Study on the mechanism of Flos Puerariae and Semen Hoveniae in treatment of alcoholic liver injury based on network pharmacology and molecular docking / 浙江大学学报·医学版

OBJECTIVE@#To explore the mechanism of Flos Puerariae and Semen Hoveniae in treatment of alcoholic liver injury (ALI) based on network pharmacology and molecular docking.@*METHODS@#The information of chemical constituents and targets of Flos Puerariae and Semen Hoveniae was collected from TCMSP and Swiss databases, and the threshold values of oral bioavailability (OB) ≥ 30%, drug likeness (DL) ≥0.18 were used to screen the potential active compounds. The GeneCard and DrugBank databases were used to obtain the targets corresponding to ALI. The common targets were queried using Venn Diagram, and the network of PPI and Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed through DAVID and Reactome database. Autodock Vina software was used for molecular docking of potential ingredients and key targets.@*RESULTS@#A total of 21 potential active compounds and 431 therapeutic targets were gathered in Flos Puerariae and Semen Hoveniae, which involved 273 biological functions, 90 KEGG pathways and 362 Reactome pathways. The GO functions involved protein binding, ATP binding, etc.; the KEGG pathways mainly included PI3K-Akt signaling pathway and TNF signaling pathway; the Reactome pathways contained signal transduction and immune system, etc. The results of molecular docking showed that 21 potential active ingredients had good affinity with the core targets Akt1, TP53 and IL-6.@*CONCLUSIONS@#The network pharmacology and molecular docking analysis demonstrate the synergetic effect of Flos Puerariae and Semen Hoveniae with multi-compounds, multi-targets and multi-pathways in the treatment of ALI; and also predict the possible medicinal substance, key targets and pathways, which provides clues for the new drug development and mechanism research.

Efficiency and safety of genipin collagen crosslinking on rabbit cornea stroma model in vivo / 中华实验眼科杂志

Objective To evaluate the efficiency and safety of genipin collagen crosslinking (G-CXL) on rabbit corneas in vivo.Methods Forty healthy New Zealand white rabbits were randomly divided into 0.20％ G-CXL,0.25％ G-CXL,standard UVA-CXL and normal control group.And the right eyes were treated in different grouping.No procedures were performed in the normal control group.The corneal curvature (Km) and central corneal thickness (CCT) of right eyes were evaluated before,7 days and 14 days after crosslinking treatment.Cornea strips were harvested from the right eyes and tensile strain measurements were performed 7 days and 14 days after crosslinking treatment.The structure of corneal stroma was observed under light microscope (LM) and transmission electron microscope (TEM).Results No statistically significant differences in Km were observed among different groups or different timepoints (Fgroup =0.301,P=0.825;Ftime =1.287,P=0.284).Significant difference in CCTs was noticed among different time pionts (Ftime =3.786,P =0.029).Compared with preoperative,the CCTs of all the groups were significantly increased 7 days after crosslinking (all at P＜0.05).No significant difference in CCT was found among the groups (Fgroup =0.557,P=0.646).Seven days after crosslinking treatment,the Young's modulus at 10％ strain was (1 1.96±5.74),(21.24±6.77),(18.76±3.34) and (11.56±4.37) MPa in 0.20％ G-CXL group,0.25％ G-CXL group,UVA-CXL group and normal control group,respectively;the stress at 10％ strain was (0.68 ±0.24),(1.20 ± 0.25),(1.0l ± 0.30) and (0.69 ± 0.26) MPa,respectively;the Young's modulus and stress in 0.25％ G-CXL group was significantly increased when compared with those in 0.20％ G-CXL and normal control group (both at P＜0.05).No significant difference in Young's modulus and stress was observed between 0.25％ G-CXL group and UVA-CXL group (all at P＞0.05).Forteen days after crosslinking treatment,Young's modulus at 10％strain was (16.65±3.19),(19.12±2.39),(22.83 ±4.38) and (12.70±2.72)MPa in 0.20％ G-CXL group,0.25％ G-CXL group,UVA-CXL group and normal control group,respectively;stress at 10％ strain was (0.83 ±0.12),(0.97±0.04),(1.23±0.30) and (0.65±0.20) MPa,respectively;the Young's modulus and stress in UVA-CXL group was significantly increased,when compared with 0.20％ G-CXL group and normal control group (all at P＜0.05).Statistical significance of stress was observed between 0.25％ G-CXL group and UVA-CXL group (P =0.046).There is no significant difference in Young's modulus between 0.25％ G-CXL and UVA-CXL group (P =0.090).LM showed the reduction of keratocytes existed in superficial stroma of 0.20％ and 0.25 ％ G-CXL groups,while the reduction of keratocyte was found in anterior and intermediate stroma of UVA-CXL group.In 0.20％ and 0.25％ G-CXL groups,the ultrastructure of keratocytes was normal except vacuole in some keratocytes.Keratocytes apoptosis was noticed in UVA-CXL group and keratocytes was normal in deep stroma under TEM.Conclusions 0.25％ has a similar biomechanics effect when compared to UVA-CXL.Moreover,histological observation proves a better safety of G-CXL in comparison of UVA-CXL.

