Multiple evanescent white dot syndrome (MEWDS) is an acute retinal disease characterized by multifocal white spots in the fundus often seen in the unilateral eye. The lesions mainly involve the retinal pigment epithelium and the outer retinal structure. Typical ocular manifestations of MEWDS include grayish-white outer retinal spots with a clear borderline identified on the fundus, findings of hyper-autofluorescence in the early stage consistent with the spots identified on the fundus, and the optical coherence tomography manifestation of multifocal disruption of the ellipsoid zone. With the rapid development of multimodal imaging technology, some scholars found that these manifestations are not exclusive to MEWDS as some types of chorioretinopathy can also show MEWDS-like changes. The etiology of these diseases may be inflammation, infection, immunity, or tumor-related, misdiagnosed by masquerading as MEWDS. Here we summarized the clinical manifestations and imaging features of MEWDS and reviewed the fundus lesions changes that can be misdiagnosed as MEWDS.

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

OBJECTIVE To investigate whether electroacupuncture(EA)ameliorates abnormal trigeminal neuralgia(TN)orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.METHODS A mouse infraorbital nerve transection model(pT-ION)of neuropathic pain was established,and EA or sham EA was used to treat ipsilateral acu-puncture points(GV20-Baihui and ST7-Xia-guan).Golgi-Cox staining and transmission elec-tron microscopy(TEM)were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.RESULTS Stable and per-sistent orofacial allodynia and anxiety-like behav-iors induced by pT-ION were related to changes in hippocampal synaptic plasticity.Golgi stain-ings showed a decrease in the density of dendritic spines,especially mushroom-type dendritic spines,in hippocampal CA1 neurons of pT-ION mice.TEM results showed that the density of synapses,membrane thickness of the postsynap-tic density,and length of the synaptic active zone were decreased,whereas the width of the synap-tic cleft was increased in pTION mice.EA attenu-ated pT-ION-induced orofacial allodynia and anx-iety-like behaviors and effectively reversed the abnormal changes in dendritic spines and syn-apse of the hippocampal CA1 region.CONCLU-SION EA modulates synaptic plasticity of hippo-campal CA1 neurons,and reduces abnormal oro-facial pain and anxiety-like behavior,providing evidence for a TN treatment strategy.

Objective To investigate six yearsˊ outcome of children with asthma. Methods Children with asthma diagnosed in the epidemiological survey of childhood asthma in urban area of Beijing in 2010 were selected in this study. The field follow-up was conducted in 2016(6 years later)to obtain information about asthma attack,di-sease control,medication usage,and comorbidities of allergic diseases. The skin prick test,lung function and exhaled ni-tric oxide were performed during field follow - up stage. Results Sixty - four children,aged 7 - 19 years old [(13. 59 ± 3. 48)years old],completed the field follow-up survey. Among 35. 9%(23/64 cases)children,the asth-ma symptoms still persisted within 2 years(without remission),while 64. 1%(41/64 cases)children had no symp-toms within 2 years and above(remission). The course of children without remission(9. 0 years)was significantly lon-ger than that of children with remission(5. 5 years),and there was statistical significance(z＝ -3. 775,P<0. 001). Among the children without remission,the number of uncontrolled children in the last month accounted for 13. 0%(3/23 cases),partially controlled for 17. 4%(4/23 cases),and under controlled for 69. 6%(16/23 cases). The majority of unrelieved children were treated with intermittent control drug[43. 5%(10/23 cases)υs. 12. 2%(5/41 cases), χ2 ＝8. 036,P<0. 01]. A total of 47. 8%(11/23 cases)of children without remission were completely unaffected by physical activity,while 92. 7%(38/41 cases)of children with clinical remission were completely unaffected by physi-cal activity(χ2 ＝14. 117,P<0. 001). The proportion of children without remission with eczema and atopic dermatitis lasting longer than 6 years old was 56. 5%(13/23 cases),which was significantly higher than that of children with re-mission[29. 3%(12/41 cases),χ2 ＝4. 598,P<0. 05]. In 2010 and 2016,there were 46 children with allergen re-sults. Compared with 2010,the proportion of animal fur and pollen allergy increased in 2016[19. 6%(9/46 cases)υs. 52. 2%(24/46 cases),36. 9%(17/46 cases)υs. 67. 4%(31/46 cases)],and there were statistical significances (χ2 ＝10. 632,8. 538,all P<0. 01). In 2016,the number and degree of total allergens in the clinical unrelieved chil-dren were higher than that in the relieved children. Further analysis showed that the unrelieved children had higher cigarette allergy positivity(21. 7% υs. 2. 5%,χ2 ＝4. 239,P<0. 05). There was no significant difference in lung func-tion and exhaling nitric oxide between the clinical unrelieved children and the relieved children. Conclusions Six years later,the proportion of animal fur and pollen allergy increased in children with asthma. Compared with children with remission,the children without remission had more treatment with intermittent control drug,with higher proportion of eczema and atopic dermatitis over six years old,and higher percentage of cigarette allergy positivity.

