As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective:To study the role of special microbial communities in the development of periodontitis in type 2 diabetes melli-tus(T2DM)patients.Methods:40 subjects aged 20-70 years were included and divided into 3 groups:moderate to severe periodon-titis with T2DM(SP.T2DM,n=15),moderate to severe periodontitis group(SP,n=15)and normal healthy group(N,n=10).The basic information,periodontal clinical indicators and blood sugar of the subjects were recorded.Subgingival plaque samples were col-lected,DNA samples of the plaque were extracted,and sequenced by Illumina NovaSeq6000 platform.The microbial diversity,eco-logical characteristics and functions of the plaque were analyzed by Uparse,SPSS and other softwares.Results:481 species in 22 phyla,30 classes,73 orders,129 families and 265 genera were obtained from the samples.Beta polymorphism analysis showed that the species composition of CP.T2DM group and CP group was similar.Alpha polymorphism analysis showed that the species richness and evenness in CP.T2DM group and CP group were higher than those in N group(P＜0.01).Venn diagram analysis showed that the species richness of the plaque in CP.T2DM group was the highest,followed by CP group and the lowest in N group.At the genus lev-el,Klebsiella and Bifidobacterium in CP.T2DM group were larger than those in CP group and N group(P＜0.05),and between group CP and N,P＞0.05.At the species level,the Capnocytophaga leadbetteri in CP.T2DM group was higher than that in CP group and N group(P＜0.05),between group CP and N,P＞0.05;There were some differences in the microbial community structure of subgingival plaque among the 3 groups.The species richness of subgingival flora in patients with CP and T2DM was higher than that in patients with CP and healthy people.Conclusion:The increase of Klebsiella,Bifidobacterium and Capnocytophaga leadbetter in subgingival flora of patients with moderate and severe periodontitis may be related to the development of T2DM.

Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.
Humans ; Mitophagy ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Cell Line ; Autophagy ; Apoptosis ; Membrane Proteins ; Proto-Oncogene Proteins/genetics* ; Tumor Suppressor Proteins/pharmacology*

Cordyceps sinensis(C.sinensis)is a widely used and highly valuable traditional Chinese medicine.Several dipeptides have been detected in C.sinensis,but current scientific knowledge of its chemical makeup remains limited.In this study,an improved approach that integrates offline two-dimensional liquid chromatography(2D LC)separation,precursor ion list,library screening,and diagnostic ion filtering was established to systematically screen and characterize dipeptides in C.sinensis.Offline 2D LC integrating hydrophilic interaction LC and reverse phase separations was established to eliminate interference and identify the target dipeptides.A library containing the potential 400 dipeptides was created,and a precursor ion list with all theoretical precursor ions was adopted to trigger the MS/MS scan with high sensitivity.To identify dipeptides,the type and connection sequence of amino acids were determined according to the product ions.Ile and Leu residues were differentiated for the first time according to the characteristic ion at m/z 69.07.Ultimately,170 dipeptides were identified or tentatively characterized from C.sinensis,and most are reported for the first time in this species herein.In addition,the identified dipeptides were also applied for discrimination among the three Cordyceps species,and 11 markers were identified.The obtained results provide a deeper understanding of the chemical basis of C.sinensis.

BACKGROUND: Chronic noise exposure is one environmental hazard that is associated with genetic susceptibility factors that increase Alzheimer's disease (AD) pathogenesis. However, the comprehensive understanding of the link between chronic noise stress and AD is limited. Herein, we investigated the effects of chronic noise exposure on AD-like changes in senescence-accelerated mouse prone 8 (SAMP8). METHODS: A total of 30 male SAMP8 mice were randomly divided into the noise-exposed group, the control group, and aging group (positive controls), and mice in the exposure group were exposed to 98 dB SPL white noise for 30 consecutive days. Transcriptome analysis and AD-like neuropathology of hippocampus were examined by RNA sequencing and immunoblotting. Enzyme-linked immunosorbent assay and real-time PCR were used to further determine the differential gene expression and explore the underlying mechanisms of chronic noise exposure in relation to AD at the genome level. RESULTS: Chronic noise exposure led to amyloid beta accumulation and increased the hyperphosphorylation of tau at the Ser202 and Ser404 sites in young SAMP8 mice; similar observations were noted in aging SAMP8 mice. We identified 21 protein-coding transcripts that were differentially expressed: 6 were downregulated and 15 were upregulated after chronic noise exposure; 8 genes were related to AD. qPCR results indicated that the expression of Arc, Egr1, Egr2, Fos, Nauk1, and Per2 were significantly high in the noise exposure group. These outcomes mirrored the results of the RNA sequencing data. CONCLUSIONS These findings further revealed that chronic noise exposure exacerbated aging-like impairment in the hippocampus of the SAMP8 mice and that the protein-coding transcripts discovered in the study may be key candidate regulators involved in environment-gene interactions.

