Aim: To study the pharmacokinetic effects of salvianolic acid B( Sal B) on danshensu( DSS) in Danshen injection in rats. MGthod: Following the intravenous administration of Danshen injection and Danshen injection added with Sal B to rats, the plasma kinetic study, tissue distribution and urine excretion were studied. The plasma kinetic study was also investigated by giving DSS and DSS in combination with Sal B to rats. Plasma, tissue and urine drug levels of danshensu were analyzed by LC-MS. Results: Compared with danshensu given alone, no significant difference of the pharmacokinetic behavior of danshensu was found when danshensu was given in combination with salvianolic acid B. However, compared with Danshen injection given alone, the pharmacokinetic behavior of danshensu changed remarkably when Danshen injection was given in combination with salvianolic acid B which might be caused by the decrease of DSS in kidney distribution and urine excretion. Conclusion: The pharmacokinetic effects of salvianolic acid B on danshensu depend on the existence of multiple components in Danshen injection. Results suggest that the pharmacokinetic interactions of the multiple components are closely related to the integrity of herbal medicines.

Objective To study the effects of Poly(I:C) on lung adenocarcinoma A549 cells viability and illuminate the mechanism of Poly (I:C)-induced apoptosis in A549 cells.Methods A549 cells were transfected with the complex of Poly(I:C) and lipofectamine 3000.The viability of A549 cells was tested by methyl thiazolyl tetrazolium (MTF) method.The apoptotic cells were tested by flow cytometry.The caspase proteins were tested by Western blotting and the expressions of interferon-β (IFN-β) and CXCL-10 were assayed by real-time PCR.After employing the pan-caspase inhibitor Z-VAD-FMK and caspase-8 inhibitor Z-IETD-FMK,the variation of Poly (I:C) proapoptosis in A549 cells was observed.RNA interfering experiments were employed to knock down melanoma differentiation related antigen 5 (MDA5) or retinoic acidinduced gene Ⅰ (RIG-Ⅰ),and the above indexes were tested.Results The viability of A549 cells was significantly reduced to 74.92％ ±--6.24％ after 200 ng/ml Poly (I:C) transfection compared with that before transfection (95.32％ ± 3.05％,t =2.883,P =0.041).The apoptotic rates induced by 100,200,400 ng/ml Poly(I:C) were 9.97％-± 0.88％,23.63％-± 1.41％,32.57％-± 2.39％,respectively.All of them were higher than that in the control group (0.74％-± 0.15％),with significant differences (t =4.489,P =0.002;t =11.616,P =0.000;t =16.932,P =0.000).Besides,the death receptor pathway proteins such as TNF-related apoptosis inducing ligand (TRAIL),cleaved-caspase-8 and cleaved-caspase-3 increased obviously.MDA5/RIG-Ⅰ pathway was also activated dramatically and the expressions of IFN-β,CXCL-10 were significantly up-regulated.The apoptotic rates reduced to 3.17％ ± 0.66％,5.35％ ± 0.64％ with pancaspase inhibitor Z-VAD-FMK and caspase-8 inhibitor Z-IETD-FMK pretreatment,compared with the control group (15.87％ ±0.93％),and the differences were statistically significant (t =8.643,P =0.001;t =6.824,P =0.002).Moreover,the expressions of TRAIL,IFN-β and CXCL-10 induced by Poly (I:C) were inhibited with MDA5 or RIG-Ⅰ depletion.Conclusion Poly(I:C) can reduce the survival rate of A549 cells and promote the apoptosis mainly by activating the death-receptor pathway mediated by MDA5/RIG-Ⅰ probably,which may involve in IFN-β,CXCL-10.

Objective:To investigate the risk factors of central lymph node metastasis (CLNM) in cN0 paillary thyroicl microcarcinoma (PTMC) and to establish a nomogram model for predicting the probability of cN0 PTMC CLNM.Methods:The clinicopathological data of 192 patients with cN0 PTMC admitted to the Department of General Surgery of the Second Hospital of Lanzhou University from Aug. 2016 to Aug. 2020 were retrospectively analyzed. There were 41 males and 151 females, 50 with CLNM and 142 without CLNM. The patients were divided into 2 groups according to the presence or absence of pathologically confirmed CLNM. Patient’s age, gender, tumor diameter, multiple, with Hashimoto’s disease, with nodular goiter, with or without near the posterior dorsal membrane, aspect ratio >1, with or without extratumoral infiltration, with or without lymphadenopathy, TSH levels, and TG levels were statistically analyzed. Pearson chi-square test was used to analyze the count data of hypothesis test, and the R language software package was used for Logistic multivariate analysis. The entry conditions were screened by stepwise regression to establish a nomogram prediction model, and the Bootstrap method was used for model verification. P<0.05 was considered statistically significant. Results:Multivariate logistic analysis showed that extratumoral invasion ( P=0.032) , presence of lymphadenopathy ( P=0.010) , and TG>68 μg/L ( P=0.007) were risk factors for central lymph node metastasis. The optimal model was established by stepwise regression. The factors included tumor diameter ≥0.5 cm, nodular goiter, extratumoral invasion, lymphadenopathy and TG>68 μg/L (AIC: 212.27) . The nomogram model was established according to the above risk factors. The consistency index (c-index) was 0.711. The results of calibration graph drawing and internal and external validation demonstrated its good consistency and applicability. Conclusion:Extratumoral invasion, lymphadenopathy, and TG>68 μg/L are risk factors for cN0 PTMC CLNM, and the nomogram established in the study can effectively predict the CLNM rate in patients with cN0PTMC and contribute to clinicians’ diagnosis and treatment decisions.

