Background and purpose:Brucine is one of the active components from Strychnos nux vomica,with signifi cant analgesic,anti-inflammatory and platelet-aggregating inhibitory properties.Due to its cytotoxic effect,the anti-tumor effect of brucine has increasingly been appreciated.In this study,we investigated the impact of brucine on A549 cells proliferation,apoptosis as well as the underlying mechanisms.Methods:MTT assay was used to examine the cell viability,flow cytometric analysis and fluorescent microscope were applied to examine cell apoptosis,ELISA method was used to examine the effect of brucine on PGE2 release from A549 cells and RT-PCR analysis was used to measure mRNA content,western blotting analysis was used to measure protein expression and luciferase activity was detected to examine the effect of brucine on COX-2 promoter activity.Results:Brucine was able to suppress the proliferation of A549 cells and induce cell apoptosis to time-dependent and dose-dependent manner.To understand the mechanisms,COX-2 was identifi ed to be an important target molecule involved in the apoptosis induced by brucine because brucine could suppress the COX-2 mRNA,protein expressions as well as PGE2 release in A549 cells in a timedependent manner.Furthermore,overexpression of COX-2 abrogated brucine-induced cell apoptosis,in contrast,when A549 cells were transfected with COX-2 siRNA,the apoptotic effect of brucine was dramatically enhanced.Further analysis revealed that brucine was able to suppress COX-2 transcriptional activation.Conclusion:Brucine was able to induce lung cancer apoptosis via downregulation of COX-2.

Objective To study the expression and clinical significance of BRCA1 and BRCA2 in sporadic breast cancer in women of Jiaodong peninsula. Methods Immunohistochemistry and tissue array were used to detect the expression of BRCA1 and BRCA2 in 100 cases of sporadic breast cancer and 30 cases of benign breast tumor in women of Jiaodong peninsula. Results ① The expression rate of BRCA1 and BRCA2 was 49% (49/100) and 50% (50/100) in breast cancer, 80% (24/30) and 83.33% (25/30) in benign breast lesions respectively. The expression rate of BRCA1 and BRCA2 in breast cancer was lower than that in benign breast lesions (P<0.05). ② The expression of BRCA1 and BRCA2 was uncorrelated with factors such as tumor size, lymphatic metastases, age and menopause or not(P>0.05). ③ There was no dependency between the expression of BRCA1 and BRCA2 (P> 0. 05). Conclusions The expression rate of BRCA1 and BRCA2 in breast carcinoma in women of Jiaodong peninsula was lower than that in benign breast lesions, suggesting that the expression of BRCA1 and BRCA2 was related to the occurrence of sporadic breast carcinoma in women of Jiaodong peninsula. However, the role of BRCA1 and BRCA2 in the genesis and development of the breast carcinoma is independent.

OBJECTIVETo study the molecular mechanism of cyclooxygenase-2 (COX-2), one of effective ingredient of brucine, in inducing non-small cell lung cancer cell apoptosis.

METHODCOX-2 promoter, transcription factor deletion mutants and COX-2 mRNA 3'-UTR-containing report plasmids were transfected with Renillia to non-small cell lung cancer A549 cell, in order to detect the activity of report gene luciferase and minimum cis-acting element of COX-2 promoter inhibited by brucine. The influence of brucine on IkappaB phosphorylation and the nuclear translocation of p65 were detected by immunoblotting assay.

RESULTBrucine significantly suppressed LPS-induced COX-2 promoter activation, but revealed minor impact on COX-2 mRNA stability. NF-kappaB in the vicinity of COX-2 promoter-262 was an important cis-acting element of brucine for inhibiting the activity of COX-2 promoter. Brucine was found to inhibit the phosphorylation of IkappaBalpha as well as the nuclear translocation of p65.

CONCLUSIONBrucine can improve A549 cells apoptosis by inhibiting the activity of NF-kappaB and the subsequent COX-2 gene expression.

Biological Transport ; drug effects ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; Cell Line, Tumor ; Cyclooxygenase 2 ; genetics ; Humans ; NF-kappa B ; metabolism ; Phosphorylation ; drug effects ; Promoter Regions, Genetic ; drug effects ; genetics ; RNA Stability ; drug effects ; Strychnine ; analogs & derivatives ; pharmacology

