Objective Response surface methodology ( RSM ) was applied to optimize the ultrasonic extraction conditions for flavonoids from Coreopsis tinctoria Nutt. Methods The influence factors of ultrasonic extraction were evaluated using the Box-Behnken central component experiments and analyzed by RSM. Results The optimum extraction conditions were confirmed as follows:extraction time 30. 0 min, ratio of liquid to solid 21∶1, concentration of ethanol 60%. The yield of flavonoids under this condition was (4.65±0.036)% (n=3). Conclusion The flavonoids could be extracted with stability and higher yield from Coreopsis tinctoria Nutt under optimized conditions.

Objective: To explore the relationship between intra-operative blood product transfusion and post-operative prognosis in children with pediatric open heart surgery by cardiopulmonary bypass (CPB).
Methods: A total of 1028 consecutive pediatric patients received the open heart surgery by CPB in our hospital were retrospectively studied. Uni- and multivariate Logistic regression analysis were conducted to analyze the relationship between intra-operative blood product transfusion and post-operative in-hospital death and complication rates.
Results: There were 45/1028 (4.4%) of patients died, 143 (13.9%) with low cardiac output syndrome, 43 (4.2%) received dialysis, 26 (2.5%) with sustained pulmonary failure, 17 (1.7%) with infection, and 28 (2.7%) developed neurologic complications. Multivariate Logistic regression analysis indicated that duration and the lowest temperature of CPB, 24-hour post-operative pediatric risk of mortality (PRISM-III) score and intra-operative transfusion amount of RBC > median (20.3 ml/kg) were the independent risk factors for post-operative in-hospital death. Congenital heart disease (CHD) with pre-operative cyanosis, duration of CPB, 24-hour post-operative PRISM-III score, 6-hour post-operative mediastinal drain loss and intra-operative transfusion amount of RBC > 20.3 ml/kg were the independent risk factors for post-operative complication occurrence.
Conclusion: Large volume of RBC transfusion in the open heart pediatric surgery with CPB may increase the risk of post-operative in-hospital death and complication occurrence, reducing RBC transfusion might be improving the post-operative prognosis in CHD patients.

ObjectiveTo study the expression of microRNA-21 ( miR-21 )in serum of patient with diffuse large B cell lymphoma (DLBCL) and DLBCL cell lines and validate the significance of miR-21 in early diagnosis,genotyping and prognosis estimates of DLBCL.MethodsmiR-21 expression were detected by fluorescent quantity polymerase chain reaction (FQ-PCR)in 9 lymphoma cell lines (OCI-Ly1,OCI-Ly3,OCI-Ly4,OCI-Ly7,OCI-Ly8,OCI-Ly10,OCI-Ly18,OCI-Ly19 and HBL),the serum from DLBCL patients (n =62) and health controls (n =50 ).Kaplan-Meier survival analysis was carried out during the relapsefree survival period of DLBCL patients to explore the relationship between the prognosis and microRNA expression level.ResultsReal time FQ-PCR result indicated that miR-21 expression was higher in DLBCL cell lines than that in normal B cells (BC).miR-21 expression in normal B cell and 9 DLBCL cell lines separately were 1.04 ± 0.02,2.30 ± 0.35,237.97 ± 56.19,5.27 ± 0.83,3.40 ± 0.30,11.22 ± 2.70,133.55 ± 16.78,6.63 ±0.24,4.91 ±0.37 and 81.59 ±6.64.Compared with BC,the expression of miR-21 were higher in all 9 DLBCL cell lines ( t =7.3,13.7,21.0,6.2,8.8,13.6,6.5,39.5,18.1 ;P ＜ 0.01 ).miR-21 expression segregates with specific molecular subgroups of DLBCL The expression was higher in the ABC type cell lines (OCI-Ly3,OCI-Ly10,HBL) than GCB type cell lines (OCI-Ly1,OCI-Ly4,OCI-Ly7,OCI-Ly8,OCI-Ly18,OCI-Ly19;t =11.18,P ＜ 0.01 ).Consistent with the cell line models,miR-21 expression levels were higher in