1.Targeting the chromatin structural changes of antitumor immunity
Li NIAN-NIAN ; Lun DENG-XING ; Gong NINGNING ; Meng GANG ; Du XIN-YING ; Wang HE ; Bao XIANGXIANG ; Li XIN-YANG ; Song JI-WU ; Hu KEWEI ; Li LALA ; Li SI-YING ; Liu WENBO ; Zhu WANPING ; Zhang YUNLONG ; Li JIKAI ; Yao TING ; Mou LEMING ; Han XIAOQING ; Hao FURONG ; Hu YONGCHENG ; Liu LIN ; Zhu HONGGUANG ; Wu YUYUN ; Liu BIN
Journal of Pharmaceutical Analysis 2024;14(4):460-482
Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.
2.Research on the health policy of early life:Based on analysis of policy texts of Beijing city
Xiao-Rui LIU ; Wei FU ; Ya-Lun WEI ; Ming-Xing WANG ; Chao-Fan XU ; Dian-Qi YUAN ; Chao GUO
Chinese Journal of Health Policy 2023;16(11):39-46
Objective:This paper mainly discusses the health policy of early life of pregnant women and infants in Beijing as an example,and to provide the basis for policy formulation and optimization.Methods:By using the content analysis method,149 policy texts are divided into two dimensions:policy objectives and policy instruments.The results are described by manual coding,cross analysis and trend analysis.Results:In regard to Policy Objectives,improvement of maternal and child health service levels accounts for the biggest proportion(61.7%),whereas improvement of research level accounts for the least(8.1%).In the four dimensions of policy instruments,mandatory,spontaneous,capacity-building,and incentive tools account for 90%,55%,48%and 42%respectively.According to the trend analysis,integrity of policy system has been continuously improved and the proportion of infant and child care has also increased.Both cross-analysis and trend analysis have showed the strong use of coercive and incentive tools by relevant policies;The use of spontaneous and capacity-building tools is low and decreases over time.Conclusion:Improving the level of maternal and child health services is the core concern of Beijing's early life health policy.However,relatively little attention is paid to the family,infant and child care,and scientific research construction.As for Policy Instruments,mandatory tools are widely used;Incentive Tools and Spontaneous Tools are mainly applied in well-being and soft guidance;insufficient use of Capacity-building Tools.Suggestions:In the future,the policy system should be further improved,which should be targeted and deficiency-mending.It is suggested that more resources should be increased for the family system,more attention should be paid to vulnerable groups early in life,and more financial support should be applied to scientific research on maternal and child health.
3.Micropillar-arrayed surfaces promote transforming growth factor beta 1 induced epithelial to mesenchymal transition by focal adhesion kinase-related signaling in A549 cells.
Lun-Kun MA ; Xing WANG ; Xiao-Li XU ; Jin ZHOU ; Yi LIAO ; Jian-Guo FENG ; Li-Ling TANG
Chinese Medical Journal 2020;134(6):754-756
4.Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study.
Bin SU ; Cheng YAO ; Qing-Xia ZHAO ; Wei-Ping CAI ; Min WANG ; Hong-Zhou LU ; Yuan-Yuan CHEN ; Li LIU ; Hui WANG ; Yun HE ; Yu-Huang ZHENG ; Ling-Hua LI ; Jin-Feng CHEN ; Jian-Hua YU ; Biao ZHU ; Min ZHAO ; Yong-Tao SUN ; Wen-Hui LUN ; Wei XIA ; Li-Jun SUN ; Li-Li DAI ; Tai-Yi JIANG ; Mei-Xia WANG ; Qing-Shan ZHENG ; Hai-Yan PENG ; Yao WANG ; Rong-Jian LU ; Jian-Hua HU ; Hui XING ; Yi-Ming SHAO ; Dong XIE ; Tong ZHANG ; Fu-Jie ZHANG ; Hao WU
Chinese Medical Journal 2020;133(24):2919-2927
BACKGROUND:
Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.
METHODS:
We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.
RESULTS:
At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.
CONCLUSIONS:
The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult
;
Anti-HIV Agents/adverse effects*
;
Antiretroviral Therapy, Highly Active
;
China
;
Drug Therapy, Combination
;
HIV Infections/drug therapy*
;
HIV-1
;
Humans
;
Maleimides
;
Peptides
;
Ritonavir/therapeutic use*
;
Treatment Outcome
;
Viral Load
5.Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis.
