Objective To explore the associations of the genetic polymorphisms of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) with early-onset severe pre-eclampsia and the efficacy of labetalol therapy. Methods Totally 105 gravidas diagnosed with early-onset severe pre-eclampsia (experimental group) and 103 healthy gravidas (control group) were recruited from Beijing Obstetrics and Gynecology Hospital between August 2013 and July 2016. Labetalol was given to control blood pressures in gravidas with early-onset severe pre-eclampsia. If labetalol administration alone did not exceed the mean dose (100 mg, one dose per eight hours) and effectively controlled the blood pressures, it would be considered to be valid (n=75), otherwise it would be viewed as an invalid treatment. Genotype and allele frequencies of CYP2C9 gene (rs1057910 and rs4918758) and CYP2D6 gene (rs1065852, rs28371725, rs35742686 and rs3892097) in the gravidas were analyzed by TaqMan probe polymerase chain reaction. Differences in the genotype and allele frequencies were compared between the experimental and control groups, and the valid and invalid labetalol treatment groups. Chi-square test, analysis of variance and LSD test were used as statistical methods. Results The gravidas in both experimental and control groups were AA genotype in CYP2C9 gene rs1057910, TT genotype in CYP2D6 gene rs35742686 and CC genotype in CYP2D6 gene rs3892097. Frequencies of CC and CT genotypes in CYP2D6 gene rs28371725 in the experimental group were higher than those in the control group [18.1% (19/105) vs 14.6% (15/103);56.2% (59/105) vs 42.7% (44/103); χ2=6.707], and higher C allele frequency in CYP2D6 gene rs28371725 was also observed in the experimental group [46.2% (97/210) vs 35.9% (74/206), χ2=4.529] (all P<0.05). No statistical differences in maternal age, diastolic pressure, body mass index before pregnancy, serum triglyceride, creatinine and neonatal birth weight were observed among women with CC, CT or TT genotype of CYP2D6 gene rs28371725 in the experimental group (all P>0.05). Compared with the gravidas with CT or TT genotype of CYP2D6 gene rs28371725, those with CC genotype had longer gestational age [(32.5±2.1) vs (29.5±1.8) and (29.8±2.2) weeks] and higher plasma albumin [(27.2±9.3) vs (20.3±10.4) and (22.5±7.4) g/L], but lower systolic pressure and 24 hours urine protein (LSD test, all P<0.05). The G allele frequency in CYP2D6 gene rs1065852 in invalid labetalol treatment group was higher than that in valid labetalol treatment group [93.3% (56/60) vs 76.0% (114/150), χ2=8.351, P=0.004]. Conclusions The polymorphism of CYP2D6 gene rs28371725 may be associated with early-onset severe pre-eclampsia, and the allele of G in CYP2D6 gene rs1065852 may be associated with the efficacy of labetalol in treatment of early-onset severe pre-eclampsia.

Objective To discuss protein marks expressed differentially in placenta of Down's syndrome by means of proteomics. Methods We collected placenta of 18 patients(from March 2009 to December 2009 at Beijing Obstetrics and Gynecology Hospital), and divided them into two groups, one was 10 patients with fetal Down's syndrome, the other was normal pregnancies (normal chromosome) with other diseases. We separated proteins expressed in placentas of two groups by two-dimensional difference gel electrophoresis (2D-DIGE), and then analyzed the differential protein spots by software Decyder 6. 5, then,spots differentially expressed by 1.5 fold or more were analyzed by matrix assisted laser desorption ionizationtime of flight-mass spectrometry (MALDI-TOF-MS). In the end, the differential expressional levels of partially identified proteins were validated by western blot analysis. Results (1) Differential proteins of two groups protein spots of placentas separated by 2D-DIGE were analyzed by software Decyder 6. 5 (these colored lights scattered in the image were protein spots), a total of 56 spots out of 352 were differentially expressed (P<0. 05) in two groups. We analyzed 17 protein spots(12 protein spots were over-expressed and 5 protein spots were down-expressed) differentially expressed by 1.5 fold or more by MALDI-TOF-MS.(2) Protein matching after searching protein database, 17 protein spots turn out to be 10 proteins. Four kinds [superoxide dismutase 1 (SOD1), peroxiredoxin 6 (PRDX6), heat shock protein 27 (HSP27),endoplasmic reticulum protein 29 (ERP29)] of them were validated by western blot analysis, the group of fetal Down's syndrome were 0.74 ±0. 12,0.29 ±0. 10,0.53 ±0. 16,0.20 ±0. 09,the group of normal pregnancies were 0. 51 ±0. 08,0. 34 ± 0. 16,0. 18 ± 0. 07,0. 35 ± 0. 09, the results confirmed the observed changes in proteomics. Conclusions Compared with normal pregnancies, there were differential proteins expressed in placenta of Down's syndrome. This approach might provide new screening markers in use for prediction of Down's syndrome, however, further study should be done to make these 4 proteins (SOD1,HSP27, ERP29, PRDX6) be new screening markers.

