1.Research progress in antibody drug therapy for relapsed/refractory diffuse large B-cell lymphoma
Yanyan SUN ; Weichen ZHAO ; Chunyuan HE ; Yimiao XIA ; Wei ZHOU ; Yuanyuan ZHEN ; Junjie JIANG ; Facai WANG
China Pharmacy 2025;36(13):1677-1682
Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease. Although standard first-line regimens can cure >50% of patients, approximately one-third of them develop relapsed/refractory DLBCL (r/r DLBCL). Consequently, immunotherapy targeting molecular abnormalities has become pivotal for managing r/r DLBCL. The results of this review show that with advances in understanding DLBCL pathogenesis and the tumor immune microenvironment, antibody-based therapies have evolved rapidly, progressing from monoclonal antibodies (e.g., rituximab, tafasitamab) to bispecific antibodies(e.g., odronextamab,glofitamab, epcoritamab) and antibody-drug conjugate (e.g., polatuzumab vedotin, loncastuximab tesirine). These engineered agents enhance immune cytotoxicity and tumor-specific targeting, providing novel therapeutic options for r/r DLBCL patients.
2.Bibliometric and visual analysis of Chinese scarlet fever literature
Chunyu ZHAO ; Liu LONG ; Xinjing JIA ; Chunyuan DUAN ; Lisha LIU ; Xiushan ZHANG ; Jinpeng GUO ; Ruizhong JIA ; Wenyi ZHANG ; Yong WANG
Journal of Public Health and Preventive Medicine 2024;35(2):1-5
Objective To analyze the research status and trend of scarlet fever literature in China, and to provide reference for subsequent research. Methods Three major Chinese databases, CNKI, Wanfang, and VIP, as well as Web of Science English database, were used to search for literature related to scarlet fever from 2000 to 2023. Citespace6.2.R2 software was used to statistically analyze the number of publications, authors, institutions and journals, co-cited literature, keyword clustering, and other literature characteristics of the literature. Results From 2000 to 2023, a total of 1 011 Chinese literature were included in the three major Chinese databases. Since 2011, the number of publications had gradually increased, but in recent years, the number of publications had decreased. The organization with the most publications was the Shenyang Center for Disease Control and Prevention. The cluster analysis of key words mainly formed 9 cluster tags, and the high-frequency keywords mainly included epidemic characteristics, epidemiology, incidence rate, etc. A total of 84 English literature were included in the WOS database, with an overall upward trend in publication volume. The institution with the most publications was the China Center for Disease Control and Prevention, and the most frequently cited journal was “LANCET INFECT DIS”.《Resurgence of scarlet fever in China: a 13-year population-based surveillance study》 was the most cited journal. After keyword cluster analysis, 9 cluster labels were mainly formed, and the keywords were mainly outbreak,Hong Kong, and Group A streptococcus. Conclusion Compared with the English literature, which mainly focuses on spatiotemporal aggregation, etiology and strain resistance, Chinese literature focuses more on epidemic surveillance, clinical features and quality nursing.