Aim To identify alteration in key molecular components related to memory formation and insulin signaling in the hippocampus after rosiglitazone was in-jected into the ob/ob mice to test whether cognitive dysfunction was pharmacologically reversed by regula-tion of rosiglitazone. Methods The age-matched mice were divided into three groups ( n=18 ): Saline-trea-ted WT mice ( WT-Saline);Saline-treated ob/ob mice ( ob/ob-Saline) and RSG-treated ob/ob mice ( ob/ob-RSG) through intraperitoneal injection of rosiglitazone ( RSG) . The random glucose levels were measured for 10 days during the intraperitoneal injection period. No-vel object recognition was performed before mice were sacrificed. Western blot was implemented to evaluate the following proteins: BACE1, p-Tau, p-IRS1,IRS1, p-Akt and Akt in hippocampal tissues. The Aβ1-40 levels were detected by ELISA Kit. Results The random blood glucose levels were significantly re-duced in ob/ob-RSG compared with ob/ob-saline. RSG treatment led to an increase in hippocampus-de-pendent cognition of ob/ob mice according to the novel object recognition. The proteins levels of BACE1, p-Tau and Aβ were lowered in RSG-treated ob/ob mice. Furthermore, RSG treatment up-regulated hippocampal p-IRS1/IRS1 and p-Akt/Akt ratio. Conclusion Ros-iglitazone ameliorates cognitive deficits in ob/ob mice through up-regulating insulin signaling pathways in the hippocampus.

Objective To analyze the etiologic spectrum of hand, foot and mouth disease (HFMD) and the molecular characteristics of coxsackievirus A10 (CVA10) strains isolated in Qingdao from year 2010 to 2012.Methods Throat swab specimens were collected from patients with HFMD to detect to-tal enteroviruses ( EVs) , EV71 and CVA16 strains by multiplex real time RT-PCR.The EV-positive speci-mens were further detected by a semi-nested RT-PCR to amplify the sequence of viral genes encoding VP1. The serotypes of EVs were identified based on the sequences of genes encoding VP1.The full-length gene se-quences encoding VP1 of CVA10 isolates were amplified and sequenced. The phylogenetic analysis was con-ducted by using MEGA5.0 software package.Results A total of 1919 outpatients with mild HFMD and 1336inpatients with serious HFMD were recruited in this study .CVA16 strains were the predominant patho-gen for outpatients in year 2010 ( prevalence rate of 53%) and 2012 ( prevalence rate of 73%) .EV71 strains were the predominant pathogen for outpatients in year 2011 ( prevalence rate of 78%) and inpatients in year 2010 ( prevalence rate of 70%) and 2011 ( prevalence rate of 86%) . Some serotypes other than CVA16 or EV71 were the predominant pathogens for inpatients in year 2012 ( prevalence rate 44%) . CVA10 strains were identified in 12 patients with HFMD in year 2010and 17 patients with HFMD in 2012. The full-length gene sequences encoding VP1 of 23 CVA10 isolates were successfully amplified and se-quenced.The phylogenetic analysis showed that the 23 CVA10 isolates all belonged to genotype C and could be further divided into six clades.The genes encoding VP1 of the 23 CVA10 strains shared 97.3% to 1000.%homologies in amino acid sequences.The CVA10 isolates were also similar to their counterparts isolated from other regions during the same period.Conclusion CVA16 and EV71 strains were the preva-lent pathogens of HFMD in Qingdao from year 2010 to 2012, co-circulated with some other serotypes of EVs, especially CVA10 strains.The CVA10 strains belonged to genotype C and shared high homologies among them and their counterparts circulated in other regions during the same period.

Objective To explore the clinical significance of detecting serum levels of IL-6 and TNF-α in patients with intracranial hemorrhage.Methods The serum levels of IL-6 and TNF-α in different period were detected in patients with intracranial hemorrhage, by enzyme-linked immunosorbent assays (ELISA), and compared with those of healthy subjects (the control group).ResultsThe serum levels of IL-6, TNF-α in the severe and slight patients of study group on 1st, 3rd, 5th and 7th were signiifcantly higher than those in the control group (all withP<0.05). The serum levels of IL-6, TNF-α in the severe patients of study group were signiifcantly higher than those in slight patients of study group (all withP<0.05) on 5th and 7th. The serum levels of IL-6 and TNF-α in dead cases on 5th, 7th days admission were significantly higher than those in survival cases (P<0.05). The serum levels of IL-6 was positively correlated with TNF-α (r=0.721,P<0.05).Conclusion The detection of dynamically serum levels of IL-6 and TNF-α is of great clinical value for assessing the disease development therapeutic efifcacy and prognosis of brain injury patient with intracranial hemorrhage.