Objective To investigate genes involved in the mechanisms underlying the progression of severe preeclampsia.Methods We conducted a muhiregional gene expression analysis using peripheral leucocytes from patients with preeclampsia and normal controls.Total RNA was extracted from peripheral blood of six severe preeclampsia and five normotensive pregnancies.We performed genome-wide expression profiling using Affymetrix HG_U133 plus 2.0 chips to screen out differentially expressed genes of 2 fold or more and q_value ＜ 5.4%.Using Gene Ontology we identified the function of differentially expressed genes after cluster analysis.Results Among the 47 000 genes that were screened in the microarray,140 genes were found to be differentially expressed between normal and preeclamptic pregnancies. Eighty six up-regulated candidate genes were mainly involved in cysteine metabolism urea cycle and metabolism of amiogroups,proteasome,TGF-beta signaling pathway, and the ratio of calponin2 (CNN2), matrix metallopeptidase 8 (MMP8),V-set and immunoglobulin domain containing 4 (VSIG4),proteasome 26S subunit ATPase 5 (PSMC5) was evidently increased in preeclampsia patients.Among 54 down-regulatedcandidates,natural killer cell mediated cytotoxicity,antigen processing and presentation,metabolism of xenobiotics by cytochrome P450 were the main pathways.KIR3DL2,AKR1C3,CHURC1 and SLC25A13 were obviously decreased in preeclampsia patients. Conclusions The gene expression of peripheral leucocytes in preeclampsia patients is significantly different from that of uncomplicated pregnancies.CNN2,MMP8,VSIG4,PSMC5,KIR3DL2,AKR1C3,CHURC1 and SLC25A13 may be involved in the molecular mechanisms underlying the progression of severe preeclampsia.

Objective:To compare the concordance between subjective experience and clinician-rated in different treatment phrase of elderly patients with depressive disorder,and to explore the relevant factors.Methods:Sixty-nine consecutive elderly patiems with depressive disorder diagnosed with International Classification of Diseases-10 criteria were included.The Visual Scale for Depression(VSD) were used to evaluate subjective experience of depression,while the Hamilton Depression Scale (HAMD),Hamilton Anxiety Scale (HAMA),Minimum Mental State Examination (MMSE) were used by clinician to evaluate depression symptom,anxiety symptom and cognition at baseline,2-,4-and 52-week of the treatment respectively.Results:Compared with baseline,VSD scores were increased at 2 weeks and 4 weeks [(2.7 ± 1.6),(5.3 ± 2.0) vs.(7.0 ± 1.8),P ＜ 0.001],HAMD scores were decreased at 2 weeks and 4 weeks [(36 ± 11),(17 ±9) vs.(9 ±8),P ＜0.001],HAMA scores were decreased at 2 weeks and 4 weeks [(27 ± 10),(14 ±8) vs.(7 ±6),P ＜0.001].No significant differences were found between 4 weeks and 52 weeks.There was no correlation between VSD and HAMD scores at baseline and 2 weeks.There were significant correlations among scores of VSD and HAMD(r =-0.31,-0.74,Ps ＜ 0.05),HAMA (r =-0.36,-0.76,Ps ＜ 0.05) at 4 weeks and 52 weeks.Using logistic regression analysis,the concordance between VSD and HAMD related with the factors of HAMD,higher scores of anxiety/somatization factor were associated with lower concordance (OR =0.87),and higher scores of weight factor (OR =1.86),diurnal variation factor (OR =2.00),hopelessness factor (OR =1.13) were associated with higher concordance.Conclusion:Compared with acute depression phase,concordance between subjective experience and clinician-rated for depression may be higher at depression remission phase in elderly patients with depression,which suggests that characteristics of depression symptom may have a certain impact on the self-awareness for depression experience.

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39⁺CD73⁺ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A_2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6C^hi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF⁺CD4⁺ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.