Research of diagnostic value of corneal biomechanical parameters based on Corvis ST in keratoconus / 中华实验眼科杂志

Objective To compare the corneal biomechanical properties between keratoconic eyes and normal eyes by using corneal visualization Scheimpflug technology (Corvis ST),and to evaluate the diagnostic value of corneal biomechanical parameters based on Corvis ST in keratoconus.Methods A prospective cases-control study was performed.Twenty-four keratoconic eyes from 17 patients and 40 normal eyes (right eye) from 40 participants were enrolled from October to December in Peking University First Hospital.Anterior segment parameters and refractive diopters were obtained with Topography (TMS-4) and mydriatic refraction.Biomechanical parameters were assessed with Corvis ST.Independent sample t-test and Wilcoxon rank sum test were used to compare the parameters of the two groups.The receiver operating characteristic (ROC) curves were plotted to distinguish keratoconus from the normal cornea.Diagnostic efficacies of all parameters were analyzed and some parameters were used as independent variables to establish a Logistic regression model.Results Maximum deformation amplitude of highest concavity (HCDA),maximum corneal velocity during the second applanation (Vout) and distance between both non-deformed peaks (PD) in the keratoconus group were higher than those in the normal control group,and first applanation time (A1T),cord length of first applanation (ALL),cord length of second applanation (A2L),radius value of central concave curvature at highest concavity (HCR) were lower than those in the normal control group,with significant differences between the two groups (all at P＜0.05).Maximum corneal velocity during the first applanation (Vin),second applanation time (A2T) and time taken to reach highest concavity (HCT) were insignificantly different between the two groups (all at P＞0.05).Many parameters had diagnostic values in keratoconus assessed by ROC analysis.HCR was the most efficient parameter showed by ROC evaluation (area under the curve was 0.927,sensitivity was 95.8％,specificity was 82.5％).The Logistic model were established with two independent variables,HCR (OR=0.205) and central corneal thickness (CCT) (OR=0.970).The forecast model of keratoconus diagnosis was established as follows:Logistic (P) =23.47-1.59×HCR-0.30×CCT.Diagnostic sensitivity and specificity were enhanced by using this model,the sensitivity was 95.8％,and the specificity was 95.0％.Conclnsions It is useful to evaluate the corneal biomechanical properties with Corvis ST.HCR is an efficient auxiliary testing index of diagnosis or screening of keratoconus.

Expression of costimulatory molecule inducible costimulator and coinhibitory molecule programmed death-1 in patients with myasthenia gravis / 中华神经科杂志