serum from DLBCL patients [21.38 (10.26-45.21 )] than from controls [1.87 ( 1.05-3.97 ),U =168,P =0.000],and the levels were higher in DLBCL cases with an ABC-type [28.68 ( 14.92-98.44 )] than those in GCB-type [18.30 ( 7.32-33.46 ),U =336,P =0.043].MiR-21 expression levels were different in sera from different clinical stage DLBCL patients.The miR-21 level in serum of patients with subgroup ABC and subgroup GCB in stage Ⅰ and Ⅱ were 47.49( 25.65-295.41 ) and 24.74( 16.08-50.38) respectively and in stage Ⅲ and Ⅳ were 16.66 ( 5.35-44.30 ) and 11.96 ( 4.10-21.05) respectively.The levels were higher in DLBCL cases withⅠ -Ⅱ stage than those with Ⅲ-Ⅳ stage (U =62,P =0.013 in GCB type; U =53,P =0.014 in ABC type).Moreover,compare with relapse-free survival in DLBCL patients,high miR-21 expression was associated with well prognosis ( U =259,P =0.035).ConclusionsMiR-21 is high expression in DLBCL cell lines and DLBCL patients serum.miR-21 level in sera from DLBCL patients is associated with clinical stage,molecular subgroup and prognosis estimates.MiR-21 may serve as a new biomarker to early detection,genotyping and prognosis estimates of DLBCL.

We investigated the roles of the crude antigen(CA) of Clonorchis sinensis and excretory secretory products (ESPs) in the polarization of Th1 and Th2 cells.Bone marrow-derived cells were generated from BALB/c mice and isolated into immature DCs;immature DCs were then treated with either CA (CA stimulated group),ESPs (ESPs stimulated group),LPS (positive control group) or PBS (negative control group) for 24 hours.Then the CD4+T cells were isolated from mouse spleen by using anti mouse-CD4 Microbeads,and further cocultured with stimulated DCs for another 72 hours.The purities of DCs and CD4+ T cells were evaluated by flow cytometry and the expressing levels of T-bet mRNA and GATA-3 mRNA were detected by real-time PCR.ELISA was used to detect the levels of IFN-γ and IL-4 cytokines in the supernatant.mRNA levels of T-bet and GATA-3 in the ESPs group were higher than those in PBS-stimulated group (P＜0.05).The concentrations of IFN-γ and IL-4 cytokines in the culture were increased in the ESPs group,compared with PBS stimulated group(P＜0.05).IFN-γ but not IL-4 was increased in CA group (P＜0.05).The results implied that CA might play a role in Th1 type immune response,and ESPs likely play roles in both Th1 and Th2 immune responses.

Objective To investigate the effects of cholesterol-lowering agents on the proliferation, stemness characters, migration, invasion, and neutrophil extracellular traps formation (NETs) formation in liver cancer cells. Methods ASPP2 or HMGCR gene was knocked down in mouse liver cancer cell Hepa1-6 to establish cells with high or low cholesterol, respectively. Simvastatin and berberine were used to reduce cholesterol synthesis. CCK-8 and plate cloning assays were conducted to detect the proliferation ability of liver cancer cells. Sphere formation assay and qRT-PCR were used to analyze the stemness character and expression of related genes. Wound-healing assay and Transwell assay were used to analyze the ability of cell migration and invasion. Immunofluorescence staining was carried out to analyze the effect of lipid-lowering agent on NETs formation. Results Cholesterol-lowering agents significantly inhibited the proliferation and stemness-related gene expression of Hepa1-6 cells (P < 0.001), significantly inhibited the migration and invasion of Hepa1-6 cells (P < 0.001), and significantly inhibited the neutrophil-induced invasion and formation of NETs (P < 0.001). Conclusion Cholesterol-lowering agents suppress the proliferation and invasion via inhibiting the stemness characters and NETs formation in liver cancer cells. It is a potential strategy for the treatment of liver cancer metastasis.

