Aim To investigate the effects of 1 7-me-thoxyl-7-hydroxyl-benzofuran chalcone(YLSC)on my-ocardial ischemia /reperfusion injury(MI /RI)by mod-ulating PI3K/Akt signaling pathway and the possible mechanisms.Methods Male SD rats were randomly
divided into sham group,model group,YLSC group, wortmannin(WM)group and YLSC +WM group(n =8).The rat model of MI /RI was established by ligation of the left anterior descending artery for 30 min fol-lowed by loosening the ligature for 2 h.After reperfu-
sion,blood samples were obtained to determine serum contents of CK-MB,LDH,NO and TNF-α.The pro-tein levels of total (t)-Akt,phosphorylated (p)-Akt and LC3-Ⅱ were detected by Western blot.Caspase-3,Beclin1 and eNOS mRNA expression was evaluated by FQ-PCR.Results YLSC pretreatment greatly re-duced serum levels of CK-MB,LDH and TNF-α,and elevated NO content.It also inhibited the expression of
caspase-3,Beclin1 and LC3-Ⅱ,while enhanced p-Akt and eNOS expression.Conclusion YLSC protects the heart against MI /RI via inhibition of apoptosis and excessive autophagy,in which protective effect is regu-lated by activation of the PI3K/Akt pathway.

Objective To investigate the plasma vitamin D3 level and its association with B cell subsets of patients with primary Sj(o)gren's syndrome (pSS).The role of vitamin D3 levels in the pathogenesis of pSS was explored.Methods The expression of plasma vitamin D3 levels of 55 patients with pSS and 32 controls were analyzed by ELISA.Frequencies of peripheral blood CD19+CD27-na(i)ve B cells,CD19+CD27+ memory B cells and CD19+CD27high plasma cells were analyzed by flow cytometry in 34 pSS patients without therapy and 22 controls.The relationship between the vitamin D3 levels and B cell subsets,SSDAI,tear flow rate,saliva flow rate,rheumatoid factor,immunoglobulin was analyzed in pSS patients.Non-parametric test,t test,one-way ANOVA,x2test,Pearman's and Spearman's correlation analysis were used for statistical analysis.Results ① There was significant difference in the levels of plasma 1,25 (OH)2D3 between the pSS patients group and normal control group,1,25 (OH)2D3 was significantly lower in pSS patients than that in the normal control group [24.17(22.20,28.41) pg/ml and 41.25(23.38,62.18) pg/ml,P＜0.05],and that was also obviously lower in the active group [22.64(20.74,24.90) pg/ml] than that in the normal control group (P＜0.05),and that was also obviously lower in the active disease group than that in the inactive disease group [25.39 (23.16,33.09) pg/ml,P＜0.05],but there was no difference between the inactive group and the normal control group (P＞0.05).② The percentage of peripheral blood of CD19+CD27high plasma cells and CD19+CD27+ memory B cells in CD19+ cells was reduced in patients in the pSS group compared with the control group [(0.89±0.30)％ and (1.72±0.43)％,(24±8)％ and (34±5)％; P＜0.05],and that was also significantly lower in the active group [(1.03±0.59) ％ ; (26± 10)％] and inactive group [(1.00±0.16)％,(26± 3)％] than that in the normal controls (P＜0.05).However,there was no difference between the active group and the inactive group (P＞0.05),but the frequency of peripheral blood of CD19+ CD27-naive B cells in CD19+ B cells was increased in patients with pSS compared with normal control group [(75.4±7.5)％ and (63.9±5.2)％,P＜0.05],and that was also significantly higher in the active group [(73.4±9.7)％] and inactive group [(73.3±2.9)％] than that in the normal control (P＜0.05),there was no difference between the active group and the inactive group.③ Significant negative correlation was observed between 1,25 (OH)2D3 and the percentage of peripheral blood CD19+CD27+ memory B cells in CD19+ cells as well as immunoglobulin G(r=-0.627,P=0.039; r=-0.657,P＜0.01) level.Conclusions These results demonstrate that abnormality of vitamin D levels may play an important role in the pathogenesis of pSS.

To investigate the TGFβ1-induced epithelial-mesenchymal transition (EMT) of Huh7 hepatoma cells caused by interaction of hepatitis B spliced protein (HBSP) with transforming growth factor beta-1-induced transcript 1 protein (TGFβ31I1),coding region of HBSP was cloned into lentiviral expression vector.Huh7 hepatoma cells were infected by recombinant lentivirus packaged in 293T cells.Stable cell lines expressing HBSP or control cells were selected by puromycin.Cells were incubated with 5 ng/mL TGFβ1 for 24 h,and observed under contrast-phase microspcope.Then the whole cell lysates were collected for western blot analysis using specific antibodies against EMT markers including E-cadherin,N-cadherin,Claudin-1 and β-catenin.To evaluate the effects of HBSP-TGFβ1I1 interaction on EMT,TGFβ1-induced EMT marker transition,as well as cell invasion and migration were explored after knocking down of TGFβ1I1 by siRNA.Results showed that Huh7 cell lines expressing HBSP (Huh7-HBSP flag-HIV) and control cell lines (Huh7-flag-HIV) were successfully established.Huh7-HBSP flag-HIV cells lost their pebble-like shape and tight cell-cell adhesion and transformed into the mesenchymal-like cells in the presence of TGFβ1.Decreased expression level of epithelial marker of E-cadherin,Claudin-1,β-catenin,increased expression level of mesenchymal marker of N-cadherin,and enhanced migration and invasion abilities were observed in Huh7-HBSP-flag-HIV cells as compared to the control cells.Moreover,the changes of EMT markers and metastasis abilities of Huh7-HBSP-flag-HIV cells could be reversed when TGFβ111 was knocked down by siRNA.In conclusion,HBSP could promote hepatoma cell migration and invasion by triggering EMT via interaction with TGFβ111.Our findings highlight new insights for HBSP-induced HCC progression.

