Objective:To explore the placental expression of farnesoid X receptor( FXR) ,as well as the total bile acid (TBA) levels in maternal and umbilical cord serum in intrahepatic cholestasis of pregnancy (ICP) and normal late pregnancy. To evaluate the roles of placental FXR in the pathological mechanism of ICP. Methods:Maternal and umbilical cord blood as well as placentas were collected in gravidas of 33 ICP (ICP group) and 33 normal late pregnancy (control group). According to maternal serum TBA levels, ICP group was divided into mild and severe subgroup, the latter with TBA ≥40 μmol/L TBA levels were measured by velocimetry and the placental FXR mRNA expression were examined by real time nested RT-PCR. Results:①Comparing the rate of meconium -stain of amniotic fluid: The rate in ICP group was significantly higher than that in control group(χ~2=7.543,P=0.013); The rate in serve ICP group was significantly higher than that in mild ICP group(χ~2= 7.637,P=0.013). ②The expression of FXR mRNA in placentas: placental FXR mRNA expression was significantly higher in ICP group than that in control group (z = -2. 391, P = 0.017). Placental FXR mRNA expression was higher in severe ICP group than that in mild ICP group (z= -2.391 ,P=0.017).③ln ICP group, a positive correlation was found between the placental FXR mRNA expression and the maternal serum TBA levels as well as umbilical serum TBA levels(r_s =0.348,P=0.047; r_s =0.284,P=0.027). There were no significant correlations between maternal serum as well as umbilical serum TBA levels and placental FXR mRNA expression in control group ( r_s = - 0.068, P = 0.716; r_s = 0.010,P=0.959). Conclusions:Placental FXR mRNA expression is up regulated by increased bile acid levels in ICP, which may represent a compensatory (anti-cholestatic) mechanism of placenta in ICP.

Objective To study the mechanism of adaptive immunity against Rhizopus arrihizus (R. arrihizus) infections. Methods Bone marrow derived dendritic cells (BMDCs) were separated from C57BL/6 mice and Card9-/- mice and then were cultured in vitro. Resting spores and swollen spores of R. arrihizus were in vitro co-cultured with BMDCs with or without Syk inhibition. Secretion of cytokines ( IL-23, IL-1βand IL-12) was analyzed by ELISA after 24 hours of culture. Na?ve T cells derived from C57BL/6 mice were in vitro co-cultured with spore-stimulated BMDCs for four days. Levels of IL-17A and IFN-γ in supernatants of cell culture were analyzed by ELISA. Flow cytometry was performed to analyze T cell differ-entiation. Confocal microscopy was used to observe the images of stained β-glucan on the surface of resting and swollen spores. Swollen spores were co-cultured with Dectin-1, Dectin-2, TLR2 and mannose receptor ( MMR) , and the binding results were analyzed by flow cytometry. Results Swollen spores but resting spores could induce the maturation of BMDCs and promote the secretion of cytokines (IL-23, IL-1βand IL-12). Co-culturing T cells with swollen spore-stimulated BMDCs enhanced their differentiation to Th17 and Th1. In addition, swollen spores promoted the secretion of Th1-related cytokine ( IFN-γ) and Th17-related cytokine (IL-17A). Adding Syk inhibitor to Card9-/-BMDCs or wild type BMDCs significantly inhibited the secretion of cytokines and T cell differentiation, especially in the Card9-/- group. β-glucan was overserved on the surface of swollen spores, but not on resting spores. On the surface of swollen spores existed pathogen associated molecular patterns ( PAMPs) that could bind with Dectin-1 and TLR2. Conclusion Swollen spores of R. arrihizus could active BMDCs to secrete cytokines of IL-23, IL-1β and IL-12 and trigger T cell responses in vitro. The possible mechanism might be associated with β-glucan exposed on the surface of swollen spores that binds with Dectin-1. The responses between BMDCs and R. arrihizus are Syk-Card9-dependent.