Objective To explore the immunopathological mechanism for the imbalance between the positive signal mediated by inducible costimulator (ICOS) and the negative signal mediated by programmed death-1 (PD-1) in patients with myasthenia gravis (MG).Methods Eighty-two patients with MG,56 healthy controls (HC) and 20 non-MG (NMG) patients,collected in the First Affiliated Hospital of Suzhou University from February 2014 to December 2016,were chosen to participate in the study.The expression of ICOS and PD-1 on peripheral blood mononuclear cells was detected by immuno-fluorescence staining and flow cytometry.The levels of soluble programmed death-1 (sPD-1),soluble programmed death ligand 1 (sPD-L1),IL-4 and other cytokines were detected by enzyme-linked immunosorbent assay.Results (1) Flow cytometry analysis:The co-expression of PD-1,ICOS on CD4 + T cells from MG group (9.64％ (8.82％)) was higher than in HC (1.81％ (2.10％),Z =-7.389,P ＜0.05) and NMG group (2.86％ (1.49％),Z =-4.636,P ＜ 0.05).The expression of ICOS on CD4 + T cells,ICOS ligand (ICOSL) on CD14+ monocytes and CD19+ B cells were increased in MG group comparing with that of the control groups.The proportion of PD-1 + CD4 + T cells (MG group 16.82％ (10.66％),HC 9.34％ (9.18％),Z =-4.345,P＜0.05;NMG group 7.07％ (3.40％),Z=-4.594,P＜0.05) and PD-1 Ligand (PD-L1) + CD14+ monocytes was higher in MG patients.All of these were detected by flow cytometry.(2) ELISA analysis:Serum sPD-1 expression significantly increased in MG group compared with that in the control groups (MG group (1.87 ± 0.64) ng/ml,NMG group (1.49 ± 0.70) ng/ml,t =2.04,P ＜ 0.05;HC (1.05 ± 0.50)ng/ml,t =2.08,P ＜ 0.05),while for serum sPD-L1,there was no significant difference between MG and control groups.(3) Serum cytokines detection:The expression of IL-4 was increased in MG patients (MG group (61.88 ±5.15) pg/ml,HC (32.03 ±1.84) pg/ml,t=2.50,P＜0.05;NMG group (42.62± 3.31) pg/ml,t =2.34,P ＜0.05),and there was a negative correlation between the expression of sPD-1 and the concentration of IL-4.Conclusions The increased expression of PD-1 + ICOS + CD4 + T cells suggested the subset involved in the pathological progress of MG.sPD-1 might disturb the ligation of PD-1 on T cells and PD-L1 on antigen presenting cells,while the ligation of ICOS and ICOSL passed positive signal,leading to over activity of the subsets and the progression of disease.

Feasibility of constructing keratectasia animal model using collagenase type Ⅱ / 中华实验眼科杂志

Background Keratoconus is a chronic and progressive non-inflammatory ectatic disorder characterized by corneal thinning and irregular corneal topography,and its pathgenesis is a hot topic.A suitable animal model of keratoconus is still lacking,which limits the progress of relevant research.Corneal ectasia is a main anatomical basis of keratoconus,so we assume that keratoconus model could be constructed by simulating corneal ectasia.Objective This study was to investigate the influence of collagenase type Ⅱ on biomechanical responses detected by corneal visualization Scheimpflug technology (Corvis ST) and the feasibility of construction of rabbit model of corneal ectasia using coliagenase type Ⅱ.Methods This study protocol was approved by Ethic Committee of Peking University First Hospital and followed the Statement about experimental animal use and care from Association for Research in Vision and Ophthalmology (ARVO).Keratectasia models were established in 10 right eyes of 10 New Zealand white rabbits by soaking 8 mm-diameter central cornea using collagenase type Ⅱ solution prepared by PBS solution containing 15％ dextran (200 μl of 5 mg/ml) for 30 minutes after epithelial debridement,and only 200 μl PBS solution containing 15％ dextran was used in the same way in the left eyes as controls.The average corneal curvature (Km) and central corneal thickness (CCT) were measured with hand-held electronic corneal curvature meter and corneal ultra-sonic pachymetry respectively before modeling and 14 days after modeling.Corneal biomechanical parameters and intraocular pressure were measured in vivo by using Corvis ST at day 14 after modeling.The rabbits were sacrificed at day 14 after modeling,and corneal sections were prepared for hematoxylineosin staining and transmission electron microscopic examination.Results There were no significant differences in Km and C CT between model group and control group before modeling (Km:[48.28±2.29] D vs.[48.82± 1.63] D;CCT:[356.50± 19.13] μm vs.[356.20±21.66] μm;both at P＞0.05).The Km increased to (48.87±2.27) D and CCT decreased to (340.40±19.84)μm at day 14 after modeling,which were significantly different from (46.86±1.47) D and (367.80±23.38)μm (both at P＜0.01).The maximal deformation amplitude of model group and control group was (1.25±0.07) mm and (1.15 ±0.13) mm,respectively,showing a considerable difference between them (t=2.65,P＜0.05).No significant differences were found in applanation 1/2 time,applanation 1/2 length,applanation velocity,radius of curvature and peak distance between the two groups (all at P＞0.05).The morphology and ultrastructure examinations revealed that the arrangement of collagen fibers was loose and disorder and the interfiber space was enlarged in comparison with control group.Conclusions Collagenase type Ⅱ can lower corneal biomechanical properties.Soaking of cornea with collagenase type Ⅱ may be a potential way to establish a keratectasia animal model.

