The role of TLR4/MyD88/NF-κB in the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis.

OBJECTIVE: To investigate the effect of the TLR4/MyD88/NF-κB (Toll-like receptor 4/myeloid differentiation factor/nuclear factor kappa B) signalling pathway on the protective effect of ulinastatin on the intestinal mucosal barrier in mice with sepsis. METHODS: A mouse model of sepsis was established by classical caecal ligation and perforation. Forty-four SPF C57BL/6 mice were randomly divided into the following four groups with 11 mice in each group: the control group (Con group), ulinastatin group (Uti group), Uti + LPS (lipopolysaccharide, LPS) group (Uti + LPS group) and LPS group. Mice in the Con group and Uti group received saline or ulinastatin injected 2 h after modelling; Mice in the Uti + LPS group received LPS injected 0 h after modelling, other procedures were the same as in the Uti group; Mice in the LPS group received LPS only. At 48 h after surgery, the levels of TNF-α (tumour necrosis factor-α, TNF-α), IL-6 (interleukin-6, IL-6) and IL-1ß (interleukin-1ß, IL-1ß) in vein, and the expression of TLR4, MyD88 and NF-κB mRNA in small intestinal mucosa tissues using ELISA and RT‒PCR. RESULTS: The pathological specimens showed increased inflammatory injury in the Con and LPS groups, while these injuries and changes improved in the Uti group. The scores of intestinal mucosal injury at 48 h of Uti injection were significantly lower than those of the Con group (P < 0.001), while the scores of intestinal mucosal injury of Uti + LPS were significantly higher than those of the Uti group (P = 0.044). The expression of TNF-α, IL-6 and IL-1ß in the Uti decreased significantly at 48 h after surgery than that in the Con group (P = 0.001, P = 0.014, P = 0.004), while the expression of TNF-α, IL-6 and IL-1ß in the Uti + LPS group increased significantly after surgery than that in the Uti group (P = 0.026, P = 0.040, P = 0.039). The expression of TLR4, MyD88 and NF-κB mRNA in the Uti group decreased significantly compared with that in the Con group (P = 0.001, P = 0.021, P = 0.007), while the expression of TLR4, MyD88 and NF-κB mRNA in the Uti + LPS group was higher than that in the Uti group (P = 0.023, P = 0.040, P = 0.045). CONCLUSION: These findings indicate that the protective effect of ulinastatin on the intestinal mucosal barrier against sepsis may be mediated through the TLR4/MyD88/NF-κB pathway.

MicroRNA-20b-5p regulates propofol-preconditioning-induced inhibition of autophagy in hypoxia-and-reoxygenation-stimulated endothelial cells.

Ischemia-reperfusion (IR) injury is a major cause of clinical emergencies during and after surgical procedures. Propofol protects the heart from cardiovascular IR injury by inhibiting autophagy. MicroRNAs (miRNAs) participate in anesthetic-regulated cardiovascular injury. MiR-20b-5p targets unc-51-like autophagy activating kinase 1 (ULK1). Its role in propofol-modulated cardiovascular IR injury remains unclear, however. In this study, we used an in vitro model of hypoxia-reoxygenation (HR)-induced injury to human umbilical vein endothelial cells (HUVECs) to determine the protective effect of miR-20b-5p in cells preconditioned with propofol. We found that miR-20b-5p was significantly higher and ULK1 was lower in propofol-preconditioned HUVECs with HR injury than in HUVECs with HR injury only. Additionally, miR-20b-5p overexpression increased cell viability and repressed autophagy and apoptosis more in propofol-preconditioned HUVECs with HR injury than in HUVECs with HR injury only. A luciferase reporter assay confirmed the target reaction between miR-20b-5p and ULK1. Overexpression of ULK1 restrained the protective effect of miR-20b-5p in propofol-preconditioned HUVECs with HR injury. In conclusion, our results indicate that propofol inhibits autophagic cell death via the miR-20b-5p-ULKI axis and that ULK1 may be a therapeutic target for cardiovascular IR injury.