3.In vitro study on the sealing effect of different shapes of cuff tracheal tubes under the lowest safe pressure
Chunyuan ZHAO ; Ling HUANG ; Zi WEI ; Long CHANG ; Jing LIN ; Chunfeng ZHOU
Chinese Critical Care Medicine 2024;36(1):28-32
Objective:To compare the effectiveness of cylindrical-shaped and conical-shaped cuff catheters for airway closure using different pressure measurement methods at the lowest safe pressure and to guide the clinical application.Methods:Twenty-four patients with endotracheal intubation admitted to the intensive care unit (ICU) of Guangxi Medical University Cancer Hospital from December 2021 to January 2022 were enrolled. Leakage test in vitro was performed on the secretion on the patients' cuff. The needle and plunger from 20 mL syringe was separated, the syringe was sealed with adhesive, and the syringe nozzle was filled thoroughly to create a tracheal model. Consecutively, both cylindrical-shaped and conical-shaped cuff catheters were inserted into the simulated trachea, and the cuff pressure was calibrated to 20 cmH 2O (1 cmH 2O≈0.098 kPa) before commencing the experiment. The viscosity of the secretion on the patients' cuff was classified (grade Ⅰ was watery subglottic secretion, grade Ⅱ was thick subglottic secretion, grade Ⅲ was gel-like subglottic secretion), and the same viscosity secretion was injected into the catheter cuff. Utilizing a self-control approach, intermittent pressure measurement was initially conducted on both the cylindrical-shaped and conical-shaped cuff by improved pressure measurement method (intermittent pressure measurement group), followed by continuous pressure measurement experiment (continuous pressure measurement group). The leakage volume of the three viscosity subglottic secretions and the values of cuff pressure measurement of different shaped cuff catheters at 4, 6, 8 hours of inflation were recorded. Results:A total of 180 retention samples were extracted from 24 patients with tracheal intubation during ventilation, with 90 samples in each of the two groups using different pressure measurement methods, and 30 samples of retention materials with different viscosities in each group. In the intermittent pressure measurement group, at 4 hours of inflation, all samples of secretion with grade Ⅰ and grade Ⅱ on cylindrical-shaped cuff leaked, while 3 samples of secretion with grade Ⅲ also leaked. For conical-shaped cuff, 28 samples of secretion with grade Ⅰ leaked, only 2 samples of secretion with grade Ⅱ leaked, and there was no leak for secretion with grade Ⅲ. At 6 hours of inflation, all samples of the three viscosity secretions on different shaped cuffs leaked. The leakage was gradually increased with the prolongation of inflation time. In the continuous pressure measurement group, at 4 hours of inflation, all samples of secretion with grade Ⅰ on cylindrical-shaped cuff leaked, while 29 samples of secretion with grade Ⅱ leaked, and there was no leak for secretion with grade Ⅲ. For the conical-shaped cuff, 26 samples of secretion with grade Ⅰ leaked, and there was no leak for secretion with grade Ⅱ and grade Ⅲ. At 6 hours of inflation, the conical-shaped cuff still had no leak for secretion with grade Ⅲ. As the inflation time prolonged, the leakage of subglottic secretion on different shaped cuffs in both groups was gradually increased. At 8 hours of inflation, all samples experienced leakage, but the leakage of subglottic secretion on different shaped cuffs in the continuous pressure measurement group was significantly reduced as compared with the intermittent pressure measurement group [leakage for secretion with grade Ⅲ (mL): 1.00 (0.00, 1.25) vs. 2.00 (1.00, 2.00) on the cylindrical-shaped cuff, 1.00 (0.00, 1.00) vs. 2.00 (2.00, 2.00) on the conical-shaped cuff, both P < 0.01]. The values of pressure measurement of cuffs with different shapes at different time points of inflation in the continuous pressure measurement group were within the set range (20-21 cmH 2O). The cuff pressure at 4 hours of inflation in the intermittent pressure measurement group was significantly lower than the initial value (cmH 2O: 18.3±0.6 vs. 20.0±0.0 in the cylindrical-shaped cuff, 18.4±0.6 vs. 20.0±0.0 in the conical-shaped cuff, both P < 0.01), and the cuff pressure in both shaped cuffs showed a significant decrease tendency as inflation time prolonged. However, there was no statistically significant difference in values of pressure measurement between the different shaped cuff catheters. Conclusions:Continuous pressure monitoring devices can maintain the effective sealing of conical-shaped cuff catheters at the lowest safe pressure. When using an improved pressure measurement method for intermittent pressure measurement and/or using a cylindrical cuff catheter, the target pressure should be set at 25-30 cmH 2O, and the cuff pressure should be adjusted regularly.