Objective:To explore the role of hippocampal γ oscillation abnormality in sepsis-associated encephalopathy (SAE).Methods:Seventy male Sprague-Dawley rats (2-3 months) were randomly (random number) divided into three groups according to the random digital table method: sham, CLP, and CLP + dopamine 4 (D4) receptor agonists RO-10-5824 group. The SAE animal model was established by cecal ligation and puncture (CLP). On day 10-14 after surgery, the open field, novel object recognition, and fear conditioning tests were performed. After that, the hippocampus was collected to measure expressions of parvalbumin (PV) and D4 receptor. In another set of experiment, CA1 local field potential (LFP) were recorded, and the relationship between LFP and time with novel object was analyzed. Independent sample t-test was used for pairwise comparisons, and multiple comparisons were performed by one-way ANOVA, followed by the Tukey multiple comparisons test. Correlation was analyzed using Pearson correlation. Statistical significance was assumed when P<0.05. Results:Compared with the sham group, hippocampal PV (77.54±4.61)%, D4 expression (56.36±3.88)% and γ oscillation power (41.1±8.62)%, object exposure time (36±3) s, new object recognition rate (49±4)%, and scene stiffness time (56±7) s were decreased significantly ( P<0.05). However, RO-10-5824 treatment could increase hippocaml γ oscillation power (92.3±6.7)%, and reverse the decreased new object exposure time (44±3) s and new object recognition rate (63±4)%. Correlation analysis showed that hippocampal γ oscillation power was positively associated with new object exposure time ( r=0.609 2, P=0.015 9). There was no difference in total distance traveled or time spent in the center among groups ( P>0.05). Conclusion:Hippocampal γ oscillation abnormality might play a key role in cognitive impairment associated with SAE.

We wished to undertake molecular genetic typing and evaluate recombinants of the hepatitis-B virus (HBV) in Tibet (China). Multistage random sampling was used to collect HBsAg-positive samples. Nested polymerase chain reactions were used to amplify the whole sequence of the HBV. DNAstar, MEGA6 and SimPlot were used to assemble sequences, create phylogenetic trees, and undertake recombination analyses. Twelve whole sequences of the HBV of a Tibetan population were collected using these methods. Results showed that all 12 strains were C/D recombinants. Nine of the recombinations were at nt750, and the other three at nt1526. Therefore, the 12 strains could be divided into two types of recombinants: C/Da and C/Db. Analyses of the sequence of the whole genome revealed that the 12 strains belonged to genotype C, and that the nucleotide distance was > 4% between the 12 strains and sub-genotypes C1 to C15 in Genbank. The most likely sub-genotype was C1. Individuals with C/Da were from central and northern Tibet (e.g., Lasa, Linzhi, Ali) and those with C/Db recombinants were from Shannan in southern Tibet. These data suggest that the two types of recombinants had a good distribution in Tibet. Also, they can provide important information for studies on HBV recombination, gene features, virus evolution, as well as the control and prevention of HBV infection in Tibet.
Adult ; Female ; Genotype ; Hepatitis B ; virology ; Hepatitis B virus ; classification ; genetics ; isolation & purification ; Humans ; Male ; Phylogeny ; Recombination, Genetic ; Sequence Analysis, DNA ; Tibet ; Young Adult

Objective Our preliminary study demonstrates that quercetin can inhibit the proliferation of HL-60 cells. This sudy aimed to find some drugs which could have synergistic effects with quercetin on apoptosis of HL-60 cells. Methods HL-60 cells were cultured with bortezomib at different concentrations (1, 2, 4, 8, 16, and 32μmol/L) alone or combined with quercetin at different concentrations for 48 h. HL-60 cells were cultured with lenalidomide at different concentrations (5, 10, 20, 40, 80, 160, and 320 μmol/L) alone or in combination with quercetin at different concentrations for 48 h. The CCK-8 assay was used to determine the effects on proliferation of HL-60 cells. Results Bortezomib significantly inhibited the proliferation of HL-60 cells (P<0.01). IC50 of quercetin was 49.24μmol/L after cells treated by quercetin combined with bortezomib, which was 13.44μmol/L lower than that treated by quercetin alone. Isobolographic analysis revealed the two drugs had synergistic effect. The results of cell viability of HL-60 cells treated by lenalidomide at lower concentrations (5, 10, 20, 40, and 80μmol/L)were not different from those of the control group (P > 0.05). The results of cell viability of HL-60 cells treated by lenalidomide at higher concentrations (160 and 320μmol/L) were lower than those of the control group (P<0.05). IC50 of quercetin after cells treated by quercetin combined with bortezomib was not different from that treated by quercetin alone. Isobolographic analysis revealed the two drugs had no synergistic effect. Conclusions Bortezomib can inhibit the proliferation of HL-60 cells and it has a synergistic effect with quercetin on HL-60 cells. Lenalidomide has a weaker role in inhibition of the proliferation of HL-60 cells, and it has no synergistic effect with quercetin on HL-60 cells.