Effects of different modes of mild treadmill exercise on cognitive function of Alzheimer's disease mice / 重庆医学

Objective To investigate the effects and possible mechanisms of different modes of mild treadmill exercise on cognitive function in Alzheimer's disease(AD) APP transgenic mice.Methods Twenty-four 6-month-old APP+ mice were randomly and equally divided into the four groups:control group(Con),regular exercise group(RE),irregular time-of-day exercise group (ITE) and irregular different duration exercise group(IDDE).After treadmill exercise,the spatial cognitive ability was tested.Soluble and insoluble Aβ40,42 levels,activity of β-secretase and γ-secretase in hippocampal tissue were compared among 4 groups.The mRNA levels of NEP,IDE and MMP-9 in the hippocampal tissue were detected.The number of hippocampal survival neurons and protein levels of BDNF,TrkB and p-TrkB were detected.Results Compared with the control group,the spatial cognitive ability in the RE group was significantly increased(P＜0.05),the levels of soluble and insoluble Aβ40,42 and activity of β-secretase and γ-secreatase were significantly reduced in the hippocampal tissue of th RE group(P＜ 0.05).However,the mRNA levels of NEP,IDE and MMP-9 had no statistically significant difference among the four groups(P＞0.05).Compared with the control group,the number of survival neurons and protein levels of BDNF and p-TrkB in the hippocampal of the RE group tissue were significantly increased(P＜0.05).The cognitive function,levels of Aβ40,42,BDNF and p-TrkB,number of survival neurons in the RE group had statistically significant differences when compared with the ITE and IDDE groups(P＜0.05).Conclusion Mild and regular treadmill exercise can effectively increase the cognitive function of AD mice,which might be related with the regulation of BDNF/TrkB pathway.

Overexpression of constitutively active MAP3K7 in ameloblasts causes enamel defects of mouse teeth.

OBJECTIVE: Compelling evidence suggests that mitogen-activated protein kinases (Mapks) play an important role in amelogenesis. However, the role of transforming growth factor (TGF)-ß-activating kinase 1 (Tak1, Map3k7), which is a known upstream kinase of Mapks, during amelogenesis remains to be determined. The aim of this study was to investigate the possible involvement of Map3k7 in amelogenesis. DESIGN: We generated transgenic mice that produced constitutively active human MAP3K7 (caMAP3K7) under the control of amelogenin (Amelx) gene promoter. Radiography and micro-computed tomography (µCT) analysis was used to detect the radio-opacity and density of the teeth. The enamel microstructure was observed with a scanning electron microscope. Histological analysis was used to observe the adhesion between ameloblasts and residual organic matrix of the enamel. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of enamel matrix protein. RESULTS: The enamel of mandibular molars in caMAP3K7-overexpressing mice displayed pigmentation and a highly irregular structure compared with the wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. The gross histological appearances of ameloblasts and supporting cellular structures, as well as the expression of the enamel protein amelotin (Amtn) were altered by the overexpression of caMAP3K7. CONCLUSIONS: Our data demonstrated that protein expression, processing and secretion occurred abnormally in transgenic mice overexpressing caMAP3K7. The overexpression of caMAP3K7 had a profound effect on enamel structure by disrupting the orderly growth of enamel prisms.

Study on the levels of microRNA-146b, microRNA-155 and microRNA-30b in human milk and their correlation with maternal and infant health / 中华实用儿科临床杂志

Objective To explore the expression levels of immune-related microRNA-146b (miR-146b),microRNA-155 (miR-155) and microRNA-30b(miR-30b) in human breast milk and its relationship with maternal and infant's health.Methods One hundred and thirty-four mothers and their infants from obstetrical department were recruited in the study after delivery.The subjects were divided into 2 groups,breast feeding group(n =86) and formula-feeding group(n =48),and were followed up 3 months after delivery.Breast milk samples were collected at 2-5 days after delivery(colostrum) and 3 months after delivery(mature milk).The expression levels of microRNAs in milk samples were detected by real-time PCR.The relationship between levels of microRNAs and maternal and infant-related factors was analyzed.Results 1.MiR-146b,miR-155 and miR-30b expressions were abundant both in human colostrums (5.950 ± 0.823,3.899 ± 0.920,4.057 ± 0.604) and mature milk (4.840 ± 0.805,2.128 ± 0.969,4.929 ± 0.566).The levels of miR-146b and miR-155 were higher in colostrum than that of mature milk (t =7.716,10.215,all P ＜ 0.01),while the level of miR-30b was higher in mature milk than that of colostrums(t =-8.626,P ＜ 0.0l).2.Additionally,the level of miR-30b was negatively correlated with maternal pre-pregnancy body mass index (r =-0.298,P ＜ 0.01).3.The levels of miR-146b and miR-30b were higher in mothers giving birth by vaginal delivery than those who underwent cesarean section(t =2.356,3.108,all P ＜0.05).4.The levels of miR-146b and miR-155 were higher in colostrum-fed girls than boys (t =-2.204,-2.985,all P ＜ 0.05).5.The level of miR-146b in mature milk was negatively correlated with 3-month-old infant' s Z score of body weight (r =-0.425,P ＜ 0.05) and body length (r =-0.569,P ＜ 0.01).6.During follow-up,the incidence of baby eczema in breast feeding group (8.82％,3/34 cases) was lower than that in formula milk feeding group(29.17％,14/48 cases) (x2 =5.012,P =0.025).Conclusions The levels of immunocompetent microRNAs in human milk are influenced by the lactation period,maternal prepregnancy body mass index,mode of delivery and infant sex.The immune-related microRNAs in human milk could be involved in the regulation of infant's immunity and growth.