Correlation between measurement of tear meniscus by anterior segment module of OCT with dry eye signs and symptoms / 中华实验眼科杂志

Background Dry eye is the most common ocular surface disease.Anterior segment pattern of optical coherent tomography (OCT) is able to be used to assess the tear meniscus directly and accurately.Objective This study was to evaluate the correlation between measuring outcomes of tear meniscus by anterior segment module of OCT with signs and symptoms of dry eye.Methods A retrospective serial cases-observational study was designed.Thirty-six patients who completed Ocular Surface Disease Index (OSDI) and got a score more than 20 were enrolled in the First Hospital of Peking University from September to October,2010 under the informed consent.The upper and lower tear meniscus height (U/LTMH,μm),depth (U/LTMD,μm) and cross sectional area (U/LMA,mm2) were measured with the anterior segment module of OCT (RTVue.pitch).A series of clinical tests were performed,including tear film interferometry,break-up time (BUT),fluorescein corneal staining,lissamine green conjunctival staining and Schirmer Ⅰ test (S Ⅰ t).The correlations of measuring outcomes of tear meniscus by anterior segment module of OCT with dry eye-related examinations were analyzed with Spearman correlation coefficients.Results The values of UTMH,UTMD,UMA were (232±56) μm,(156±53) μm,(0.021 ±0.008) mm2,respectively,and the values of LTMH,LTMD,LMA were (222 ± 72) μm,(163 ± 65) μm,(0.020 ± 0.006) mm2,respectively.No significant differences were found in the measuring values between the upper and the lower tear meniscus (all at P＞0.05).The quantitative values of tear meniscus were not significantly correlated with the OSDI scores or tear film interferometry grade.Significant correlations were seen between UTMH,UTMD,UMA and BUT (r=0.46,P=0.01 ;r=0.40,P=0.02;r=0.43,P=0.01).LTMH,LTMD,LMA were positively correlated with BUT (r=0.61,P=0.00;r=0.64,P=0.00;r=0.64,P=0.00) and S Ⅰ t (r=0.54,P=0.02 ;r=0.46,P=0.01;r=0.55,P=0.01) as well as negatively correlated with fluorescein cornealstaining (r=-0.37,P=0.04;r=-0.37,P=0.04;r=-0.41,P =0.05) and lissamine green conjunctival staining (r =-0.56,P =0.01 ; r =-0.37,P =0.04 ; r =-0.47,P =0.00).Conclusions Anterior segment module of OCT is an effective approach to the measurement of tear meniscus.The measuring outcomes of anterior segment of OCT are associated with dry eye-related signs.

Evaluation of treating mild ametropic amblyopia by refractive correction alone / 中华全科医师杂志

A total of 102 cases (204 eyes) with mild ametropic amblyopia underwent refractive correction without any vision training.After wearing glasses,visual acuity was examined every 3 months during a follow-up period of 12 months.After wearing glasses 12 months,201 eyes (98.53％) were treated effectively,175 eyes (85.78％) cured basically and 3 eyes (1.47％) became invalid.The changes of visual acuity were satisfactory(P ＜0.01).The difference of visual acuity between every two observation timepoints were satisfactory(P ＜0.01).Treating mild ametropic amblyopia by refractive correction alone is both simple and effective.And it has an excellent compliance and a low cost.

Clinical study of the treatment of lid-wiper epitheliopathy / 眼科研究

Objective Current research proposed that lid-wiper epitheliopathy may be a early symptom of dry eye.At present,there are seldom studies on lid-wiper epitheliopathy in both home and abroad.This study was to investigate the effect of artificial tears without antiseptic in the treatment of lid-wiper epitheliopathy and discuss the method of treatment of lid-wiper epitheliopathy. MethodsThis is a case-observative study.Seventy patients with lid-wiper epitheliopathy and with negative results in tear film break-up test,SchirmerⅠtest and corneal fluorescine staining were enrolled in the Peking University First Hospital during September 2006 and June 2008.The treatment group included 54 eyes of 54 patients who received topically free-antiseptic artificial tears (dextran 70 eye drops) four times per day for two weeks,and the control group included 16 eyes from 16 patients who were not treated.Dry Eye Questionnaire were taken from the patients before the administration of drug and 2 weeks after treatment.Fluorescein and Lissamine green double-staining was used before and after treatment for the evaluation of lid-wiper epitheliopathy.The disease was graded into 0 (absence) to 3(severe),and the symptoms and dye were scored following the Standard Patient Evaluation of Eye Dryness (Korb criteria).Informed consent and good compliance were obtained before initial and during the therapy duration. ResultsIn the treatment group,the scores of symproms and staining were significantly different between before and after administration of drug (12.91±2.55 vs 2.78±2.27 in symptom,t=22.70,P＜0.05;1.79±0.78 vs 0.19±0.31 in dye,Z=-6.40,P＜0.05),indicating the symptoms and dye results were obviously improved after therapy.In the control group,no significant differences were found in the symptom score and dye score in the corresponding time period (12.63±2.60 vs 12.94±2.11,t=-1.10,P＞0.05 in symptom;1.97±0.74 vs 1.98±0.72,Z=-0.58,P＞0.05 in dye).According to the grade of disease,the magnitude of the staining after treatment was considerably improved in comparison with before treatment (Z_1=-3.47 for mild,Z_2=-4.04 for moderate,Z_3=-3.74 for severe),showing statistically significant differences between them (P＜0.05).ConclusionThe use of artificial tears is an efficacious treatment for treating lid wiper epitheliopathy.The topicaly utilization of artificial tears can alleviate the symptoms and pathological changes of lid wiper epitheliopathy.