Objective: To analyze the changing epidemiological characteristics of hepatitis E cases in China, in order to promote in preventing and controlling hepatitis E. Methods: Data of hepatitis E and outbreaks reported through national notifiable diseases reporting system were analyzed from 2004 to 2017, but data of Hongkong, Macau and Taiwan were not included. Data of hepatitis E were divided into three phases as 2004-2007, 2008-2011 and 2012-2017, representing eight years before, four years before and years after the postmarketing of hepatitis E vaccine. Linear regression was used for analyzing the trend of hepatitis E, improved muster method was used for analyzing the seasonal intensity. Results: From 2004 to 2017, 329 519 hepatitis E cases were reported and the annual incidence were increasing from 1.27/100 000 to 2.10/100 000 (t=6.87, P<0.001). The concentrations of hepatitis E during 2004-2007, 2008-2011 and 2012-2017 were 17.43, 16.06, 11.17, respectively, with low seasonal intensity. Number of cases reported by Jiangsu, Guangdong and Zhejiang accounted for 31.54% of national cases. The incidence were lower in central (1.45/100 000) and western (1.11/100 000) region than that in eastern region (2.67/100 000), but were increasing continuously. There was an increasing trend of incidence with growing ages (t=7.85, P<0.001). The incidence was higher than 2/100 000 among cases aged ≥40, and was the highest (5.22/100 000) in the age group of 65-69 years old. Farmers, retired persons, houseworkers and unemployees accounted for 67.46% of total cases. A total of 7 outbreaks were reported, among which 3 were in nursing homes. Conclusion The incidence of hepatitis E in central and western regions were increasing continuously and the surveillance should be strengthened. There was higher risk among middle-aged population, farmers and nursing homes, so strategy for immunization among those population was in great need.

Objective: To analyze the epidemiological characteristics of hepatitis A cases in China from 2004 to 2015. Methods: Data of hepatitis A were reported through national notifiable disease information reporting system, which covered the 31 provinces (Hong Kong, Macau and Taiwan excluded). The inclusion criteria was: date of illness onset was between January 1^st 2004 and December 31^st 2015, the status of reported card was confirmed, the case was classified as laboratory confirmed or clinical diagnosed, the disease was Hepatitis A. The information such as sex, date of birth, date of illness onset, place of residence was collected. The data was divided into three phases, 2004-2007, 2008-2011, 2012-2015, which represented the phase before expanded program on immunization (EPI), first 4 years after EPI, second 4 years after EPI. Results: From 2004 to 2015, there were totally 574 697 hepatitis A cases in China, the mean annual incidence was 3.62/100 000. The risk ratio of hepatitis A in 2015 was 0.23 when compared with 2004. Sichuan, Xinjiang and Yunnan contributed to 27.27% of the total cases in China. In 2012-2015, the incidence of western (3.46/100 000) region was significantly higher than that in central (1.21/100 000) and eastern (1.08/100 000) regions. From 2004-2015, number of cases in each age group declined greatly, with number of cases declining from 43 711 to 5 938 in the age group of 5-9 years, from 29 722 to 3 438 in 10-14, from 23 212 to 3 646 in 15-19. The number of cases declined from 24 079 to 10 304 in the age group of 0-4 (declined by 57.21%), but in 2012-2015, the incidence of 0-4 age group was still the highest, with 77.72% cases in Xinjiang and Sichuan. Famers, students and scattered children accounted for 69.95% of total cases, with student cases declined from 24.08% (2004-2007) to 8.67% (2012-2015). Conclusion The incidence of hepatitis A in China is decreasing year by year, the risk has been decreasing to a relatively low level. However, in western regions and children under age five, the risk is still high. Precision intervention is needed for further prevention and control of hepatitis A.

Objective:To understand the epidemiological characteristics of hepatitis B in China, evaluate the performance of elimination hepatitis B in China and provide scientific evidence for the prevention and control of hepatitis B.Methods:An analysis was conducted by using the data of hepatitis B cases reported to the National Notifiable Disease Reporting System (NNDRS) from the areas with low, moderate and high hepatitis B prevalence in China from 2013 to 2020, and the information about the diagnoses of the hepatitis B cases were collected, the incidence of hepatitis B was estimated according to the reporting and diagnosis information and the characteristics of acute and chronic hepatitis B were compared.Results:A total of 27 013 hepatitis B cases were reported to NNDRS, including 4 070 acute cases, 21 971 chronic cases and 972 unclassified cases. Among the reported acute hepatitis B cases, 69.9% (2 845/4 070) were confirmed. Among the reported chronic hepatitis B cases, 89.0% (19 548/21 971) were confirmed, and 2.1% (452/21 971) were confirmed as acute cases. It was estimated that the incidence of acute hepatitis B was 4.6/100 000 and the incidence of chronic hepatitis B cases was 54.5/100 000. The case number of acute hepatitis B in age group 31-45 years was highest, accounting for 35.3% (1 164/3 297). The case number of acute hepatitis B in children under 15 years old was lowest, accounting for 0.4% (13/3 297). The case number of chronic hepatitis B in age group 46-60 years was highest, accounting for 34.4% (7 211/20 932).Conclusions:The incidence of acute hepatitis B was in decrease and the incidence of chronic of hepatitis B was in increase in China year by year. It is important to strengthen the standardized diagnosis and treatment of chronic hepatitis B to decrease the morbidity and mortality of hepatitis B. At the same time, it is necessary to standardize the management and reporting of hepatitis B cases reported to NNDRS to improve the accuracy of the reporting of hepatitis B.