4.Effect of trichostatin A on lipopolysaccharide-induced injury and apoptosis of human microvascular endothelial cell
Fengsheng WU ; Yu LIU ; Haiying LIU ; Chunyuan WU ; Jieming YU ; Hongxia ZHAO
Chinese Pediatric Emergency Medicine 2023;30(3):203-207
Objective:To investigate the effect of histone deacetylase inhibitor trichostatin A(TSA) on the lipopolysaccharide(LPS)-induced injury and apoptosis of human microvascular endothelial cell(HMEC).Methods:HMECs were used as research cells to establish LPS-induced septic cell model, which were divided into three groups according to different treatments: control group (150 μL of phosphate buffer), LPS group (150 μL of 5 μg/mL LPS), LPS+ TSA group (150 μL of 5 μg/mL LPS and 500 μg/L TSA). After cells of each group were cultured for 24 h and 48 h, the concentration of lactate dehydrogenase(LDH)in the culture supernatant was detected by enzyme-linked immunosorbent assay and the apoptosis rate of HMECs was detected by Annexin V-FTTC/PI staining, then comparison between different groups were made.Results:Compared with the control group, LDH concentration in LPS group increased significantly at 24 h[(4.67±1.27) ng/L vs. (11.57±0.83) ng/L ] and 48 h[(7.93±0.80) ng/L vs. (12.72±0.89) ng/L ]; Compared with LPS group, LDH concentration in LPS + TSA group decreased significantly at 24 h[(6.01±0.29) ng/L ] and 48 h[(5.96±0.27) ng/L ], and the differences were statistically significant ( P<0.05). Compared with the control group, the apoptosis rates of HMEC cells in LPS group were significantly higher at 24 h[(0.92±0.89)% vs. (1.66±0.09)% ] and 48 h[(1.09±0.14)% vs. (5.01±0.16)%]; Compared with LPS group, the apoptosis rate of HMEC cells in LPS + TSA group significantly decreased at 24 h[(1.36±0.01)% ] and 48 h[(4.19±0.23)% ], the differences were statistically significant ( P<0.05). Conclusion:TSA has the protective effect of reducing cell injury and apoptosis in sepsis.
5.Iodine nutrition status of adults and pregnant women in Jianshui and Zhenxiong counties, Yunnan Province
Jiaguo LI ; Hesong WU ; Feng YE ; Zhihua ZHAO ; Liangjing SHI ; Li CHEN ; Wanxian DONG ; Wei YANG ; Chunyuan DENG
Chinese Journal of Endemiology 2023;42(10):803-807
Objective:To investigate the iodine nutritional status of adults and pregnant women in Jianshui County and Zhenxiong County, Yunnan Province.Methods:From May to August 2021, one urban area and one rural area in Jianshui County and Zhenxiong County, Yunnan Province were selected as investigation sites. At least 100 adults (half male and half female) and 100 pregnant women were selected as survey subjects in each investigation site. Random urine samples were collected from all survey subjects once to detect urine iodine, creatinine and sodium contents. Venous blood samples of all pregnant women were collected to detect the serum iodine content, and the 95% medical reference range of serum iodine was established using the percentile method.Results:The medians urinary iodine, creatinine and sodium of adults in Jianshui County and Zhenxiong County were 184.7 μg/L ( n = 432), 12 355.0 μmol/L ( n = 431) and 156.5 mmol/L ( n = 420), respectively. The median urinary iodine of adults in Jianshui County was higher than that in Zhenxiong County (197.3 vs 170.2 μg/L), the difference was statistically significant ( Z = - 2.90, P = 0.003). The median serum iodine of pregnant women in Jianshui County and Zhenxiong County was 92.1 μg/L ( n = 412), with a 95% medical reference value ranged from 45.3 to 183.5 μg/L; the medians urinary iodine, creatinine and sodium of pregnant women were 138.6 μg/L ( n = 413), 12 173.0 μmol/L ( n = 408) and 152.2 mmol/L ( n = 409), respectively. The urinary iodine (154.1 vs 115.8 μg/L), urinary creatinine (13 216.0 vs 11 376.0 μmol/L) and urinary sodium (161.8 vs 141.8 mmol/L) of pregnant women in Jianshui County were higher than those in Zhenxiong County, with statistical differences ( Z = - 5.12, - 2.29, - 4.30, P < 0.05). Conclusion:Adults in Jianshui County and Zhenxiong County are at an appropriate level of iodine, but pregnant women in Zhenxiong County are at an iodine deficiency level.