Objective To understand the outcome of asthma in children from urban area of Beijing and the factors associated with the outcome.Methods A total of 497 children with asthma diagnosed in the epidemiological survey of childhood asthma in urban area of Beijing in 2010 were selected in this study.Telephone follow-up was conducted in 2016 to obtain information about asthma attack,emergency visit,hospitalization,medication and disease control,and data of comorbidities of allergic diseases from 1 year earlier.Enumeration data were compared using chi-square test,measurement data were compared by rank sum test.The multi-factor logistic regression analysis was employed for the relationship between the related factors and asthma,Kaplan-Meier survival analysis and COX regression was employed to understand the relationship between the related factors and the course of the disease.Results Questionnaires were conducted in 366 children,of whom 66.7％ (244/366) were male,and 33.3％ (122/366) were female.Compared with 2010,the rate of asthma attack and emergency room visits in children in last 12 months were significantly lower (19.1％(70/366) vs.57.1％(284/497),and 3.0％ (11/366) vs.19.7％ (98/497),x2=125.910 and 53.352,both P＜0.01).There was no significant change in the proportion of allergic rhinitis and atopic dermatitis in last 12 months compared with that 6 years ago (both P＞0.05).The number of children with clinical remission (2 years and above) was 75.4％ (276/366).The number of children without remission within 2 years was 24.6％ (90/366).The majority of children without remission were less than 12 years old boys (52.4％ (33/63) vs.30.9％ (56/181),x2=9.273,P＜0.01).The proportion of children without remission associated with allergic rhinitis (67.8％(61/90)),atopic dermatitis (30.0％(27/90)),first-degree relatives with asthma (68.9％ (62/90)) was higher than that of children with remission (51.8％(143/276),17.0％(47/276),and 54.7％ (151/276),respectively,x2=7.013,7.079,5.608,respectively,all P＜0.05).The proportion of children without remission who used control drugs was (33.3％ (30/90)),which was higher than that in children with remission (7.2％ (20/276),x2=39.158,P＜0.01).Multiple logistic regression showed that boy (OR=2.402 (1.611-3.580),P＜0.05),later onset (OR=4.339 (＞3-6 years old vs.0-3 years old),OR=2.630(＞6 years old vs.0-3 years old),x2=18.512,31.371,6.510,all P＜0.05) were independent risk factors for asthma remission.COX regression analysis showed that the use of control drugs (HR=0.705 (0.515-0.964),x2=4.795,P＜0.05) was the relevant factor in the course of the disease.Conclusions With the increase of age,the incidence of asthma in children in Beijing city in recent 12 months reduced.Male and late onsets were independent risk factors for asthma remission.The use of control drugs was the relevant factor in the course of the disease.

Objective To evaluate the effectiveness of professional nurses in atrial fibrillation (AF) anticoagulation management system.Methods 217 consecutive patients with nonvalvular AF were enrolled.All patients received warfarin therapy for 3-6 months after catheter ablation for AF,who were divided into experimental group (n=102) and control group (n=115) by random digits table.The patients of control group adjusted their warfarin doses by following doctor's advice when discharged and by visiting the outpatient clinic regularly after discharged.The patients of treatment group adjusted their warfarin doses under the guidance of one well-trained nurse.Days of the international normalized ratio (INR) value achieved therapeutic anticoagulation range (2.0-3.0) for the first time,the effective anticoagulation rate that defined as more than 70％ of INR values between 2.0-3.0 after titration period,the ratio of times of INR value 2.0-3.0 to total times after titrating and INR monitoring frequency were compared between the 2 groups.Results In treatment group,days of the INR value achieved therapeutic 2.0-3.0 for the first time were less than that in control group (8 d vs.15 d,P＜0.01),the effective anticoagulation rate [45.1％(46/102)] and the ratio of times of INR value 2.0-3.0 to total times after titrating (67.6％±18.5％) was significantly higher than that in control group [31.3％(36/115) and 62.0％±23.1％ respectively,P＜0.05].INR monitoring during the whole period and after titrating were more frequently in treatment group [(9.4±2.2)times vs.(8.4±2.7) times,P＜0.05;(7.9±2.4) times vs.(6.3±2.8) times,P＜0.01].The number of patients in treatment group who monitor INR less than 3 times after titrating was larger than that in control group (18 vs.1,P＜0.01).Conclusions The participation of professional nurses in atrial fibrillation anticoagulation management system was helpful not only in achieving INR 2.0-3.0 more quickly but also in improving the effective anticoagulation rate.

The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan.

BackgroundThe relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechan-isms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels.MethodsWe collected data of clinical characteristics, echocardio-graph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels[including total cho-lesterol(TCL), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), and triglycerides(TG)]and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area.ResultsThere was a significantly inverse correlation between TCL le-vels and RVEDD (r=-0.34,P<0.001) and RA (r=-0.36,P<0.001). Other lipids such as LDL-C, HDL-C, and TG had asimilar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use.ConclusionsLipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as wellas identify a causal relationship, if any.

Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure. Methods We retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis. Results In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001). Conclusions There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.