Twin pregnancy outcomes of maternal hepatitis B virus carrier state / 中华围产医学杂志

To investigate the impact of maternal hepatitis B virus (HBV) carrier state on twin pregnancy outcomes. Methods From January 2004 to December 2012, 569 women with twin pregnancy were hospitalized in Nanjing Drum Tower Hospital. Thirty-two women positive for hepatitis B surface antigen (HBsAg)(negative for hepatitis B e antigen, with normal liver function before conception)were included in the HBsAg-positive group and the other 537 women were included in the HBsAg-negative group. The pregnancy outcomes of the two groups were compared by t test and Chi-square test. The risk factors for neonatal birth weight were analyzed by multivariate regression analysis. Results Compared with the HBsAg-negative group, the HBsAg-positive women had a higher incidence of abnormal liver function (alanine aminotransferase≥50 U/L) [18.8% (6/32) vs 5.8% (31/537), χ2=6.367, P=0.012]. The incidence of gestational diabetes mellitus was 21.9% (7/32) in the HBsAg-positive group, which was higher than in the HBsAg-negative group [11.6% (62/537)], although the difference was not significant (χ2=2.132, P=0.144). The incidences of intrahepatic cholestasis of pregnancy,hypertensive disorders complicating pregnancy, premature rupture of membranes, placenta previa, fetal distress, postpartum hemorrhage, preterm birth, caesarean section, umbilical cord around the neck, meconium-staining amniotic fluid and neonatal asphyxia were no statistical difference between two groups (all P<0.05, respectively). Multivariate regression analysis showed that gestational diabetes mellitus (β=67.869, 95%CI: 0.494-135.244, P=0.048), maternal age (β=6.592, 95%CI: 2.020-11.880, P=0.006) and gestational age (β=164.069, 95%CI:154.426-173.712, P<0.01) were risk factors for neonatal birth weight, but not the maternal HBsAg-positive status (β=78.864, 95%CI: -16.950-174.678, P=0.107). Conclusion Twin pregnancy and HBV carrier state increase the risk of abnormal liver function, but not other adverse pregnancy outcomes and newborn diseases.

Clinical Observation on Oral Use of Herbal Medicine Combined with Ultrasonic Wave and Herbal Medicine Mask for Acne Simplex / 广州中医药大学学报

[Objective] To observe the therapeutic effect of oral use of heat-clearing, damp-removing and toxicity-clearing herbal medicine combined with ultrasonic wave and herbal medicine mask treatment in treating acne simplex (AS). [Methods] Two hundred and ten cases of AS were randomized into groups A and B. Group A ( n=113) was treated with modified Yinchenhao Decoction and Qingfei Decoction for oral use and added with ultrasonic wave and mask prepared with herbal medicine including Borneolum Syntheticum, Flos Lonicerae, Radix Scutellariae, Radix Salviae Miltiorrhizae, Fructus Forsythiae; group B ( n=97) was treated with metronidazole 0.2 g, tid, and vitamin Bg 20mg, tid, as well as erythromycin ointment for external application. After a 4-week treatment, the therapeutic effect was compared. [Results] The total effective rale was 80.6% in group A and 41.3% in group B, and the markedly effective rate was 50.5% in group A and 28.9% in group B, the difference being significant (P

Combined Treatment of Chinese Herbs with Autoepidermic Grafting for Vitiligo / 广州中医药大学学报

[Objective] To observe the therapeutic effect of wind - dispelling, blood - activating and stasis - removing Chinese herbs combined with autoepidermic grafting for vitiligo. [Methods] Forty cases of vitiligo were randomized into two groups: 28 cases in Group A were treated with Chinese herbs combined with autoepidermic grafting (235 grafts in all) and 12 in Group B with autoepidermic grafting (118 grafts in all) alone. [Results] In Group A, 1 case was cured, 13 were markedly effective, 10 effective and 4 ineffective and 0, 3, 3, and 6 in Group B respectively. The therapeutic effect in Group A was superior to that in Group B (P = 0.034). [Conclusion] Chinese herbs combined with autoepidermic grafting has a better effect than autoepidermic grafting alone for vitiligo.

A Clinical Observation on Mixture Portulacae Co.in Decreasing the Recurrence Rate of Condyloma Acuminatum / 广州中医药大学学报

0.05 ),and the recurrence rate in Group Ⅲ was highest,the difference beingsiedcant as compared with Group Ⅰ(P