1.Stellate Ganglion Block as an Adjunctive Intervention for Chronic Subjective Tinnitus: Efficacy and Predictive Indicators
Zhicheng LI ; Nan CHENG ; Jibin XING ; Jiawang TIAN ; Jianqi ZHAO ; Huajing TIAN ; Jiayi LIN ; Xiangli ZENG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):276-282
ObjectiveTo explore the efficacy and predictive indicators of stellate ganglion block (SGB) as an adjunctive intervention for chronic subjective tinnitus and accumulate experience for the application of SGB in the clinical treatment of tinnitus. MethodsA retrospective review was conducted on the data of chronic subjective tinnitus patients who received SGB intervention, with unsatisfactory outcomes otherwise. Pure tone audiometry (PTA), tinnitus loudness evaluation and Pittsburgh sleep quality index (PSQI) were used. The tinnitus handicap inventory (THI) scores were compared before and after SGB intervention. Correlation analysis and linear regression equations were employed to identify the potential indicators predicting the effectiveness of SGB intervention. Statistical analysis was performed by SPSS 24.0 software. ResultsBy April 2023, a total of 107 patients with chronic subjective tinnitus had undergone SGB intervention, including 67 male and 40 female, with a mean age of (45.32±11.40) years old and an average tinnitus history of (20.32±24.64) months [16 (12~20)]. Only 7 patients (6.54%) quitted the intervention for personal reasons, which demonstrated good compliance with the intervention. No patients experienced adverse reactions such as infection at the injection site, hematoma, nerve injury, local anesthetic intoxication and so on, which revealed good safety. After SGB intervention, THI scores decreased to below 36 points in 77 patients and decrease by 10 points or more in 12 of the remaining patients, with a total effective rate of 89%. A paired sample t-test showed a significant difference in THI scores before and after SGB intervention (t=15.575, P<0.001), indicating good improvement. Pearson correlation analysis suggested that pre-intervention THI scores and subjective tinnitus loudness were significantly positively correlated with the improvement level of THI scores (P<0.05). Further stepwise linear regression analysis found that "pre-intervention THI scores" had statistical significance (P<0.001), with a regression coefficient of 0.308, predicting a 17.4% improvement level in THI scores. ConclusionsDue to its good and safe short-term effects, SGB intervention can be used as a supplementary option for chronic subjective tinnitus when other interventions are not ideal, especially for patients with higher THI scores. However, further research is needed to clarify the long-term efficacy and underlying mechanisms, in order to establish a more solid theoretical basis for SGB intervention in the treatment of subjective tinnitus.
2.Analysis of HUANG Feng's Medication Rules for Low Back Pain Based on Data Mining
Wen-Xing ZENG ; Min-Hua HU ; Yuan-Lan FENG ; Jing-Tao ZHANG ; Lu-Yao MA ; Hong-Song YAN ; Feng HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):1030-1035
Objective To analyze the medication rules of Professor HUANG Feng for the treatment of low back pain using data mining methods.Methods The information of prescriptions for the effective cases of outpatients with low back pain treated by Professor HUANG Feng were collected and screened.Microsoft Excel 2019 was used to analyze the frequency of medication and the distribution of properties,flavors and meridian tropism of the drugs in the included prescription.IBM SPSS Modeler 18.0 was used for association rule analysis,and IBM Statistics 26.0 was used for cluster analysis.Results A total of 239 prescriptions and 75 Chinese medicines were included.There were 23 high-frequency Chinese medicines with the medication frequency being or over 20 times,and the top 10 Chinese medicines were Glycyrrhizae Radix et Rhizoma,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma,Zanthoxyli Radix,salt-processed Achyranthis Bidentatae Radix,Rehmanniae Radix,Dipsaci Radix,Coicis Semen,and Salviae Miltiorrhizae Radix et Rhizoma.The medicines were mainly warm in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of liver,stomach and spleen meridians.Among the drug combinations obtained from association rule analysis with the top 20 highest support,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma and Zanthoxyli Radix were the core drugs.Cluster analysis yielded 6 clustering combinations.Conclusion For the treatment of low back pain,Professor HUANG Feng follows the principle of"treatment adapting to the climate,individuality,and environment"and"treating the root cause of the disease",usually adopts the drugs for activating blood,moving qi and relieving pain,nourishing the liver and kidney,and also uses the medicines for replenishing qi and strengthening the spleen.The ideas of HUANG Feng for the treatment of low back pain can be used as a reference for the clinical treatment.
