ObjectiveTo investigate the expression of diabetes related microRNA （miRNA） in plasma exosomes of pregnant women complicated with gestational diabetes mellitus （GDM） and to study their association with the pathogenesis of GDM. MethodsIn this study， diabetes related miRNAs microarray data sets were searched through Gene Expression Omnibus （GEO） database， and screened by GEO2R to determine the candidate miRNAs. Differentially expressed miRNAs were selected if the change is consistent in more than one microarray data sets. Singleton pregnant women within 10-16 gestational weeks （gws） were included and their plasma was obtained for further analysis. In 24~28 gws， oral glucose tolerance tests （OGTT） were performed to diagnose GDM or normal glucose tolerance （NGT）. Diabetes related miRNAs expression in plasmatic exosomes was compared between GDM and NGT groups by RT-PCR. Receiver operating characteristic （ROC） curve was applied to assess the predictive efficiency of miRNAs. Finally， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis was used to reveal the function of miRNAs. ResultsFive diabetes related microarray datasets were downloaded from GEO database， including GSE94649， GSE21321， GSE98043， GSE148961 and GSE27645. Ten differentially expressed miRNAs were found， among which seven were up-regulated and three were down-regulated. RT-PCR results showed that， compared with NGT group， hsa-miR-188-5p， hsa-miR-663a， hsa-miR-135a-5p and hsa-miR-4707-5p in plasma exosomes of GDM pregnant women were up-regulated. The area under the ROC curve （AUC） of these four miRNAs for GDM prediction was 0.839 （95%CI：0.724~0.954）. The target genes of miR-135a-5p were involved in insulin signaling pathways. ConclusionsDifferentially expressed exosomal miRNAs in GDM plasma act as potential predictors of GDM. Among them， miR-135a-5p mainly participates in insulin signaling pathways.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective This study aimed to evaluate the effects of in-utero exposure to HIV and ART on pregnancy outcome and early growth of children.Methods This cohort study enrolled 802 HIV-infected pregnant women between October 2009 and May 2018 in Guangzhou,China The women were assigned to receive combination ART (cART) or mono/dual ART or no treatment.The primary outcomes were the combined endpoints of any adverse pregnancy outcome [including ectopic pregnancy,spontaneous abortion,stillbirth,preterm birth,small for gestational age (SGA)] and adverse early growth outcome (including infant death,HIV infection of mother-to-child transmission,and underweight,wasting and stunting of infants at 4 weeks of age).Results Adverse pregnancy outcomes occurred in 202 (35.1％) of all enrolled HIV-infected women,and 121 (31.3％) of all infants exhibited adverse effects on early growth at 4 weeks of age.The rates of adverse pregnancy outcomes,spontaneous abortion,ectopic pregnancy,stillbirth,infant death and perinatal HIV infection were higher among women not receiving ART,compared to those treated with cART or mono/dual ART (P ＜ 0.05).However,women treated with cART had a higher rate of SGA,compared to untreated women (P ＜ 0.05).No differences in early infant growth were observed among the different treatment regimens.Conclusion Our findings underscore the essentiality of prioritizing HIV-positive pregnant women for ART,as even mono/dual ART available in resource-limited countries could improve pregnancy outcomes and infant survival

Brain ; pathology ; Electroconvulsive Therapy ; adverse effects ; Humans ; Schizophrenia ; therapy

Astragalus membranaceus (Radix Astragali, RA) and Atractylodes macrocephala (Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control media or media containing spermidine (5 μmol·L, SPD), alpha-difluoromethylornithine (2.5 mmol·L, DFMO), 4-Aminopyridine (40 μmol·L, 4-AP), the polysaccharide extracts of RA or RAM (50, 100, or 200 mg·L), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca ([Ca]) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca] and accelerated migration of IEC-6 cells, compared with the controls (P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca], but also restored IEC-6 cell migration to control level (P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased (P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0 : 14.1 : 0.3 : 19.9 : 181.3 : 6.3 in RA and 1.0 : 4.3 : 0.1 : 5.7 : 2.8 : 2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.
Animals ; Astragalus propinquus ; chemistry ; Atractylodes ; chemistry ; Cell Line ; Cell Movement ; drug effects ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Intestines ; cytology ; drug effects ; Kv1.1 Potassium Channel ; genetics ; metabolism ; Polyamines ; metabolism ; Polysaccharides ; chemistry ; isolation & purification ; pharmacology ; Rats ; Rhizome ; chemistry ; Signal Transduction ; drug effects ; rhoA GTP-Binding Protein ; metabolism

Objective To investigate the role of the 5-hydroxymethylcytosine (5-hmC) DNA modification in the onset of systemic lupus erythemosus (SLE),we compared tihe levels 5-hmC between SLE patients and normal controls.Methods With informed consent,whole blood was obtained from patients,and genomic DNA was extracted.Using hMeDIP-seq analysis and validation by quantitative real-time quantitative polymerase chain reaction (RT-PCR),we identified the differentially hydroxymethylated regions that were associated with SLE.Results There were 1 701 genes with significantly different 5-hmC levels at the promoter region in the SLE patients compared with the normal controls.The CpG islands of 3 826 genes showed significant difference at 5-hmC levels in SLE patients compared with the normal controls.Out of the differentially hydroxymethylated genes,three were selected for validation,including TREX1,CDKN1A,and CDKN1B.The hydroxymethylation levels of these three genes were confirmed by quantitative RT-PCR.Conclusion Our studies indicate that there are significant alterations of 5-hmC in SLE patients;these differentially hydroxymethylated genes may contribute to the pathogenesis of SLE.Such novel findings show the significance of 5-hmC as a potential biomarker or promising target for epigenetic-based SLE therapies.