Objective To provide a comprehensive reference index for different mouse models of herpes simplex virus 1 (HSV-1) infection by investigating the related clinical manifestations, pathological features and characteristics of viral distribution in tissues and organs of BALB/c mice infected with different HSV-1 strains by using different strategies.Methods Acute infection models were established by challenging BALB/c mice at age three or six weeks with HSV-1 17+ and McKrae strains via intranasal and corneal administrations.Correspondingly, chronic infection models were established with BALB/c mice through subcutaneous and foot pad injections.Results Although all experimental mice showed trichiasis and roachback, there were differences in weight and fatality rate among different groups.Results of the quantitative PCR detection indicated that the proliferation of HSV-1 in the nervous tissues (brain, spinal cord, trigeminal ganglion) varied among different groups.The pathological examination indicated that in the acute infection groups, significant pathological changes only occurred in the brain tissues, while in the chronic infection groups, pathological injuries only occurred in the trigeminal ganglia.Although a key index latency-associated transcript (LAT) was not detected in the trigeminal nerve tissues of mice in the chronic infection groups, co-culturing the tissues with Vero cells resulted in infectious lesions in the cells.Conclusion This study indicates that there are significant differences in weight and fatality rate among different BALB/c mouse models of HSV-1 infection.Varied replication dynamics of HSV-1 were observed in different tissues or organs of the BALB/c mice in different groups.Therefore, different indexes should be adopted to evaluate different HSV-1 infection models.

In order to study effects of ginseng on the metabolism of drug belong to CYP3A4 substrate, screening of pregnane X receptor activation from ginsenosides was performed by reporter assay. Based on PXR-CYP3A stable translation cell lines, 13 ginsenosides were screened for pregnane X receptor activation by reporter assays, and RIF as the positive control. The effect of ginsenosides Rg1 onCYP3A4 mRNA expression was also investigated by RT-PCR. The PXR-CYP3A stable translation cell lines had good response to RIF, and the EC50 is 2.51 micro mol x L(-1). When the condition of final concentration was 10 micromol x L(-1), ginsenoside F2 and protopanaxatriol had moderate inductive effects on PXR. Panaxotriol, Rg2, pseudoginsenoside F11, Rg1, ginsenoside and Rb3 had inhibitory effects on PXR. Ginsenoside Rf1, Rg3, Rh2 and protopanaxdiol had no obvious effects on PXR. Rg1 down-regulated CYP3A4 mRNA expression in a concentration-dependent manner. Activation of pregnane X receptor by ginsenosides may influence the metabolism of drug belong to CYP3A4 substrate, and cause ginseng-drug interactions.

Objective To explore heterogeneous subtypes of psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation and the characteristics differences of different types of children after liver transplantation. Methods Seven hundred and forty-one children who underwent living-related liver transplantation were enrolled. The self-designed general information questionnaire, Chinese version of 5-Item World Health Organization Well-Being Index (WHO-5) and the parent-report version of the Strengths and Difficulties Questionnaire (SDQ) were filled out by their guardians. The scores of five dimensions of SDQ were used as the manifest variables of the model. The classification model of psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation was constructed by latent profile analysis. The latent categories of psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation were analyzed. The influencing factors of latent categories were analyzed by univariate analysis and logistic regression model. Results There were three latent categories of psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation, including peer communication problem group (n=302), psychological and behavioral adaptation group (n=145) and psychological and behavioral adjustment difficulty group (n=294). The first two groups were merged into the psychological and behavioral health group (n=447), which had significant differences in the five dimensions and the total score of difficulties of SDQ compared with the psychological and behavioral adjustment difficulty group (n=294) (all P<0.001). Logistic regression analysis showed that age≤5 years old, primary disease of non-cholestatic liver disease, stem family were the risk factors for psychological and behavioral adjustment difficulties in pediatric recipients after liver transplantation. Female gender, high education levels of parents and high WHO-5 score of guardians were the protective factors for psychological and behavioral adjustment difficulties in pediatric recipients after liver transplantation (all P<0.05). Conclusions The psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation are heterogeneous. Medical staff should pay extensive attention to different characteristics of pediatric recipients after liver transplantation with different psychological and behavioral adaptation categories and adopt targeted screening and intervention strategies, aiming to improve psychological and behavioral adaptation outcomes of pediatric recipients after liver transplantation.