Wei ZHU ; Bo-Lun ZHOU ; Li-Juan RONG ; Li YE ; Hong-Juan XU ; Yao ZHOU ; Xue-Jun YAN ; Wei-Dong LIU ; Bin ZHU ; Lei WANG ; Xing-Jun JIANG ; Cai-Ping REN
Journal of Zhejiang University. Science. B 2020;21(2):122-136
Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
Alternative Splicing
;
Carcinogenesis
;
Glycolysis
;
Heterogeneous-Nuclear Ribonucleoproteins/physiology*
;
Humans
;
MicroRNAs/physiology*
;
Neoplasms/pathology*
;
Polypyrimidine Tract-Binding Protein/physiology*
;
RNA, Long Noncoding/physiology*
6.Identification of B (A) Blood Group and Blood Transfusion for patients with B (A) Blood Group.
Chao WANG ; Su-Ping LI ; Xue-Zhong WU ; Min LI ; Xin XING ; Lun-Shan WANG ; Rong LU
Journal of Experimental Hematology 2015;23(4):1147-1151
OBJECTIVETo investigate the serological and molecular biological identification of B(A) blood group and its reasonable method of blood transfusion for patient with B(A) blood group.
METHODSThe blood group of patient was detected by serological method, at the some time, the genotype of patient was detected by using the ABO-TYPE Variant kit and sequence analysis of 6 and 7 exons in ABO gene; the washed O red blood cells were used to cross matching blood of difficultly matching blood by the three step analysis method.
RESULTSThe A weak and B strong agglutination were found in positive type, and A1C(3+), BC(-) were observed in negative type; the molecular biological identification showed B(A)04, 640 A > G; the matching blood main side of washed O red blood cells displayed no agglutination.
CONCLUSIONThe identification and analysis of rare blood or subtype should be very careful; if necessary, the molecular biological detection should carried out; the blood transfusion for patient with rate blood group or subtype should be safe, correct and reasonable.
ABO Blood-Group System ; Blood Grouping and Crossmatching ; Blood Transfusion ; Erythrocyte Count ; Exons ; Genotype ; Humans
7.Studies on flavonoids from Derris eriocarpa.
Lun-xing WANG ; Hong-guo WU ; Hua ZHANG ; Hua-yong LOU ; Guang-yi LIANG ; Wen-wen JIANG ; Zai-chang YANG ; Wei-dong PAN
China Journal of Chinese Materia Medica 2015;40(15):3009-3012
Derris eriocarpa, a traditional Chinese medicine belonging to the family of Leguminosae, is widely distributed mainly over Yunnan, Guangxi and Guizhou of China. Modern pharmacological researches on this herb showed that it had extensive bioactivities, such as promoting urination, removing dampness and cough and reducing inspissated mucus and other biological activities. The extensive studies on the chemical constituents of this plant have resulted in the isolation of triterpenoids, steroids, fatty acid and others, but the flavone compounds haven't reported before. In our further research on the ethyl acetate of this plant, nine flavone compounds were obtained by column chromatography on silica gel, Sephadex LH-20, semi-prep HPLC, polyamide column chromatography and recrystallization for separation and purification. The structures were determined on the basis of extensive spectroscopic analysis, including MS, NMR experiments and comparison with spectroscopic data in the literature, respectively, as diosmetin (1), 3, 3'-di-O-methylquercetin (2), afromosin (3), 6, 3'-dihydroxy-7, 4'-dimethoxyisoflavone (4), odoratin (5), 7, 3'-dihydroxy-8, 4'-dimethoxyisoflavone (6), 6, 4'-dihydroxy-7, 3'-dimethoxyisoflavone (7), 5, 7, 4'-trihydroxy-3, 3', 5'-trimethoxyflavone (8), and alpinumisoflavone (9). All these compounds were isolated from Derris eriocarpa How for the first time. And the in vitro assays showed that compound 2 possessed moderate inhibitory activity against human cancer cells K562 and HEL.
Derris
;
chemistry
;
Flavonoids
;
chemistry
;
isolation & purification
;
pharmacology
;
Humans
;
K562 Cells
8.Establishment of a rabbit model of scoliosis induced by asymmetric load using springs.
Lun-Chao LI ; Xiang LIU ; Qing-An ZHU ; Zhi-Ping HUANG ; Hai-Long REN ; Shuai ZHENG ; Guang-Jun LI ; De-Hong YANG ; Ji-Xing WANG
Journal of Southern Medical University 2015;35(4):594-597
OBJECTIVETo establish rabbit model of scoliosis induced with stable asymmetric lumbar loads.
METHODSScoliosis was induced in 10 two-month-old New Zealand rabbits using 316L stainless steel springs placed between the unilateral transverse processes of L2 and L5. Serial radiographs were documented before and at 1, 4, 8, 9 and 12 weeks after the operation. At weeks, the rabbits were randomly divided into SR group (n=5) with the spring removed and SK group (n=5) without spring removal.