Objective To compare the effects of remifentanil infused at different rates on median effective target plasma concentration (EC50) of propofol inhibiting responses to laryngeal mask airway (LMA) insertion and determine the optimum infusion rate of remifentanil when used for fiberoptic bronchoscopy in pediatric patients.Methods Eighty-four ASA Ⅰ or Ⅱ pediatric patients,aged 7 months-3 years,scheduled for elective fiberoptic bronchoscopy,were randomly assigned into 3 groups (n =28 each):normal saline group (group C),remifentanil infused at 3 ng· kg-1 ·min-1 group (group R1) and remifentanil infused at 5 ng· kg-1 · min-1 group (group R2).Responses to LMA insertion were defined as body movement and/or bucking during insertion.The initial target plasma concentrations of propofol were 5.2,4.8 and 4.4 μg/ml in groups C,R1 and R2,respectively.The target plasma concentration of propofol was determined by up-and-down sequential allocation.Each time the target plasma concentration increased/decreased by 0.2μg/ml.EC50 and 95 ％ confidence interval of propofol blunting responses to LMA insertion were determined by probit method.Results EC50 (95 ％ confidence interval) of propofol was 5.03 (4.92-5.12) μg/ml,4.71 (4.58-4.84) μg/rnl and 4.46 (4.20-4.94) μg/ml in groups C,R1 and R2,respectively.There was no significant difference in EC50 of propofol between groups R1 and C (P ＞ 0.05).EC50 of propofol was significantly lower in group R2 than in groups C and R1 (P ＜ 0.05).Conclusion The infusion rate of remifentanil should not be lower than 5 ng· kg-1· min-1 when combined with propofol in pediatric patients undergoing fiberoptic bronchoscopy.

Objective To investigate the validity and reliability of Item Erectile Function Scale (I-EF) for neurogenic erectile dysfunc-tion (ED). Methods 104 patients with spinal cord injury were assessed with I-EF. They were measured with pudendal somatosensory ner-vous evoked potential (SEP), bulbocavernosus reflex potential time (BCR) and nocturnal penile tumescence (NPT) detection. 34 patients ac-cepted medicine for ED, and were assessed with I-EF after treatment. 21 patients with medium ED were assessed by 2 testers, and retested 2-4 weeks later. Results The patients who recorded their potential of SEP and BCR got the scores of Q1, Q2 above 7, and the absence with the scores of 3. Those found NPT 1-3 times got the score of Q3 above 7, and the absence with the scores of 3. The incidence of reflex erec-tions and NPT were more in complete suprasacral ones than in complete sacral ones (P<0.05). There was significant improvement after med-ication in patients with mild to medium ED (P<0.05). The interclass correlation coefficient (ICC) was 0.93 between testers and 0.90 between test-retest. Conclusion I-EF can be used to assess neurogenic erectile dysfunction for rehabilitation.

Objective To investigate the prevalence of dyslipidemia and the relationship between breakfast frequency and dyslipidemia in residents over 40 years old in Yiling area of Yichang City in Hubei Province. Methods A random sampling was conducted, and 10 420 inhabitants were investigated during 2011 to 2012. Results The morbidity of dyslipidemia was 64. 0%. It was significantly higher in female than in male (65. 9% vs 60. 6%). Compared with regular breakfast eaters, non-breakfast eaters had significantly higher morbidity of higher blood low density lipoprotein-cholesterol(LDL-C) and hypertriglyceridemia(P<0. 05). The risk of elevated serum LDL-C was higher in the non-breakfast eaters group(OR=2. 382, 95%CI 1. 300-4. 367, P=0. 019) after adjusted by age, sex, smoking, drinking, etc. Conclusions Compared with regular breakfast eaters, breakfast skippers had significantly higher morbidity of dyslipidemia. Eating breakfast on daily basis may have a significant protective effect on preventing dyslipidemia.

