1.Celastrol-loaded ginsenoside Rg3 liposomes boost immunotherapy by remodeling obesity-related immunosuppressive tumor microenvironment in melanoma.
Hongyan ZHANG ; Jingyi HUANG ; Yujie LI ; Wanyu JIN ; Jiale WEI ; Ninghui MA ; Limei SHEN ; Mancang GU ; Chaofeng MU ; Donghang XU ; Yang XIONG
Acta Pharmaceutica Sinica B 2025;15(5):2687-2702
Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8+ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8+ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.
2.Seroepidemiological analysis of hepatitis B virus infection among adolescents aged 0-14 years in Henan Province and preliminary evaluation of the effectiveness of childhood hepatitis B vaccine immunization program
Yonghao GUO ; Yanping CHEN ; Qiaohua DOU ; Qian LIU ; Jianhui YANG ; Minghua SENG ; Wanyu LYU ; Changshuang WANG ; Mingxia LU ; Jin XU ; Yanyang ZHANG ; Dongyang ZHAO
Chinese Journal of Preventive Medicine 2024;58(2):202-207
Objective:To analyze the seroepidemiological characteristics of hepatitis B virus (HBV) infection among adolescents aged 0-14 years in Henan Province and to evaluate the effectiveness of the childhood hepatitis B vaccine (HepB) immunization program.Methods:From September 2021 to March 2022, a total of 4 883 adolescents aged 0-14 years were selected from 25 villages or communities of 18 provincial-level cities in Henan Province by using the multi-stage random cluster sampling method. Demographic data were collected through questionnaires. The 3 ml of blood samples were collected from individuals aged 0-4 years and 5 ml of blood samples were collected from individuals aged 5-14 years to test HBsAg, HBcAb and HBsAb. Data on vaccination were collected through Henan Provincial Immunization Information System and hepatitis B cases in Henan Province were collected through China Infectious Disease Reporting System. The effectiveness of the childhood HepB immunization program was analyzed.Results:The average age of 4 883 subjects was (7.32±2.81) years old. The positive rates of HBsAg and HBcAb were 0.1% (7/4 883) and 1.0% (50/4 883), and the population standardized rates were 0.3% and 1.7%. In 2002, the positive rate of HBsAg among adolescents aged 0-14 years in Henan Province was 3.39%. Compared with that in 2002, the number of chronic HBV infections among adolescents in Henan Province in 2022 decreased by about 0.7 million. In 2002, the vaccination rate of newborns who completed all three doses of vaccine was 6.26%. In 2003, the vaccination rate of the hepatitis B vaccine rose rapidly, reaching 90% in 2013 for the first time. After 2014, the vaccination rate in Henan Province continued to remain above 95%. The proportion of cases among children aged 1-4 years in clinical reports decreased from 0.43% (1 108/256 566) in 2006 to 0.01% (78/80 655) in 2021. The proportion of cases among adolescents aged 5-19 years decreased from 18.21% (46 710/256 566) in 2006 to 1.1% (827/80 655) in 2021.Conclusions:From 2002 to 2022, the positive rate of HBsAg among adolescents aged 0-14 years has decreased significantly in Henan Province. The effectiveness of the HepB immunization program for children is good.
3.Seroepidemiological analysis of hepatitis B virus infection among adolescents aged 0-14 years in Henan Province and preliminary evaluation of the effectiveness of childhood hepatitis B vaccine immunization program
Yonghao GUO ; Yanping CHEN ; Qiaohua DOU ; Qian LIU ; Jianhui YANG ; Minghua SENG ; Wanyu LYU ; Changshuang WANG ; Mingxia LU ; Jin XU ; Yanyang ZHANG ; Dongyang ZHAO
Chinese Journal of Preventive Medicine 2024;58(2):202-207
Objective:To analyze the seroepidemiological characteristics of hepatitis B virus (HBV) infection among adolescents aged 0-14 years in Henan Province and to evaluate the effectiveness of the childhood hepatitis B vaccine (HepB) immunization program.Methods:From September 2021 to March 2022, a total of 4 883 adolescents aged 0-14 years were selected from 25 villages or communities of 18 provincial-level cities in Henan Province by using the multi-stage random cluster sampling method. Demographic data were collected through questionnaires. The 3 ml of blood samples were collected from individuals aged 0-4 years and 5 ml of blood samples were collected from individuals aged 5-14 years to test HBsAg, HBcAb and HBsAb. Data on vaccination were collected through Henan Provincial Immunization Information System and hepatitis B cases in Henan Province were collected through China Infectious Disease Reporting System. The effectiveness of the childhood HepB immunization program was analyzed.Results:The average age of 4 883 subjects was (7.32±2.81) years old. The positive rates of HBsAg and HBcAb were 0.1% (7/4 883) and 1.0% (50/4 883), and the population standardized rates were 0.3% and 1.7%. In 2002, the positive rate of HBsAg among adolescents aged 0-14 years in Henan Province was 3.39%. Compared with that in 2002, the number of chronic HBV infections among adolescents in Henan Province in 2022 decreased by about 0.7 million. In 2002, the vaccination rate of newborns who completed all three doses of vaccine was 6.26%. In 2003, the vaccination rate of the hepatitis B vaccine rose rapidly, reaching 90% in 2013 for the first time. After 2014, the vaccination rate in Henan Province continued to remain above 95%. The proportion of cases among children aged 1-4 years in clinical reports decreased from 0.43% (1 108/256 566) in 2006 to 0.01% (78/80 655) in 2021. The proportion of cases among adolescents aged 5-19 years decreased from 18.21% (46 710/256 566) in 2006 to 1.1% (827/80 655) in 2021.Conclusions:From 2002 to 2022, the positive rate of HBsAg among adolescents aged 0-14 years has decreased significantly in Henan Province. The effectiveness of the HepB immunization program for children is good.