3.The Regulatory Function of ADAR1-mediated RNA Editing in Hematological Malignancies
Xing-Yu WAN ; Huan-Ping GUO ; Rui-Hao HUANG ; Xiao-Qi WANG ; Ling-Yu ZENG ; Tao WU ; Lin XIA ; Xi ZHANG
Progress in Biochemistry and Biophysics 2024;51(2):300-308
RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.
4.Effect of lncRNA MIF-AS1 on the malignant biological behavior of prostate cancer cells by regulating the miR-423-5p/PYCR1 axis
Jianbo YANG ; Jichun SHAO ; Zhijun ZENG ; Tao ZHAO ; Xing WANG
The Journal of Practical Medicine 2024;40(18):2544-2549
Objective To investigate the effect of long non-coding RNA(lncRNA)macrophage migration inhibitory factor antisense RNA1(MIF-AS1)on the malignant biological behavior of prostate cancer(PC)cells by regulating the miR-423-5p/pyrroline-5-carboxylic acid reductase 1(PYCR1)axis.Methods PC3 cells were cultured in vitro to knock down the expression of MIF-AS1 or down-regulate the expression of miR-423-5p.The expression of MIF-AS1,miR-423-5p and PYCR1 mRNA in tumor tissues and adjacent tissues and cells of PC patients were detected.The cell proliferation,apoptosis,migration,and invasion were detected and the expression of PYCR1 protein was detected by Western blot.The relationships between miR-423-5p,IF-AS1 and PYCR1 were verified.Results The MIF-AS1 and PYCR1 mRNA were observed to be highly expressed in the tumor tissues,while miR-423-5p was lowly expressed.Silenced MIF-AS1 inhibited the proliferation,migration and invasion of PC3 cells and up-regulated miR-423-5p induced cell apoptosis(P<0.05).Inhibition of miR-423-5p expression reversed the inhibitory effect of silencing MIF-AS1 on malignant behavior of PC3 cells(P<0.05).miR-423-5p was correlated with MIF-AS1 and PYCR1 by targeted regulation.Conclusion Silencing MIF-AS1 may inhibit the expression of PYCR1 by up-regulating miR-423-5p,thereby inhibiting the malignant behavior of PC cells.
5.Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion
Zhong-You ZENG ; Ping-Quan CHEN ; Xing ZHAO ; Hong-Fei WU ; Jian-Qiao ZHANG ; Xiang-Qian FANG ; Yong-Xing SONG ; Wei YU ; Fei PEI ; Shun-Wu FAN ; Guo-Hao SONG ; Shi-Yang FAN
China Journal of Orthopaedics and Traumatology 2024;37(1):33-44
Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4%.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P<0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)%to the latest follow-up(11.30±3.27)%,and there was statistically significant different.The complication rate was 31.3%(45/144),and the reoperation rate was 9.72%(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14%(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.
6.Quantitative analysis of the characteristics and influencing factors of hearing loss among workers exposed to noise in Tianjin
Shuying WANG ; Pei LI ; Ya GAO ; Yanming ZHOU ; Xing WANG ; Qiang ZENG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(5):346-349
Objective:To analyze the characteristics of high-frequency average hearing loss in both ears of noise exposed workers in Tianjin in 2020, and quantitatively analyze the influencing factors of high-frequency hearing loss in both ears of workers.Methods:In March 2023, Collect and organize basic information about noise-hazardous enterprises and personal information of workers exposed to noise. Data from the Tianjin Occupational Disease and Health Hazard Factors Information Monitoring System from January 2020 to December 2020, and analyze the impact of basic information of employees, enterprise size, regional distribution, industry category, and economic type on the high-frequency average hearing loss of workers during work. Apply logistic regression to quantitatively analyze the influencing factors of abnormal high-frequency average hearing threshold of noise exposed workers.Results:The size, economic type, industry category, and regional distribution of enterprises, as well as the gender, age, length of service of workers, have an impact on the abnormal high-frequency average hearing threshold of noise exposed workers (χ 2=733.56、3 497、27、1352.84、1197.62、2570.59、22.30、506.60, P<0.001) . Quantitative analysis using a logistic regression model showed that in the basic information of workers, noise exposed workers were male ( OR=2.500, P<0.001) and aged 30-39, 40-49, and 50-59 years ( OR=1.33, P<0.001; OR=1.68, P<0.001; OR=1.52, P< 0.001) , with a length of service of 4 to<10 years and≥10 years ( OR=1.08, P<0.001; OR=1.615, P<0.001) being the influencing factors for high-frequency hearing loss in both ears of noise exposed workers; In terms of enterprise characteristics, medium-sized, small and micro enterprises ( OR=1.12, P<0.001; OR=1.75, P<0.001; OR=2.09, P<0.001) , enterprises located in the fourth district around the city ( OR=1.268, P<0.001) , and enterprises with economic types of collective economy, other economy, private economy, Hong Kong, Macao and Taiwan investment, shareholding system, and other industry economies ( OR are all >1, P<0.001) are all factors affecting high-frequency hearing loss in noise exposed personnel. Conclusion:Noise is a common occupational hazard factor in Tianjin's enterprises, especially for workers in micro enterprises who face a high risk of hearing abnormalities. Therefore, enterprises need to strengthen the management and intervention of noise operations to prevent the occurrence of hearing loss in workers.