Objective To investigate the effect of sulforaphane on 1-methyl-4-phenylpyridinium (MPP +)-induced cell viability loss in cultured PC12 cells and to explore the possible mechanism.Methods MPP + induced damage in PC12 cells was prepared as oxidative damage model.Sulforaphane (0.5,1.O,2.5,5.0 and 10.0 μmol/L) was added in each group cell growth medium.Subsequent experiments were divided into 4 groups:(A) normal control group,(B) sulforaphane group,(C) MPP+ injury group,(D)sulforaphane pretreatment + MPP+ injury group.Cell viability was detected by MTT assay,and the sulforaphane pretreatment PC12 cell viability was observed in different concentrations.Flow cytometry was used to detect changes in the rate of apoptosis in different packet PC12 cells,and protein expression levels of nuclear factor erythroid2-related factor 2 (Nrf2),heme oxygenase (HO-1) and human NAD (P) H dehydrogenase,quinone 1 (NQO1) were detected by Western blot when the PC12 cells were incubated with sulforaphane (2.5 μmol/L) and (or) MPP+ (500 μmol/L) for 24 h in vitro.Results Compared to control group (cell survival rate was 98.70％),the survival percents of PC12 cells were significantly decreased in MPP+-treated group (58.16％).A significant difference was showed between group A and C (F =21.83,P ＜ 0.05),and the cell survival rate in group D was significantly improved.Compared to control group,the rate of apoptosis in MPP+ injury group was increased,and the rate of apoptosis after pretreatment of the sulforaphane was significantly reduced.Compared to MPP+ injury group,the levels of Nrf2,HO-1 and NQO1 protein expression were significantly increased in sulforaphane pretreatment group.Conclusion Sulforaphane have a protective effect against MPP+-induced PC12 cell model damage,and the protective effect may be achieved by activating the Nrf2-antioxidant response element pathway.

Objective To investigate the etiology spectrum of hand , foot and mouth disease ( HFMD) and to analysis the molecular characteristics of three predominant human enterovirus stains in Qingdao in 2013.Methods The total enterovirus (EV) strains and strains of EV71, CVA16 and CVA6 in throat swabs of HFMD cases were detected by using multiplex real time RT-PCR.The full-length of the viral VP1 genes of the EV strains were amplified and sequenced .The sequences were phylogenetically analyzed by using the MEGA5.0 software package .Results A total of 841 patients with mild HFMD and 107 patients with serious HFMD were recruited in this study and 64 .3%of them were positive for EV .The predominant pathogens were EV71 (44.8%), CVA6 (28.2%) and CVA16 (9.5%) in 2013.CVA6 replaced CVA16 as the second most common pathogen for HFMD , accounting for 42.7% of all pathogens in children aged less than 3 years and 22.2%of all pathogens in the serious patients .The proportions of CVA6 in the etiology spectrum showed a downtrend along with the increasing age of the patients (P<0.001).Phylogenetic analy-sis of the complete VP1 gene sequences showed that all of the EV 71 strains identified in this study belonged to the subgenotype C4 (evolutionary branch C4a) and all of the CVA16 strains belonged to the subgenotype B1 (evolutionary branches B1a and B1b).There were 6 genogroups (A to F) regarding to the VP1 gene of CVA6 and all of the CVA6 strains identified in this study belonged to genogroups A and D .Among the CVA6 strains isolated in Qingdao in 2013, 83.9% belonged to genogroup A, while the rest 16.1% belonged to genogroup D.66.7%of the CVA6 strains isolated in 2012 belonged to genogroup A, while the rest 33.3%belonged to genogroup D .All of the CVA6 strains isolated from year 2008 to 2011 in Qingdao belonged to genogroup D.Conclusion EV71, CVA6 and CVA16 were the prevalent pathogens responsible for the de-velopment of HFMD in Qingdao in 2013.The proportions of CVA6 strains in the etiology spectrum showed a downtrend with the increasing age in children .C4a was the major subtype of EV71 strains circulating in Qingdao in 2013, while B1a and B1b were the major subtypes of CVA16 strains.The pattern of endemic cir-culation of CVA6 strains showed a trend of changing from genogroup D to A from year 2008 to 2013 .

0.05)].Maternal serum concentrations of TG and LDL-C were significantly increased in DM group [(3.6?0.9)and(4.8?0.6)mmol/L] compared with GIGT group [(2.7?0.7)and(3.8?0.9)mmol/L] and GDM group [(2.9?0.7)and(3.7?0.8) mmol/L](P0.05).The incidence of fetal distress in the GIGT group(9.8%)was lower than that in DM group(20.2%)and GDM group(21.4%,P