We analyzed the whole genome coding sequence of Volvariella volvacea to study the pattern utilization of codons by Codon W 1.4.2. As results, 24 optimal codons were identified. Moreover, the frequency of codons usage was calculated by CUSP program. We compared the frequency of codons usage of V. volvacea with other organisms including 6 modal value species (Homo sapiens, Saccharomys cerevisiae, Arabidopsis thalian, Mus musculus, Danio rerio and Drosophila melanogaster) and 4 edible fungi (Coprinopsis cinerea, Agaricus bisporus, Lentinula edodes and Pleurotus ostreatus). We found that there were less differences in 3 edible fungi (excluding Pleurotus ostreatus) than 6 modal value species, comparing with the frequency of codons usage of V. volvacea. With software SPSS16.0, cluster analysis which showed differences in the size of codon bias, reflects the evolutionary relationships between species, which can be used as a reference of evolutionary relationships of species. This was the first time for analysis the codon preference among the whole coding sequences of edible fungi, serving as theoretical basis to apply genetic engineering of V. volvacea.
Agaricales ; genetics ; Animals ; Arabidopsis ; genetics ; Cluster Analysis ; Codon ; DNA, Fungal ; genetics ; Drosophila melanogaster ; genetics ; Humans ; Mice ; Saccharomyces cerevisiae ; genetics ; Software ; Volvariella ; genetics ; Zebrafish ; genetics

Objective:To explore the effects of bariatric metabolic surgery on body composition.Methods:The retrospective cohort study was conducted. The clinicopathological data of 66 patients with metabolic diseases who were admitted to the Third Xiangya Hospital of Central South University from January 2013 to December 2014 were collected. There were 42 males and 24 females, aged (40±11)years, with a range from 17 to 63 years. Of the 66 patients, 27 undergoing laparoscopic sleeve gastrectomy (LSG) and 39 undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) were allocated into LSG group and LRYGB group, respectively. The body composition of all patients was determined by dual-energy X-ray absorptiometry at preoperation and postoperative 6 months. Observation indicators: (1) the changes of anthropometric parameters, glucolipid metabolism, body fat mass percentage (BF%) and the ratio of Android BF% and Gynoid BF% (A/G ratio) from preoperation to postoperative 6 months; (2) the changes of whole and local body composition from preoperation to postoperative 6 months; (3) analysis of the correlation between BF% and anthropometric parameters, glucolipid metabolism. (4) Follow-up. Follow-up was conducted using outpatient or hospitalization examination to detect the changes of body composition at the time of postoperative 6 month. The follow-up time was up to July 2015. Measurement data with normal distribution were represented as Mean± SD, paired-samples t test was used for intra-group comparison, and independent-samples t test when baseline data were consistency or covariance analysis when baseline data were not consistency was used for inter-group comparison. Measurement data with skewed distribution were represented as M ( P25, P75), and comparison between groups was analyzed using Wilcoxon signed rank test. The correlation test was undertaken with the Pearson bivariate analysis. Results:(1) The changes of anthropometric parameters, glucolipid metabolism, BF% and A/G ratio from preoperation to postoperative 6 months: for patients in the LSG group, the body mass, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), diastolic blood