7.Quantitative analysis of the characteristics and influencing factors of hearing loss among workers exposed to noise in Tianjin
Shuying WANG ; Pei LI ; Ya GAO ; Yanming ZHOU ; Xing WANG ; Qiang ZENG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(5):346-349
Objective:To analyze the characteristics of high-frequency average hearing loss in both ears of noise exposed workers in Tianjin in 2020, and quantitatively analyze the influencing factors of high-frequency hearing loss in both ears of workers.Methods:In March 2023, Collect and organize basic information about noise-hazardous enterprises and personal information of workers exposed to noise. Data from the Tianjin Occupational Disease and Health Hazard Factors Information Monitoring System from January 2020 to December 2020, and analyze the impact of basic information of employees, enterprise size, regional distribution, industry category, and economic type on the high-frequency average hearing loss of workers during work. Apply logistic regression to quantitatively analyze the influencing factors of abnormal high-frequency average hearing threshold of noise exposed workers.Results:The size, economic type, industry category, and regional distribution of enterprises, as well as the gender, age, length of service of workers, have an impact on the abnormal high-frequency average hearing threshold of noise exposed workers (χ 2=733.56、3 497、27、1352.84、1197.62、2570.59、22.30、506.60, P<0.001) . Quantitative analysis using a logistic regression model showed that in the basic information of workers, noise exposed workers were male ( OR=2.500, P<0.001) and aged 30-39, 40-49, and 50-59 years ( OR=1.33, P<0.001; OR=1.68, P<0.001; OR=1.52, P< 0.001) , with a length of service of 4 to<10 years and≥10 years ( OR=1.08, P<0.001; OR=1.615, P<0.001) being the influencing factors for high-frequency hearing loss in both ears of noise exposed workers; In terms of enterprise characteristics, medium-sized, small and micro enterprises ( OR=1.12, P<0.001; OR=1.75, P<0.001; OR=2.09, P<0.001) , enterprises located in the fourth district around the city ( OR=1.268, P<0.001) , and enterprises with economic types of collective economy, other economy, private economy, Hong Kong, Macao and Taiwan investment, shareholding system, and other industry economies ( OR are all >1, P<0.001) are all factors affecting high-frequency hearing loss in noise exposed personnel. Conclusion:Noise is a common occupational hazard factor in Tianjin's enterprises, especially for workers in micro enterprises who face a high risk of hearing abnormalities. Therefore, enterprises need to strengthen the management and intervention of noise operations to prevent the occurrence of hearing loss in workers.
8.Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment
ZENG SHENG ; XING SHAOQIANG ; ZHANG YIFEI ; WANG HAIFENG ; LIU QIAN
Journal of Zhejiang University. Science. B 2024;25(7):557-567
Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery,radiotherapy,and chemotherapy,with some promising results.It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells.However,the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity.Recently,nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens,activating targeted T cells,modulating the immunosuppressive tumor microenvironment,and improving the treatment efficacy.Bacillus Calmette-Guérin(BCG)is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis,which was first reported to have antitumor activity in 1927.BCG therapy can activate the immune system by inducing various cytokines and chemokines,and its specific immune and inflammatory responses exert antitumor effects.BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer,which effectively improved immune antitumor activity and prevented tumor recurrence.More recently,nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses.In this study,we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.