Objective To investigate the effects of lentiviral-mediated RNA interference (RNAi) targeting tumor necrosis factor-α(TNF)-αgene on the expression of TNF-α, interleukin (IL)-1β, IL-6 of murine macrophages RAW264.7, and the efficiency of RNAi experimental gene therapy for the murine collagen-induced arthritis (CIA). Methods The RAW264.7 macrophages were infected by lentivirus-RNAi particles, then stimulated by Lipopolysaccharides (LPS). The TNF-α, IL-1β, IL-6 expression of RAW264.7 macrophages were measured with real-time polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA). CIA models were esta-blished in DBA/1 mice using bovine type Ⅱ collagen. The treatment effect of lentivirus-RNAi on CIA were observed through arthritis scores, serum TNF-α measurement and hind paw paraffin section hematoxylin/eosin staining after lentivirus-RNAi particles tail vein injection. Results The TNF-αmRNA relative expression level of lentiviral RNAi group was 0.291 ±0.021, significantly lower than that of negative control group 0.925±0.013 (t=25.4, P<0.01). The inhibition rate in mRNA levels was 68.5%. The serum TNF-α level of lentiviral RNAi group was [(249 ±11) ng/ml], significantly lower than that of negative control [(382±6) ng/ml] (t=10.31, P<0.05). The inhibition rate of protein levels was 34.7%. It had no effect on the IL-1β and IL-6 mRNA expression. On the 8th day after systemic administration, the arthritis score of lentivirus-RNAi group was 2.50±0.19, which was significantly lower than that of blank controls (3.63 ±0.18) and negative controls (3.75 ±0.16) (F=42.8, P<0.01). From now on, arthritis score of lentivirus-RNAi group and positive control decreased slowly to at least 2 weeks after treatment induction. The serum TNF-α levels of lentivirus-RNAi group and positive controls were [(35±6) pg/ml] and [(32±7) pg/ml] significantly lower than that of negative controls [(47±3) pg/ml] (t=3.03, 4.11, P<0.01) respectively. Morphological examination showed that the lentivirus-RNAi decreased CIA pathological manifestations. Conclusion Lentiviral-mediated RNAi targeting murine TNF-α gene can effectively inhibit TNF-α expression both in vitro and in vivo, which also effectively improve the CIA arthritis score. Lentiviral-mediated RNAi targeting TNF-αgene provides a potential strategy for rheumatoid arthritis (RA) treatment.

OBJECTIVESTo investigate the safety and efficacy of yangxinkang tablets in patients with chronic heart failure (CHF) and syndrome of qi and yin deficiency, blood stasis, and water retention.

METHODSIn a double-blinded, randomized, placebo-controlled, multicenter clinical trail, 228 patients with CHF New York Heart Association (NYHA) class II or III in stage C were assigned by randomized block method to two groups in a 1:1 ratio to undergo either conventional Western treatment or conventional treatment plus yangxinkang tablets for 4 weeks. The outcome measure were effect of cardiac function, Chinese medicine (CM) syndromes, scores of symptoms, signs, and quality of life measured by Minnesota Living with heart failure questionnaire (MLHFQ) before and after the treatment.

RESULTSTotally 112 patients were analyzed in the treatment group and 109 in the control group. They were comparable in NYHA functional class, basic parameters and primary diseases before treatment. Cardiac function and CM syndromes were greatly ameliorated in both groups after treatment. Total effective rates of cardiac function and CM syndrome in the treatment group were significantly higher than those in the control group (P<0.05). Total symptom score and sign score in the treatment group decreased significantly after treatment (P<0.01), which were significantly lower than those in the control group (P<0.05). There were statistically significant differences in post-treatment scores of gasp, cough with phlegm, pulmonary rales and jugular vein engorgement between the two groups (P<0.05 or P<0.01). Three MLHFQ scores decreased significantly in both groups after treatment (P<0.01). Post-treatment total scale score and physical subscale score in the treatment group and the reduction of them showed statistically significant differences (P<0.05) as compared with the control group. There was no significant difference between the two groups in emotional subscale score and the reduction after treatment (P>0.05). There was no obvious adverse reaction in either group noted during the study.

CONCLUSIONSYangxinkang tablets were safe and efficacious in improving cardiac function, CM syndromes, symptoms, signs, and quality of life in patients with CHF class II or III in stage C on the base of conventional treatment.

Aged ; Chronic Disease ; Double-Blind Method ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Heart Failure ; drug therapy ; physiopathology ; Humans ; Male ; Quality of Life ; Surveys and Questionnaires ; Tablets