Stress on recognition and perioperative management of dry eye after LASIK / 眼科

Dry eye is the most common complication after laser in situ keratomileusis(LASIK). Attention should focus on screening of dry eye before LASIK, decreasing risk factors of surgical manipulation and topical drugs effect on dry eye. Proper management before, during and after LASIK can minimize dry eye. (Ophthalmol CHN, 2006, 15:154-155 )

Association between symptoms and signs of dry eye with Sjgren syndrome / 眼科

Objective To analyze the characteristics of ocular symptoms of Sjgren syndrome and to examine the relation between signs and symptoms.Design Prospective case series.Participants 36 patients with Sjgren syndrome diagnosed by rheumatisms.Methods A self-designed questionnaire was used to investigate 4 symptoms of patients including dryness,grittiness,soreness or irritation,burning or watering.A series of clinic tests were completed as follows:break-up time,fluorescein corneal staining,lissamine green conjunctival staining,Schirmer I test.The positive rate of such symptoms was calculated.The consistency of the symptoms and signs were compared.Main Outcome Measures Break-up time,fluorescein corneal staining,lissamine green conjunctival staining,Schirmer I test.Results Patients with Sjgren syndrome were marked by ocular symptoms.There were efficient statistically significant correlations between grittiness and fluorescein corneal staining,lissamine green conjunctival staining,break-up time(P

Systemic diseases in pediatric dry eye should not be overlooked / 眼科

Pediatric dry eye can occur associated with congenital,autoimmune,and inflammatory disorders.It is often misdiagnosed and untreated because of children's inability to participate in the assessment of subjective symptoms,also difficulty to be examined and unawareness of dry eye.So,it is necessary to pay more attention to dry eye in children.Etiology and characteristics of dry eye in children should be explored and understood.Multidisciplinary approaches of diagnose and treatment should be required.

Changes of tear lipid layer and treatment of evaporative dry eye / 眼科

The preocular tear film has recently been described as a bilaminar structure,including lipid layer and aqueous/mucin gel layer.The lipid layer has two phases,a relatively thick outer layer,containing nonpolar lipids such as wax esters,sterol esters,hydrocarbons, and triglycerides;and a thin polar inner layer,predominantly consisting of phospholipids.It s confirmed that there are differences in meibomian fatty acid composition between healthy and evaporative dry eye patients.Thus,therapies targeted at replenishing or stabilizing the lipid layer are key points to the treatment of evaporative dry eye,either as monotherapy or in conjunction with therapies designed to enhance aqueous production.

Collagen crosslinking with ultraviolet A-light and riboflavin—hope of keratoconus / 眼科

Collagen crosslinking by ultraviolet A-light and riboflavin is an effective means for increasing corneal rigidity and preventing the progression of keratoconus.Visual acuity can be improved slightly.The maximum effect of the treatment locates in the anterior 300-340?m of the cornea.No statistically significant change is found for endothelial cell density.With more long-term research, prophylactic treatment of keratoconus at the early stage might become possible,preventing the development of keratoconus and additional refractive correction can be realized.

Avoiding misdiagnosis of corneal endotheliitis / 眼科

It is not uncommon for corneal endotheliitis in clinic.Misdiagnosis of the disease was often happened because of the insufficient knowledge on it and lacking of specific examine methods.It is the most important method for avoiding misdiagnosis of corneal endotheliitis to recognize its clinic features and detailed inquiring case history.