9.Improvement effect of Xuebijing on brain tissue injury and Th17/Treg immune imbalance in cerebrospinal fluid in NMDA receptor encephalitis model mice
Lin CHEN ; Limin YAN ; Huaijie XING ; Min CHEN ; Xiaoyan LI ; Chaosheng ZENG
Journal of Jilin University(Medicine Edition) 2024;50(3):697-707
Objective:To discuss the effect of Xuebijing on brain tissue damage and immune imbalance of helper T lymphocyte 17(Th17)/regulatory T lymphocyte(Treg)in cerebrospinal fluid(CSF)of the N-methyl-D-aspartate(NMDA)receptor encephalitis model mice,and to clarify its therapeutic effect.Methods:Sixty healthy male C57BL/6J mice were randomly divided into control group,model group,low dose of Xuebijing group,and high dose of Xuebijing group,and there were 15 mice in each group.Except for control group,the mice in the other three groups were injected with the antigen combined with immunostimulation to establish the NMDA receptor encephalitis models.The mice in low and high doses of Xuebijing groups were injected intraperitoneally with 5 and 10 mL·kg-1 of Xuebijing injection,respectively.HE staining was used to observe the pathomorphology of brain tissue of the mice in various groups;TUNEL assay was used to detect the apoptotic rates of the neurons in hippocampus CA1 region of brain tissue of the mice in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of interleukin(IL)-6,IL-10,IL-17,and transforming growth factor β(TGF-β)in serum of the mice in various groups;flow cytometry was used to detect the percentages of Th17 and Treg cells in CSF of the mice in various groups;Western blotting method was used to detect the expression levels of retinoic acid-related orphan receptor γt(RORγt),forkhead box protein 3(Foxp3),IL-10,and IL-17 proteins in brain tissue of the mice in various groups;immunohistochemistry method was used to detect the rates of IL-17 and Foxp3 positive cells in brain tissue of the mice in various groups.Results:The HE staining results showed that the hippocampus CA1 region of brain tissue of the mice in control group had a clear structure without obvious lesions;compared with control group,the mice in model group showed partial pyramidal cell shrinkage,elongation of apical dendrites,loss of a few neurons,and sparse tissue in the hippocampus CA1 region of brain tissue;compared with model group,the mice in low and high doses of Xuebijing groups showed that the damage of the cells in the hippocampus CA1 region of brain tissue was decreased,and the morphological recovery,more orderly arrangement,and more significant improvement could be seen in hippocampus CA1 region of the mice in high dose of Xuebijing group.The TUNEL assay results showed that compared with control group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in model group was significantly increased(P<0.05);compared with model group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05);compared with low dose of Xuebijing group,the apoptotic rate of the neurons in hippocampus CA1 region of brain tissue of the mice in high dose of Xuebijing group was significantly decreased(P<0.05).The ELISA results showed that compared with control group,the levels of IL-6 and IL-17 in serum of the mice in model group were significantly increased(P<0.05),while the levels of IL-10 and TGF-β were significantly decreased(P<0.05);compared with model group,the levels of IL-6 and IL-17 in serum of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the levels of IL-10 and TGF-β were significantly increased(P<0.05);compared with low dose of Xuebijing group,the levels of IL-6 and IL-17 in serum of the mice in high dose of Xuebijing group were significantly decreased(P<0.05),while the levels of IL-10 and TGF-β were significantly increased(P<0.05).The flow cytometry results showed that compared with control group,the percentage of CD4+IL-17A+Th17 cells in CSF of the mice in model group was significantly increased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly decreased(P<0.05);compared with model group,the percentages of CD4+IL-17A+Th17 cells in CSF of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly increased(P<0.05);compared with low dose of Xuebijing group,the percentage of CD4+IL-17A+Th17 cells in CSF of the mice in high dose of Xuebijing group was significantly decreased(P<0.05),while the percentage of CD25+Foxp3+Treg cells was significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in model group were significantly increased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly decreased(P<0.05);compared with model group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly increased(P<0.05);compared with low dose of Xuebijing group,the expression levels of RORγt and IL-17 proteins in brain tissue of the mice in high dose of Xuebijing group were significantly decreased(P<0.05),while the expression levels of Foxp3 and IL-10 proteins were significantly increased(P<0.05).The immunohistochemistry results showed that compared with control group,the rate of IL-17 positive cells in brain tissue of the mice in model group was significantly increased(P<0.05),while the rate of Foxp3 positive cells was significantly decreased(P<0.05);compared with model group,the rates of IL-17 positive cells in brain tissue of the mice in low and high doses of Xuebijing groups were significantly decreased(P<0.05),while the rates of Foxp3 positive cells were significantly increased(P<0.05);compared with low dose of Xuebijing group,the rate of IL-17 positive cells in brain tissue of the mice in high dose of Xuebijing group was significantly decreased(P<0.05),while the rate of Foxp3 positive cells was significantly increased(P<0.05).Conclusion:Xuebijing can effectively ameliorate the brain tissue injury,regulate the cytokine levels,and intervene in immune imbalance of Th17/Treg in the mice with anti-NMDA receptor encephalitis.