4.Research status and challenges in the prognosis of primary biliary cholangitis after liver transplantation
Lin CHEN ; Ning LIU ; Jinglan JIN ; Yanjun CAI ; Fang XU ; Junqi NIU ; Wanyu LI
Journal of Clinical Hepatology 2021;37(4):955-958
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with unknown etiology, and patients with poor response to ursodeoxycholic acid and obeticholic acid may eventually progress to liver cirrhosis and even liver failure. Liver transplantation is the only effective treatment method for PBC at present. This article elaborates on liver transplantation, survival time after liver transplantation, complications, recurrence of PBC after liver transplantation, and prospects and challenges of liver transplantation in patients with PBC, so as to provide a reference for clinical outcome and treatment after liver transplantation for PBC.
5. Analysis on the hemagglutinin genetic characteristic of 7 measles virus isolated in Henan Province in 2017
Daxing FENG ; Lu ZHANG ; Wanyu LYU ; Jianhui YANG ; Guangwei LI ; Jin XU ; Yanyang ZHANG
Chinese Journal of Preventive Medicine 2019;53(9):929-933
Objective:
Analyze the genetic characteristic of Hemagglutinin(H) gene of measles viruses isolated in Henan Province in 2017.
Methods:
Swab samples collected from 7 lab confirmed measles cases, and we got the measles virus by Vero/Slam inoculation. Fragment of H genes were amplified by reverse transcription polymerase chain reaction(RT-PCR), then the PCR products were sequenced and analyzed.
Results:
The age of the 7 measles confirmed cases were between 1 and 50 years old, and all of them were males. All the 7 measles viruses were identified as H1a genotype, and the average distance of the nucleotides and the amino acids was 0.005, respectively. Compared with the Shanghai-191/China-vaccine, there were some changes in isolated virus, such as 240th, 397th and 381st sites in the amino acid sequence.
Conclusion
The measles genotype which isolated in Henan Province in 2017 was H1a. There were some difference from Shanghai-191/China-vaccine in the nucleotides sequence of H gene, which suggested that it′s necessary to strengthen the monitor the variation of measles virus.
6.Genetic characteristics of mumps virus isolated from one outbreak in Henan province in 2016
Daxing FENG ; Lu ZHANG ; Wanyu LYU ; Guangwei LI ; Jin XU ; Yanyang ZHANG
Chinese Journal of Microbiology and Immunology 2019;39(3):221-227
Objective To analyze the genetic characteristics of mumps virus ( MuV) isolated from an outbreak in Henan province in 2016 and to provide reference data for the control of mumps in Henan prov-ince. Methods Swab specimens were collected from a mumps outbreak in Henan province in 2016. One virus strain was selected for whole genome sequencing after virus isolation and genotyping. MEGA7. 0 soft-ware was used to construct phylogenetic tree, to calculate P-distance and to analyze the characteristics of genes encoding small hydrophobic protein ( SH ) , fusion protein ( F ) and hemagglutinin neuraminidase ( HN) . Results Five swab specimens were collected in the outbreak and five MuV strains were successfully obtained. Phylogenetic analysis showed that all of them belonged to genotype F with a P-distance of 0. 047 (0. 046-0. 049 ) with the reference strain. The P-distance among the five MuV strains was 0. 001 ( 0-0. 003). Results of the whole genome sequencing of one MuV strain showed that the P-distance with the ref-erence virus was 0. 053 (0. 018-0. 072) and the smallest P-distance with genotype F was 0. 018. Compared with the vaccine strain (HQ416907. 1), the amino acid at 28-30 site of SH protein was IML. The 91, 195 and 383 amino acid sites in F protein were related to the pathogenicity of MuV, but no mutations were found in these sites. Some mutations were found in HN protein, such as P354Q, E356D and K464N, which were associated with the immunological characteristics of MuV. Conclusions MuV strains isolated from the out-break in Henan province in 2016 belonged to genotype F. The genetic characteristics of these MuV strains were similar to those prevalent in other provinces of China.