Objective To describe the distribution of mannose binding lectin (MBL) genetic polymorphisms in non-acquired immunodeficiency syndrome (AIDS) patients with cryptococcosis in China and to verify the association of MBL polymorphisms with susceptibility to cryptococcosis.Methods The case-controlled genetic association study was conducted and 167 non-AIDS patients with cryptococcosis and 208 healthy controls were recruited. Genome DNA was extracted from the peripheral blood and MBL gene was amplified by polymerase chain reaction (PCR). Six singlenucleotide polymorphisms ( SNP) of MBL gene were sequenced. The association of MBL polymorphisms with susceptibility to cryptococcosis were analyzed. The comparison between patients and controls was performed by chi square test or Fisher's exact test. The differences of MBL plasma concentrations between groups with different MBL genotypes were compared by single factor variance analysis. Results There were no differences between patients and controls in terms of MBL genotype frequencies, haplotypes and genotypes (all P>0. 05). Compared with healthy control, the deficient MBL-producing genotypes were strongly associated with cryptococcal meningitis (16. 5% vs 8. 7%,χ2=4.25, P=0.0392, OR = 2.09), particularly in patients without underlying immunocompromised conditions (21. 4% vs 8. 7%, χ2 =7. 15, P = 0. 0075, OR = 2. 88). Individuals with MBL deficiency genotypes showed significantly higher rates of central nervous system (CNS) cryptococcal infection rather than non-CNS cryptococcosis (16. 5% vs 3. 1%, Fisher's exact test, P = 0. 010, OR = 6. 13).The difference was even more significant in the immunocompetent patients (21. 4% vs 4. 0%, P =0.009, OR= 6. 55). Conclusion MBL deficiency is associated with cryptococcal meningitis and may play a role in CNS Cryptococcus infection.

OBJECTIVE To investigate the characteristics and regulations of medication in different stages of disease by constructing a dynamic disease network and a cellular feature network spanning from myocardial infarction to heart failure.METHODS Based on transcrip-tome and single-cell sequencing data from a mouse model of left anterior descending coro-nary artery ligation,a dynamic early-middle-late network and cellular feature network were con-structed by integrating differential gene expres-sion trends and biological functions.The robust-ness of the perturbation effect of traditional Chi-nese medicine(TCM)on the disease network was calculated based on multi-target TCM,and we acquired the foundational data by analyzing the results of effectiveness.The predictive plat-form was scrutinized and assessed with regards to the functional attributes of FDA approved-drugs and compound prescriptions,in order to determine the primary stages of intervention and the drug patterns actions in the progression of heart failure.RESULTS In this study,we devel-oped a prediction and analysis platform for assessing the efficacy of drugs using a network-based approach.The accuracy of the system was validated by FDA approved-drugs.It was found that blood-activating drugs,heat-clearing drugs,and phlegm-expelling drugs exhibited favorable intervention effects during the early to middle stages of the disease by investigating the effects of single herbs and TCM prescriptions on disease progression.Similarly,phlegm-expelling drugs,spirit-nourishing drugs,and diuretic showed better intervention effects during the mid-dle to late stages.These findings were consis-tent with the clinical use of drugs.Analysis of the clustering heatmap results of TCM prescriptions revealed that the formulas aimed at qi stagnation and blood stasis had a strong effect in early stage,while the formulas for qi and yin deficiency and cardiorenal yang deficiency had a strong effect in the middle to late stages.Furthermore,analysis of the single-cell feature network demon-strated that TCM had advantages in modulating the changes in fibroblasts,myofibroblasts,endo-thelial cells,and granulocytes during the patho-logical process.Additionally,most prescriptions exhibited strong perturbation effects on the fea-ture network of NK-T cells,granulocytes,macro-phages,and myofibroblasts.CONCLUSION This platform quantitatively evaluates the primary action stages and characteristics of TCM and for-mulas involved in the dynamic process of myo-cardial infarction to heart failure based on the effective prediction of the efficacy of TCM and FDA approved-drugs.It provides reference for the precise clinical application of TCM and formu-las with multiple targets and multiple pathways.

A great number of studies have demonstrated functional abnormalities in children with attention-deficit/hyperactivity disorder (ADHD), although conflicting results have also been reported. And few studies analyzed homotopic functional connectivity between hemispheres. In this study, resting-state functional magnetic resonance imaging (MRI) data were recorded from 45 medication-naïve ADHD children and 26 healthy controls. The regional homogeneity (ReHo), degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) values were compared between the two groups to depict the intrinsic brain activities. We found that ADHD children exhibited significantly lower ReHo and DC values in the right middle frontal gyrus and the two values correlated with each other; moreover, lower VMHC values were found in the bilateral occipital lobes of ADHD children, which was negatively related with anxiety scores of Conners' Parent Rating Scale (CPRS-R) and positively related with completed categories of Wisconsin Card Sorting Test (WCST). Our results might suggest that less spontaneous neuronal activities of the right middle frontal gyrus and the bilateral occipital lobes in ADHD children.