10.Effect of Aspergillus fumigatus on DNA damage and IL-33 expression in human bronchial epithelial cells and its mechanism
Qiao WANG ; Ziling ZENG ; Xing WANG ; Ning MA ; Zhibin WANG ; Guofeng XU ; Xiefang YUAN ; Xiaoyun WANG ; Yuejiao LI ; Hongmei TANG ; Yun ZHANG
Journal of Jilin University(Medicine Edition) 2024;50(5):1205-1216
Objective:To discuss the effect of Aspergillus fumigatus(Af)on DNA damage and interleukin(IL)-33 expression in the human bronchial epithelial cells,and to clarify its related mechanism.Methods:Different concentrations(1,5,and 10 mg·L-1)of Af were used to stimulate the bronchial epithelial BEAS-2B cells to select the appropriate stimulation concentration.When the BEAS-2B cells were treated with N-acetylcysteine(NAC)and Af,the cells were divided into control group,Af group,NAC group,and Af+NAC group.When the BEAS-2B cells were treated with DNA double-strand break repair inhibitor NU7441 and Af,the cells were divided into control group,Af group,NU7441 group,and Af+NU7441 group.The comet assay was used to detect the percentages of comet tail DNA of cells in various groups;immunofluorescence method was used to detect the expression levels of DNA damage-related protein phosphorylated H2AX(yH2AX)in the cells in various groups;2,7-dichlorofluorescein diacetate(DCFH-DA)fluorescence probe was used to detect the levels of reactive oxygen species(ROS)in the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukih-33(IL-33),thymic stromal lymphopoietin(TSLP),and interleukih-25(IL-25)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated nuclear factor κB(p-NF-κB),phosphorylated ataxia telangiectasia mutated(p-ATM),and γH2AX proteins in the cells in various groups.Results:Compared with control group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 1 mg·L-1 Af group showed no significant difference(P>0.05),while the percentage of comet tail DNA and the expression level of γH2AX in the cells in 5 mg·L-1 Af group were significantly increased(P<0.01);compared with 5 mg·L-1 Af group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 10 mg·L-1 Af group were significantly increased(P<0.01).Compared with control group,the ROS levels in the bronchial epithelial cells in 1 mg·L-1 Af group was significantly increased(P<0.05);compared with 1 mg·L-1 Af group,the ROS level in the cells in 5 mg·L-1 Af group was significantly increased(P<0.01);compared with 5 mg·L-1 Af group,the ROS level in the cells in 10 mg·L-1 Af group was significantly increased(P<0.05).After treatment of NAC,compared with Af group,the percentage of comet tail DNA(P<0.01),the expression level of γH2AX(P<0.05),and the ROS level(P<0.01)in the cells in Af+NAC group were significantly decreased;after treatment of NU7441,compared with Af group,the percentage of comet tail DNA and the expression level of yH2AX in the cells in Af+NU7441 group were significantly increased(P<0.01).The RT-qPCR results showed that after treatment of NAC,compared with control group,the expression level of IL-33 mRNA in the cells in Af group was significantly increased(P<0.05);compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NAC group was significantly decreased(P<0.05);after treatment of NU7441,compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NU7441 group was significantly increased(P<0.05).The Western blotting results showed that after treatment of NAC,compared with control group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af group were significantly increased(P<0.05);after treatment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NAC group were significantly decreased(P<0.05);After treat ment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NU7441 group were significantly increased(P<0.05).Conclusion:Af promotes the IL-33 expression in the human bronchial epithelial cells by causing DNA damage,and its mechanism may be related to the activation of ATM/NF-κB signaling pathway.

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