients ，the therapeutic effect of drugs can be improved by increasing the dosage ，prolonging the duration of administration and increasing the frequency of administration. However ，in order to prevent adverse reactions caused by high concentration accumulation of drugs ，it is recommended to try to combine treatment drug monitoring.

【Objective】 To study the frequency, Rh phenotypes and molecular & biological background of D-elute (D^el) phenotype in RhD-negative blood donors in Dalian. 【Methods】 A total of 355 serologically RhD-negative samples between November, 2018 and October, 2019 in Dalian Blood Center were collected, and tested for RhC, c, E, e phenotypes using monoclonal antibodies and anti-D adsorption/elution test. DNA was extracted by magnetic bead selection. RHD 1227G>A mutation was detected by melting curve analysis. All RHD exons were sequenced by Sanger sequencing. 【Results】 Among 355 serologically RhD-negative blood donors, 55 (15.5%) were identified as D^el and the remaining 300 cases (84.5%) were true RhD negative. Ccee (45/55, 81.8%) was the predominant Rh phenotype among 55 D^el cases while ccee (210/300, 70.0%) was the most prevalent Rh phenotypes in 300 true RhD negative cases. In 55 D^el cases, 51 (92.7%) had RHD 1227G>A mutation, and the other 4 cases(7.3%) had mutations in other sites. 【Conclusion】 The frequency of D^el was 15.5% in serologically RhD-negative blood donors in Dalian, with Ccee being the most prevalent Rh phenotype and RHD 1227G>A the most common gene mutation.

【Objective】 To establish an effective method for acquiring bone marrow-derived dendritic cells (DCs) from BALB/C mice in vitro and to establish a reservoir of DC precursor cells. 【Methods】 CD117⁺ hematopoietic stem cells (HSCs) were isolated and purified from bone marrow of BALB/C mice by immunomagnetic beads separation system (MACS), and then amplified in vitro with mouse stem cell factor (SCF) and interleukin-3 (IL-3). HSC was induced to differentiate into DCs by adding granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and IL-4. Different cytokines (tumor necrosis factor-alpha or IL-10) were added to control the maturity of dendritic cells. Then the morphology (electron microscopy), surface molecular markers (FACS method) and cytokine secretion level (ELISA method) were identified. 【Results】 ① The purity of CD117 ⁺ HSC isolated and purified by MACS system was over 95%. ② SCF plus IL-3 could effectively stimulate HSC amplification. ③ The morphology of mature DC (mDC) and immature DC (imDC) was significantly different under light and scanning electron microscopy. ④ In the expressions of surface markers CD40, CD80, CD86, I-A/I-E, there were significant differences between imDC group and mDC group (P<0.01). ⑤ After LPS stimulation, the secretion of IL-12 in imDC group did not change significantly (P=0.064), while the secretion of IL-12 in mDC group increased significantly (P=0.009). LPS and TNF-α had a synergistic effect in stimulating DC maturation. 【Conclusion】 Specific combinations of cytokines can effectively induce the differentiation of bone marrow HSCs into DCs in BALB/C mice, and can control the maturity of DCs. This study makes it possible to use gene modified dendritic cells in GD immunotherapy.