RESULTSAll the rabbits survived the experiment with Cobb angle all greater than 10 degree at the end of the experiment. Significant changes were found in the Cobb angles and kyphotic angles at 1, 4 and 8 weeks after the operation (P<0.05). At 8 weeks, the Cobb angle, the kyphotic angle and the length of the spring were similar between SR and SK groups (P>0.05), and in the 4 weeks following spring removal in SR group, the Cobb angle and the kyphosis decreased significantly compared with those in SK group (P<0.05). Micro-CT showed that the BV/TV of the concave side was greater than that of the convex side. The length of the spring did not show obvious changes during the experiment (P>0.05).
CONCLUSIONSAsymmetric lumbar loading is a convenient, time-saving, and highly reproducible approach for establishing rabbit models of scoliosis.
Animals ; Disease Models, Animal ; Rabbits ; Scoliosis ; physiopathology ; Spine ; pathology
9.The expression of glutamate receptor in hippocampus of neonatal rats with hypoxic-ischemic brain damage
Xiaojuan TANG ; Bin SUN ; Ying WANG ; Xin DING ; Lun YU ; Lixiao XU ; Xing FENG
Journal of Clinical Pediatrics 2014;(4):368-371
Objective To study the expression of Ca-A/K channel-related molecules glutamate receptor 2 and 1(GluR2/1) in hippocampus tissues of neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods A total of 60 7-day-old Sprague-Dawley rats were randomly divided into sham operation group and HIBD group. Hippocampal tissues were obtained at 0 h, 1 h, 6 h, 24 h, 48 h and 72 h after HIBD. The expression of GluR2, GluR1 and autophagy marker protein Beclin-1, LC3 were detected by Western blot assay. Results Edema and focal softening and necrosis were observed 6 h after HIBD in the brains of neonatal rats. Compared with Con group, at each time point, the expression levels of GluR2 were lower while the levels of GluR1, Beclin-1 and LC3 were higher significantly in HIBD group (P<0.05). The protein levels of LC3, Beclin-1, GluR1 and GluR2 in hippocampus tissues of HIBD group were significantly different among different time points after the estab-lishment of HIBD model (F=10.65~701.14, P<0.01). The protein level of GluR2 was decreased from 1 h to 24 h after HIBD and reached the lowest level at 24 h. The levels of GluR1, Beclin-1 and LC3 were increased at 6 h, plateaued at 24 h and remained there until 48 h. The levels of these proteins returned back to the initial level at 72 h. Conclusions Ca-A/K channel-related mol-ecules GluR2 and GluR1 play important roles in the autophagic cell death of hippocampus tissues in neonatal rats with hypoxic-ischemic brain damage.
10.Study on quality of life of asymptomatic HIV infected persons with traditional Chinese medicine.
Li-Ran XU ; Xiao-Ping YANG ; Hui-Jun GUO ; Jin-Wen TU ; Xin DENG ; Cui-E LIU ; Wen-Hui LUN ; Jun-Wen WANG ; Jiang-Rong WANG ; Xing-Hua TAN ; Lu FANG
China Journal of Chinese Materia Medica 2013;38(15):2480-2483
OBJECTIVEStudy on quality of life of asymptomatic HIV infected persons with traditional Chinese medical, which can provide the clinical basis for improving the quality of life.
METHODThis study applied a randomized, double-blind, and placeb-parallel control designed method to select 1 200 persons in the asymptomatic period of HIV infection as the subjects. The subjects were randomly divided into the treatment group and the control group at the ratio of about 2:1. According to the results of monthly differential diagnosis of TCM, the test group and the control group were given homologue Chinese drugs preparations and model Chinese drugs. The total study period was 18 months. Using PRO scale and the world health organization AIDS determination of quality of life short scale form (WHOQOL-HIV-BREF) to investigate asymptomatic HIV infected persons, according to different times, we calculated the total score and each domain score of quality of life of the treatment group and control group, we did statistical analysis.
RESULTForm the PRO scale,we can see that the treatment group showed a trend of stability, compared with the control group with significant statistical difference (P < 0.05) after 6 months; from the WHOQOL-HIV scale analysis, we can see that compared with before treatment, the quality of life of the treatment group was increased, the difference was significant (P < 0.05), but the quality of life of the control quality of life was decreased, the differences was significant (P < 0.05).
CONCLUSIONDialectical therapy of Chinese medicine can significantly improve the patient's quality of life, which can provide the basis for the prevention and control policy formulation and implementation with asymptomatic HIV infected persons.
Asymptomatic Diseases ; Follow-Up Studies ; HIV Infections ; therapy ; Humans ; Medicine, Chinese Traditional ; Quality of Life ; Treatment Outcome

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