The occurrence of endoplasmic reticulum stress (ERS) is involved in the development of various diseases in human body.Accurate and effective intervention and regulation of ERS has become a hot spot in recent years.Amino acids are the nutrients that make up the proteins that people need, and they are also important signal transduction molecules in the human body.Intervention and regulation of ERS stress by amino acids is likely to be an important and unexplored area, and it is expected to become a potential target for new prevention strategies such as malignant tumors and cardiovascular diseases.Therefore, in this article, we will briefly review the research progress of the effects of amino acids on cellular ERS stress in recent years.

Objective: To discuss the rationality of stage pT3 in the AJCC 8^th TNM criteria of gallbladder carcinoma. Methods: A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage: tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure; (2) pT3b stage: tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females, aged 36 to 80 years, with a median age of 59 years; 43 patients with pT3b, including 24 males and 19 females, aged 41 to 78 years old, median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t-test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non-normally distributed measurement data.The comparison of the count data was performed by χ² test or Fisher exact probability method. Survival analysis was performed using Kaplan-Meier method, and survival rate was compared using Log-rank test. Results: (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19-9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816, -1.966, -3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days) (P<0.05). (2) The 1-, 3-, 5-year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ²=5.117, P=0.024). (3)The 1-, 3-year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ²=4.976, P=0.026). Conclusions pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8^th gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient′s basic condition and surgical tolerance.

Objective To discuss the rationality of stage pT3 in the AJCC 8th TNM criteria of gallbladder carcinoma. Methods A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage:tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure;(2) pT3b stage:tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females,aged 36 to 80 years,with a median age of 59 years;43 patients with pT3b, including 24 males and 19 females,aged 41 to 78 years old,median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t?test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non?normally distributed measurement data.The comparison of the count data was performed by χ2 test or Fisher exact probability method. Survival analysis was performed using Kaplan?Meier method, and survival rate was compared using Log?rank test.Results (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19?9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816,-1.966,-3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days)(P<0.05).(2) The 1?,3?, 5?year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ2=5.117, P=0.024). (3)The 1?, 3?year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ2=4.976, P=0.026). Conclusions pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8th gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient′s basic condition and surgical tolerance.

Objective To discuss the rationality of stage pT3 in the AJCC 8th TNM criteria of gallbladder carcinoma. Methods A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage:tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure;(2) pT3b stage:tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females,aged 36 to 80 years,with a median age of 59 years;43 patients with pT3b, including 24 males and 19 females,aged 41 to 78 years old,median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t?test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non?normally distributed measurement data.The comparison of the count data was performed by χ2 test or Fisher exact probability method. Survival analysis was performed using Kaplan?Meier method, and survival rate was compared using Log?rank test.Results (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19?9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816,-1.966,-3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days)(P<0.05).(2) The 1?,3?, 5?year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ2=5.117, P=0.024). (3)The 1?, 3?year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ2=4.976, P=0.026). Conclusions pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8th gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient′s basic condition and surgical tolerance.

Objective: Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination. Methods: According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 μg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T₀), four years (T₁) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively. Results: Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T₀ and it decreased to 16.51% (149/529) at T₁. The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T₀ to T₁. Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T₀ were significantly higher at T₁. The positive rate at T₁ among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T₀ were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95%CI) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T₁ among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T₀ were higher than those whose anti-HBs titer<200 mU/ml. The b value (95% CI) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T₁. The b value (95% CI) of GMC was 0.86 (0.04-1.68). Conclusion Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.