Objective To research the incidence and etiological factors of intraocular pressure(IOP)elevation in patients in early and late postop?erative stages after vitrectomy. Methods The clinical data of 235 cases(306 eyes)who underwent vitrectomy in our hospital were respectively ana?lyzed. IOP was measured before operation,in the early postoperative stage(within 2 weeks)and in the late postoperative stage(6 months after opera?tion or longer)by non?contact tonometer. Risk factors related with ocular hypertension happened in the early and late postoperative stages were statis?tically analyzed. Results The mean average IOP before operation was 15.3 ± 4.1 mmHg for the 306 eyes. Within the follow?up period of 6?20 months(mean,14.3 months),ocular hypertension occurred in 42 eyes[incidence,13.7%;mean,31.9 ± 6.0 mmHg]in the early postoperative stage and in 12 eyes[incidence,3.9%;mean,32.1 ± 5.7 mmHg]in the late postoperative stage. Logistic regression analysis revealed that lensecto?my,scleral buckling,cyclophotocoagulation,inert gas filling,silicone oil tamponade and diabetic retinopathy were the independent risk factors of oc?ular hypertension in early postoperative stage after vitrectomy,while lensectomy,scleral buckling,pan retinal photocoagulation,silicone oil tampon?ade,diabetic retinopathy and carotid artery stenosis were the independent risk factors of ocular hypertension in late postoperative stage after vitrecto?my. In addition,cyclophotocoagulation was a protective factor of IOP in the late postoperative stage. Conclusion The risk factors of ocular hyperten?sion after vitrectomy include the intraocular gapfiller,the mode of combined operation,disease type and carotid artery stenosis. IOP elevation that happens in the late postoperative stage is more harmful. Ocular hypertension in the late postoperative stage is not associated with that in the early stage.

ObjectiveTo explore the effects of the conjugate prepared from the cholera toxin B subunit(CB) and nerve growth factor(NGF) on the spatial learning and memory abilities and cholinergic function.MethodsThe conjugate of CB-NGF was prepared by the improved sodium metaperiodate method and nasally administrated to the β-amyloid protein(Aβ25-35) induced amnesic mice for 7 days with 2 dosage (7-5 μg/d、15 μg/d). Spatial learning and memory abilities were evaluated by Morris water maze and cholinergic function was assessed with the choline acetyl transferase (ChAT) immunohistochemical methods.ResultsMorris water maze test showed that the escape latency in Aβ25-35-treated mice prolonged and the staying time reduced in the crossed first quadrant where the platform had been located, compared with the control mice (P<0-01). In addition, the number of ChAT positive neuron declined in the model mice(P<0-001). CB-NGF nasal administration significantly shortened the escape latency and elevated the staying time and number of ChAT positive neuron(P<0-01).ConclusionCB-NGF treatment can improve the spatial and memory performance which may involve the neuroprotection to cholinergic system.

AIM: To investigate the immune stimulation capacity of B7-H1 blockade on immature dendritic cells (DCs) in vitro. METHODS: The human monocyte-derived dendritic cells were induced in the presence of cytokine GM-CSF and IL-4. The expression of B7-H1 was detected by FCM. On blockade of B7-H1, the maturation and endocytic activity, T cells stimulatory proliferation capacity, IL-12 production, T cell differentiation effect of DCs were detected by FCM, MTT assay, ELISA and ELISPOT, respectively. RESULTS: The expression of B7-H1 was increased with the induction of DCs. On day 7, the positive expression was 54.12%, and the TNF-? induced mature DCs had the positive expression rate of 83.64%. The blockade of B7-H1 on immature DCs had sharply increased their T cells stimulatory proliferation capacity and IL-12 production, and efficiently induced the development of Th1/Tc1 cells, but had no effect on their maturation and endocytic activity. CONCLUSION: The blockade of B7-H1 on immature DCs increases its immune stimulation activity. It is valuable to investigate the antitumor immune responses of DCs vaccine with B7-H1 blockade.