6.The role of discoid domain receptor 1 on renal tubular epithelial pyroptosis in diabetic nephropathy
Weichen ZHAO ; Chunyuan HE ; Junjie JIANG ; Zongbiao ZHAO ; Hongzhong YUAN ; Facai WANG ; Bingxiang SHEN
The Korean Journal of Physiology and Pharmacology 2022;26(6):427-438
Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes.However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.
7.Screening potential Chinese materia medica and their monomers for treatment diabetic nephropathy based on caspase-1-mediated pyroptosis.
Weichen ZHAO ; Chunyuan HE ; Facai WANG
Journal of Southern Medical University 2020;40(9):1280-1287
OBJECTIVE:
To screen potential traditional Chinese medicine and their active monomer ingredients for treatment of diabetic nephropathy (DN) through the mechanism of caspase-1-mediated pyroptosis.
METHODS:
Using the Chinese Medicine System Pharmacology Analysis Platform (TCMSP), we screened traditional Chinese drugs and their active monomer components targeting caspase-1, and searched for the potential gene targets of the monomer components using GeneCards database. Cytoscape was used to construct the monomer compound-gene target network. Gene ontology (GO) functional enrichment analysis and Kyoto Gene and Gene Encyclopedia (KEGG) pathway enrichment analysis were used to predict the molecular mechanism of the screened traditional Chinese medicine and monomers. In SD rat models of diabetic mellitus (DM), we tested the therapeutic effect of ginsenoside Rh2 (daily dose of 20 mg/kg for 12 weeks) by examining renal pathology with HE staining and detecting the expressions of pyroptosis marker proteins caspase-1, GSDMD, IL-1β and IL-18 in the renal tissues using Western blotting, the serum levels of IL-1β and IL-18 and activities of cathepsin B and cathepsin L.
RESULTS:
Ginsenoside Rh2 could effectively dock with caspase-1 molecule. Fourteen targets were identified in ginsenoside Rh2 target network. GO function enrichment analysis revealed 27 GO terms associated with molecular function (4 terms), cell component (10 terms) and biological process (13 terms). KEGG pathyway enrichment analysis identified 4 signaling pathways involving lysosomes, glycosaminoglycan degradation, galactose metabolism, and sphingolipid metabolism pathways. In the animal experiment, treatment with ginsenoside Rh2 significantly alleviated renal pathologies and down-regulated the expressions of pyroptosis marker proteins (cleaved caspase-1, GSDMD-N, IL-1β and IL-18) ( < 0.05 or 0.01), lowered serum levels of IL-1β and IL-18 ( < 0.01), and enhanced the activities of cathepsin B and cathepsin L in the serum of the diabetic rats.
CONCLUSIONS
Ginsenoside Rh2 may inhibit caspase-1-mediated pyroptosis through the lysosome pathway to improve kidney damages in rat models of DN.
8.Role of Nrf2/HO-1 signal axis in the mechanisms for oxidative stress-relevant diseases.
Tiantian WANG ; Chunyuan CHEN ; Lei YANG ; Zhihui ZENG ; Maojun ZENG ; Wen JIANG ; Lin LIU ; Mingyi ZHAO
Journal of Central South University(Medical Sciences) 2019;44(1):74-80
In the development of oxidative stress-relevant diseases, reactive oxygen species (ROS) removal obstacle or excess production results in the damage of the body tissues and organs. Recent studies have demonstrated that nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) axis played a significant role in anti-oxidative stress. The Nrf2/HO-1 axis counteracts oxidative stress injury by its resistance to inflammation, oxidation, mitochondrial damage and calcium influx, apoptosis, pyroptosis, ferroptosis and autophagy, which provides a theoretical basis for its therapeutic effect on various oxidative stress-relevant diseases in multiple organs (respiratory, cardiovascular, nervous, digestive, urinary and blood systems). Therefore, effective regulation of the Nrf2/HO-1 signal axis can be an important strategy for treatment of oxidative stress-relevant diseases.