pressure (DBP), systolic blood pressure (SBP), fasting plasma glucose (FPG), HbA1c, high density lipoprotein cholesterol (HDL-C), triglyceride (TG), whole BF%, arms BF%, legs BF%, trunk BF%, Android BF%, Gynoid BF% and A/G ratio at preoperation and postoperative 6 months were (102±17)kg, (37±5)kg/m 2, (118±14)cm, 1.01±0.06, (94±14)mmHg(1 mmHg=0.133 kPa), (137±15)mmHg, (8.1±4.2)mmol/L, 7.3%±2.4%, (1.11±0.26)mmol/L, 2.14 mmol/L(1.73 mmol/L, 2.59 mmol/L), 40%±6%, 46%±10%, 36%±8%, 42%±6%, 45%±6%, 37%±7%, 1.23±0.18 and (82±15)kg, (29±4)kg/m 2, (101±13)cm, 0.95±0.08, (76±10)mmHg, (118±16)mmHg, (7.2±1.2)mmol/L, 5.4%±0.8%, (1.26±0.32)mmol/L, 1.21 mmol/L(0.88 mmol/L, 1.55 mmol/L), 36%±8%, 41%±9%, 34%±10%, 38%±8%, 41%±8%, 35%±10%, 1.20±0.17, respectively. There was no significant difference in the intra-group comparison of the Gynoid BF% and A/G ratio ( t=1.903, 1.730, P>0.05) and there were significant differences in the intra-group comparison of the rest of above indicators ( t=12.748, 13.283, 9.013, 3.804, 6.031, 6.226, 2.393, 4.287, -2.900, 3.193, 2.932, 5.198, 2.167, 3.357, 3.116, P<0.05). For patients in the LRYGB group, the body mass, BMI, WC, WHR, DBP, SBP, FPG, HbA1c, HDL-C, TG, whole BF%, arms BF%, legs BF%, trunk BF%, Android BF%, Gynoid BF% and A/G ratio at preoperation and postoperative 6 months were (80±12)kg, (28±4)kg/m 2, (98±9)cm, 0.96±0.05, (85±10)mmHg, (134±17)mmHg, (8.6±2.8)mmol/L, 8.3%±1.7%, (1.13±0.26)mmol/L, 2.06 mmol/L(1.15 mmol/L, 3.30 mmol/L), 30%±8%, 29%±11%, 23%±9%, 37%±7%, 40%±7%, 29%±8%, 1.42±0.26 and (69±9)kg, (24±3)kg/m 2, (91±8)cm, 0.93±0.05, (80±9)mmHg, (129±18)mmHg, (7.4±1.8)mmol/L, 7.0%±1.5%, (1.18±0.29)mmol/L, 1.29 mmol/L(0.85 mmol/L, 2.02 mmol/L), 25%±8%, 23%±12%, 20%±9%, 29%±9%, 32%±10%, 25%±9%, 1.29±0.25, respectively. There was no significant difference in the intra-group comparison of the SBP and HDL-C ( t=1.733, -1.073, P>0.05) and there were significant differences in the intra-group comparison of the rest of above indicators ( t=10.525, 10.200, 7.129, 2.887, 2.805, 2.517, 3.699, 2.608, 7.997, 8.018, 6.029, 8.342, 8.069, 5.813, 6.391, P<0.05). There were significant differences in DBP, SBP, HbA1c, trunk BF%, Android BF% and A/G ratio at postoperative 6 months between LSG group and LRYGB group ( F=6.408, t=2.641, F=20.673, 5.140, 5.735, 4.714, P<0.05). (2) The changes of whole and local body composition from preoperation to postoperative 6 months: for patients in the LSG group, the whole fat mass, muscle mass, fat-free mass at preoperation and postoperative 6 months were (38.74±9.68)kg, (57.71±11.62)kg, (60.14±11.95)kg and (26.64±8.29)kg, (48.65±13.80)kg, (51.00±14.27)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=5.256, 5.413, 5.315, P<0.05); the arms fat mass, muscle mass, fat-free mass were (5.19±1.67)kg, (5.78±1.58)kg, (6.10±1.64)kg and (3.73±1.19)kg, (5.10±1.53)kg, (5.43±1.57)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=7.564, 5.405, 5.363, P<0.05); the legs muscle mass and fat-free mass were (19.05±4.19)kg, (19.93±4.35)kg and (15.93±4.71)kg, (16.81±4.87)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=5.623, 5.568, P<0.05); the trunk fat mass and fat-free mass were (21.93±4.90)kg, (29.7±5.94)kg and (14.69±4.79)kg, (24.78±7.02)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.903, 5.421, P<0.05); the Android fat mass and fat-free mass were (4.16±1.19)kg, (5.01±1.12)kg and (2.57±0.90)kg, (3.83±1.20)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.288, 7.637, P<0.05); the Gynoid fat mass and fat-free mass were (5.51±1.42)kg, (9.27±1.86)kg and (3.85±1.16)kg, (7.65±2.31)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=7.461, 5.672, P<0.05); the skeletal muscle index were (8.86±1.38)kg/m 2 and (7.49±1.71)kg/m 2, respectively, showing a significant differences in the intra-group comparison ( t=5.724, P<0.05). For patients in the LRYGB group, the whole fat mass, muscle mass, bone mineral content, fat-free mass at preoperation and postoperative 6 months were (23.58±7.80)kg, (51.76±8.35)kg, (2.55±0.48)kg, (54.31±8.63)kg and (16.88±6.86)kg, (49.41±7.70)kg, (2.47±0.50)kg, (51.88±8.05)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=9.001, 3.974, 4.354, 4.075, P<0.05); the arms fat mass were (2.72±2.37)kg and (1.73±1.02)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=3.470, P<0.05); the legs fat mass, muscle mass, fat-free mass were (5.21±2.46)kg, (16.68±3.50)kg, (17.60±3.66)kg and (4.01±2.12)kg, (15.63±2.90)kg, (16.54±3.05)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=6.592, 3.372, 3.319, P<0.05); the trunk fat mass were (14.87±4.11)kg and (10.38±4.00)kg, respectively, showing a significant difference in the intra-group comparison of the above indicators ( t=8.431, P<0.05); the Android fat mass and fat-free mass were (2.61±0.86)kg, (3.96±0.87)kg and (1.81±0.79)kg, (3.78±0.67)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.032, 2.153, P<0.05); the Gynoid fat mass and fat-free mass were (3.14±1.17)kg, (7.89±1.58)kg and (2.44±0.96)kg, (7.43±1.26)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=6.112, 3.207, P<0.05); the skeletal muscle index were (8.04±1.22)kg/m 2 and (7.43±1.13)kg/m 2, respectively, showing significant differences in the intra-group comparison ( t=4.953, P<0.05). There were significant differences in whole muscle mass, whole fat-free mass, arms fat mass, legs muscle mass, legs fat-free mass, trunk fat-free mass, Android fat-free mass, Gynoid fat-free mass and skeletal muscle index at postoperative 6 months between LSG group and LRYGB group ( F=13.846, 13.614, 23.696, 7.100, 7.127, 15.243, 16.921, 8.625, 5.497, P<0.05). (3) Analysis of the correlation between BF% and anthropometric parameters, glucolipid metabolism: the whole BF% of 66 patients was positively correlated with body mass, BMI, WC and WHR ( r=0.405, 0.663, 0.625, 0.331, P<0.05); the arms BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.432, 0.682, 0.639, 0.309, P<0.05); the legs BF% was positively correlated with body mass, BMI and WC ( r=0.366, 0.646, 0.564, P<0.05); the trunk BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.332, 0.560, 0.554, 0.335, P<0.05); the Android BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.327, 0.537, 0.543, 0.336, P<0.05); the Gynoid BF% was positively correlated with BMI and WC ( r=0.561, 0.488, P<0.05), and negatively correlated with FPG ( r=-0.491, P<0.05); the A/G ratio was negatively correlated with BMI ( r=-0.334, P<0.05), and positively correlated with FPG ( r=0.506, P<0.05); the skeletal muscle index was positively correlated with body mass, BMI, WC and WHR ( r=0.757, 0.641, 0.609, 0.519, P<0.05), and negatively correlated with HDL-C ( r=-0.369, P<0.05). (4) Follow-up: 66 patients were followed up at the time of postoperative 6 month. Conclusions:Both LSG and LRYGB significantly change body composition. LRYGB is superior to LSG in reducing trunk BF% and Android BF%. The effects of the two surgical methods on fat mass and bone mineral content are similar. LSG lead to a more significant decrease in whole muscle mass, and LRYGB lead to a more significant decrease in legs muscle mass and skeletal muscle index.