7.Analysis on the hemagglutinin genetic characteristic of 7 measles virus isolated in Henan Province in 2017
Daxing FENG ; Lu ZHANG ; Wanyu LYU ; Jianhui YANG ; Guangwei LI ; Jin XU ; Yanyang ZHANG
Chinese Journal of Preventive Medicine 2019;53(9):929-933
Objective Analyze the genetic characteristic of Hemagglutinin(H) gene of measles viruses isolated in Henan Province in 2017. Methods Swab samples collected from 7 lab confirmed measles cases,and we got the measles virus by Vero/Slam inoculation. Fragment of H genes were amplified by reverse transcription polymerase chain reaction(RT?PCR), then the PCR products were sequenced and analyzed. Results The age of the 7 measles confirmed cases were between 1 and 50 years old,and all of them were males. All the 7 measles viruses were identified as H1a genotype,and the average distance of the nucleotides and the amino acids was 0.005, respectively. Compared with the Shanghai?191/China?vaccine, there were some changes in isolated virus,such as 240th, 397th and 381st sites in the amino acid sequence. Conclusion The measles genotype which isolated in Henan Province in 2017 was H1a. There were some difference from Shanghai?191/China?vaccine in the nucleotides sequence of H gene,which suggested that it's necessary to strengthen the monitor the variation of measles virus.
8.Analysis on the hemagglutinin genetic characteristic of 7 measles virus isolated in Henan Province in 2017
Daxing FENG ; Lu ZHANG ; Wanyu LYU ; Jianhui YANG ; Guangwei LI ; Jin XU ; Yanyang ZHANG
Chinese Journal of Preventive Medicine 2019;53(9):929-933
Objective Analyze the genetic characteristic of Hemagglutinin(H) gene of measles viruses isolated in Henan Province in 2017. Methods Swab samples collected from 7 lab confirmed measles cases,and we got the measles virus by Vero/Slam inoculation. Fragment of H genes were amplified by reverse transcription polymerase chain reaction(RT?PCR), then the PCR products were sequenced and analyzed. Results The age of the 7 measles confirmed cases were between 1 and 50 years old,and all of them were males. All the 7 measles viruses were identified as H1a genotype,and the average distance of the nucleotides and the amino acids was 0.005, respectively. Compared with the Shanghai?191/China?vaccine, there were some changes in isolated virus,such as 240th, 397th and 381st sites in the amino acid sequence. Conclusion The measles genotype which isolated in Henan Province in 2017 was H1a. There were some difference from Shanghai?191/China?vaccine in the nucleotides sequence of H gene,which suggested that it's necessary to strengthen the monitor the variation of measles virus.
9.IL28B Is Associated with Outcomes of Chronic HBV Infection.
Xiaodong SHI ; Xiumei CHI ; Yu PAN ; Yanhang GAO ; Wanyu LI ; Chen YANG ; Jin ZHONG ; Damo XU ; Manna ZHANG ; Gerald MINUK ; Jing JIANG ; Junqi NIU
Yonsei Medical Journal 2015;56(3):625-633
PURPOSE: The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. MATERIALS AND METHODS: IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. RESULTS: Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001). CONCLUSION: Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.
Adult
;
Aged
;
Alanine Transaminase/blood
;
Asian Continental Ancestry Group/*genetics
;
Biological Markers/blood
;
Carcinoma, Hepatocellular/genetics
;
Case-Control Studies
;
China
;
DNA, Viral/blood
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Genotype
;
Hepatitis B virus/genetics
;
Hepatitis B, Chronic/ethnology/*genetics/immunology/*virology
;
Humans
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Interleukins/blood/*genetics/metabolism
;
Leukocytes, Mononuclear
;
Liver Cirrhosis/blood
;
Liver Neoplasms/genetics
;
Male
;
Middle Aged
;
RNA, Messenger/*genetics
;
Reverse Transcriptase Polymerase Chain Reaction

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