Heme Oxygenase-1
;
NF-E2-Related Factor 2
;
Oxidative Stress
;
Reactive Oxygen Species
;
Signal Transduction
9.Effects of recombinant adenovirus Ad-miR-29b2c on HGC-27 cell proliferation and migration.
Ailing LUO ; Chunyuan DU ; Xuemei ZHAO ; Jichao LIANG ; Yong CHEN
Chinese Journal of Biotechnology 2017;33(7):1136-1144
We constructed recombinant adenoviruses expressing miR-29b2c (Ad-miR29b2c), and analyzed their effects on the proliferation and migration of HGC-27 and MGC-803 cells. miR-29b2c gene was amplified by PCR from genomic DNA and cloned into the pAdTrack-CMV vector to create the shuttle plasmid pAdT-29b2c. The recombinant plasmid was verified by restriction enzyme digestion and sequencing. The linearized shuttle vector was mixed with an adenoviral backbone plasmid (pAdEasy-1), followed by cotransformation into competent BJ5183 cells to generate the recombinant plasmid pAd-miR-29b2c. Finally, recombinant adenoviral vectors were generated by transfecting the recombinant plasmid into 293A packaging cell line. HGC-27 and MGC-803 cells were infected with the recombinant adenoviruses expressing pAd-miR-29b2c, then MTT and wound-healing assay were used to analyze the effects of pAd-miR-29b2c on the proliferation and migration of HGC-27 and MGC-803 cells. The miR-29b and miR-29c levels were significantly increased in HGC-27 cells after infected with pAd-miR-29b2c. MTT and wound-healing analysis also revealed a significant decrease in proliferation and migration of HGC-27 and MGC-803 cells compared to the control Ad-GFP-infected cells. Furthermore, western blotting results demonstrated that the protein expression level of δ-catenin was reduced in pAd-miR-29b2c transfected HGC-27 and MGC-803 cells. Taken together, the recombinant adenoviral vector was generated, and it can significantly inhibit the proliferation and migration of HGC-27 and MGC-803 cells.
10.Comparative analysis of HIV disease progression between IDUs with HIV/HCV co-infection and those with HIV infection
Shifu LI ; Jincui FU ; Zaiyou LI ; Chunyuan GUO ; Jie XU ; Jinxian ZHAO ; Liangmin GAO
Chinese Journal of Microbiology and Immunology 2015;(9):692-697
Objective To comparatively analyze the HIV disease progression and the death situa-tion between injecting drug users (IDUs) with HIV infection and those with HIV/HCV co-infection.Meth-ods The counts of CD4+T cells were collected through a retrospective study and the data about death situa-tion were collected with follow-up cards from 2006 to 2014 .A statistical analysis was conducted for the two groups .Results Among the 175 cases with HIV infection , the average value of primary CD 4+T cell counts was 370 cell/μl and 25.71%of them, primary CD4+T cell counts were less than 200 cell/μl.The average change rate of CD4+T cell counts was -1.50 cell/μl in month.The annual mortality rate was 18.18%. Among the 325 cases with HIV/HCV co-infection, the average value of primary CD4+T cell counts was 420 cell/μl and 20.45%of them, primary CD4+T cell counts were less than 200 cell/μl.The average change rate of CD4+T cell counts was -2.76 cell/μl in month.The annual mortality rate was 32.14%.The differ-ences between the groups were significant (P<0.05).Conclusion Compared with patients with HIV infec-tion, those with HIV/HCV co-infection showed significantly decreased CD 4+T cell counts , resulting in a faster disease progression and a faster death .It was urgent for the management department to work out HIV prevention and therapeutic measures .


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