Objective To investigate the distribution of androgen receptor (AR) gene CAGrepeats in the Chinese Han nationality and its application in genetic diagnosis for Kennedy's disease (KD). MethodsRT-PCR,denaturing polyacrylamide gel electrophoresis (DPAGE) and gene sequencing were conducted for AR gene CAG repetition among 100 healthy controls and 28 patients diagnosed as motorneuron diseases,and the number of the repetition was counted. Results The healthy controls had a range of 15-31 times of CAG repetition,with an average of (23 ± 3) times.Among patients with motoneuron disease,3 cases with CAG repetition for more than 40 times (namely,46,47 and 47 times) were diagnosed as KD.The main clinical manifestations included slow progress of limb weakness,primarily in the proximal lower limbs,fatigue accompanied by myalgia,muscle jumping,muscle atrophy,elevated serum creatine kinase (CK) levels,neurogenic damage revealed by electromyogram (EMG) and androgen insensitivity.Conclusions The incidence of KDmay be underestimated in the Chinese population.Performing genetic diagnosis in patients with motor neuron disease for AR gene can improve clinical diagnosis and avoid misdiagnosis.

BACKGROUND:Long non-coding RNAs(lncRNAs),as important regulators of the inflammatory response,are involved in the immune-inflammation-brain crosstalk mechanism after ischemic stroke and have the potential to become a therapeutic agent for neurological dysfunction after ischemic stroke. OBJECTIVE:To analyze and summarize the molecular mechanism of lncRNA acting on glial cells involved in the neuroimmuno-inflammatory cascade response after ischemic stroke and the associated signaling pathways,pointing out that lncRNAs have the potential to regulate inflammation after ischemic stroke. METHODS:PubMed was searched using the search terms of"ischemic stroke,long non-coding RNA,neuroinflammation,immune function,signal pathway,microglia,astrocytes,oligodendrocyte,mechanism,"and 63 relevant documents were finally included for review. RESULTS AND CONCLUSION:In the early stage of ischemic stroke,the death of nerve cells due to ischemia and hypoxia activates the innate immune response of the brain,promoting the secretion of inflammatory factors and inducing blood-brain barrier damage and a series of inflammatory cascades responses.As an important pathogenesis factor in ischemic stroke,the neuroimmuno-inflammatory cascade has been proved to seriously affect the prognosis of patients with ischemic stroke,and it needs to be suppressed promptly in the early stage.Neuroinflammation after ischemic stroke usually induces abnormal expression of a large number of lncRNAs that mediate a series of neuro-immune-inflammatory crosstalk mechanisms through regulating the polarization of microglia,astrocytes and oligodendrocytes to exert post-stroke neuroprotective effects.LncRNAs,as important regulatory factors of the inflammatory response,inhibit the neuroimmuno-inflammatory cascade response after ischemic stroke through regulating nuclear factor-κB,lncRNA-miRNA-mRNA axis,Rho-ROCK,MAPK,AKT,ERK and other signaling pathways to effectively improve neurological impairment after ischemic stroke.Most of experimental studies on the interaction between lncRNAs and ischemic stroke are based on a middle cerebral artery occlusion model or a cerebral ischemia-reperfusion injury model,but no clinical trials have been conducted.Therefore,it remains to be further explored about whether lncRNAs can be safely applied in clinical practice.At present,there are many therapeutic drugs for the treatment of ischemic stroke,but there are relatively few studies on the application of lncRNAs,exosomes and other transplantation technologies for the treatment of ischemic stroke using tissue engineering technology,which need to be further explored.lncRNA has become an important target for the treatment of ischemic stroke with its relative stability and high specificity.In future studies,more types of inflammatory lncRNAs that function under ischemic-hypoxia conditions should continue to be explored,in order to provide new research directions for the treatment of neuroinflammation after ischemic stroke.