1.Effect of Qinghua Yichang Formula (清化益肠方) on NLRP3 Inflammasome in Intestinal Tissue of Mice with Acute Radiation-Induced Intestinal Injury
Yuanyuan QIN ; Lingyan ZHU ; Li LI ; Bowen CHU ; Zequn JIANG ; Mianhua WU
Journal of Traditional Chinese Medicine 2024;65(16):1695-1702
ObjectiveTo explore the effect and possible molecular mechanism of Qinghua Yichang Formula (清化益肠方, QYF) in treating acute radiation-induced intestinal injury mice via NOD-like receptor thermal protein domain associated protein 3 (NLRP3). MethodsSixty C57BL/6J mice were randomly divided into control group, model group, pre-modeling medication group, post-modeling medication group, inhibitor group, and QYF plus inhibitor group, with 10 mice in each group.Except for the control group, the other five groups were irradiated with a single full dose to establish the acute radiation-induced intestinal injury mice model. The pre-modeling medication group and the QYF plus inhibitor group were continuously given 4 g/ml of QYF decoction by gavage before modeling, 0.2 ml each time, once a day for 7 days. The post-modeling medication group, pre-modeling medication group and QYF plus inhibitor group were given 4 g/ml of QYF decoction for 14 days after modeling. The control group, model group and inhibitor group were given 0.2 ml of normal saline once a day for 14 consecutive days. Two hours after irradiation, the inhibitor group and the QYF plus inhibitor group were given an intraperitoneal injection of 0.2 ml of the NLRP3 inhibitor MCC950 (concentration: 10 mg/kg), once every two days. To observe the pathological changes in intestinal tissues, hematoxylin-eosin (HE) staining was used. Western blotting and RT-qPCR were used to detect the protein and mRNA expression levels of NLRP3 in intestinal tissues. Immunohistochemistry was used to detect the expression level of NLRP3, Caspase-1 and GSDMD in intestinal tissues. The proportion of CD4+ and CD8+ T cells in the spleens of mice were detected by flow cytometry. ELISA was used to determine the levels of IFN-γ, IL-18, and IL-1β in mice serum. ResultsHE staining showed no lesions in the intestinal tissue of mice in the control group. The mice in the model group had shortened intestinal villi, thinned mucosal layers, multifocal mucosal necrosis in the lamina propria, and local neutrophil infiltration. The pathological damage of intestinal tissue of mice in each medication group was improved to varied degrees, among which the QYF plus inhibitor group showed most obvious improvement. Compared to those in the control group, the protein and mRNA expression levels of NLRP3 in the intestinal tissue of mice in the model group significantly increased, with higher NLRP3, Caspase-1, and GSDMD protein expression in the intestinal tissue, increased proportion of CD4+ T cells in spleen, decreased proportion of CD8+ T cells, and increased levels of IFN-γ, IL-18 and IL-1β in serum (P<0.05). Compared to those in the model group, the above indicators in the other medication groups were all improved (P<0.05).The NLRP3, Caspase-1, and GSDMD proteins in the pre-modeling medication group were lower than those in the post-modeling medication group (P<0.05); and the NLRP3 mRNA level in the QYF plus inhibitor group was lower than that in the inhibitor group (P<0.05). ConclusionQYF may play a role in preventing and treating acute radiation-induced intestinal injury by inhibiting the expression of NLRP3.
2.Exploration on the Mechanism of Marsdenia tenacissima against Breast Cancer Based on Network Pharmacology and Experimental Verification
Juan ZHAO ; Zhaoyang MENG ; Qinfang ZHU ; Lanyi WEI ; Lingyan XU ; Yonglong HAN ; Junjun CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):24-32
Objective To explore the mechanism of Marsdenia tenacissima in the treatment of breast cancer through network pharmacology and experimental verification.Methods Literature retrieval was conducted to obtain the active components of Marsdenia tenacissima.The SwissTargetPrediction database was used to predict the potential targets of these active components.Targets of breast cancer were obtained from GeneCards,GEPIA2,OMIM,PharmGKB and TTD databases.The intersection targets were obtained,and a Marsdenia tenacissima-breast cancer-targets network was constructed using Cytoscape 3.9.0 software.The core targets were identified through protein-protein interaction(PPI)network analysis,followed by GO and KEGG pathway enrichment analysis to screen relevant signaling pathways.Molecular docking validation was performed for the top 10 key targets and major active components.The human breast cancer cell line MDA-MB-231 was treated with Marsdenia tenacissima injection in vitro.Cell proliferation ability was detected by CCK-8 assay and colony formation assay.Cell apoptosis was detected by Calcein-AM/PI staining and flow cytometry.Cell migration ability was detected by Transwell assay.Western blot experiment was used to validate the PI3K-AKT signaling pathway.Results Totally 37 active components and 276 potential targets against breast cancer were screened from Marsdenia tenacissima,including 11alpha-O-Benzoyl-12beta-O-acetyl tenacigenin B,Caffeic acid,Drevogenin A and Kaempferol.25 core targets were screened by PPI network such as AKT1,EGFR,TNF,CTNNB1 and IL-6,which mainly affected the estrogen signaling pathway,ErbB signaling pathway,HIF-1 signaling pathway and PI3K-AKT signaling pathway,etc.The molecular docking results showed that the main active components of Marsdenia tenacissima exhibited good binding activities with the core targets AKT1,ALB,CASP3,ESR1 and TNF.The results of in vitro experiments showed that Marsdenia tenacissima injection could inhibit the proliferation and migration ability of MDA-MB-231 cells(P<0.01,P<0.001)and induce apoptosis(P<0.001),as well as inhibit the activation of PI3K-AKT signaling pathway(P<0.05,P<0.01).Conclusion Marsdenia tenacissima may exert its anti-breast cancer effects through multiple targets and pathways,and the mechanism may be related to the inhibition of PI3K-AKT signaling pathway.
3.Analyzing the correlation between HLA-DQA1 gene and clinical characteristics of patients with Sj?gren's syndrome
Hui XU ; Lingyan ZHU ; Kai ZHAO ; Hui WANG ; Yongfu WANG
China Modern Doctor 2024;62(19):80-83,110
Objective To investigate the correlation between human leucocyte antigen-DQA1(HLA-DQA1)and clinical characteristics of patients with Sj?gren's syndrome(SS).Methods A total of 242 SS patients admitted to the First Affiliated Hospital of Baotou Medical College from August 2022 to August 2023 were selected as the study objects.According to the HLA-DQA1 test results,the patients were divided into HLA-DQA1 positive group(n=147)and HLA-DQA1 negative group(n=95).The clinical manifestations,laboratory indicators,labial gland biopsy and disease activity were compared between two groups.Receiver operating characteristic curve was used to analyze the diagnostic value of HLA-DQA1 for disease activity in SS patients.Results The proportion of dry mouth,dry eye and purpura,the proportion of anti-SSA antibodies,anti-SSB antibodies,antinuclear antibody(ANA)positive and the level of immunoglobulin G in HLA-DQA1 positive group were significantly higher than those in HLA-DQA1 negative group(P<0.05),and the hemoglobin level was significantly lower than that in HLA-DQA1 negative group(P<0.05).The disease activity of HLA-DQA1 positive group was significantly higher than that of HLA-DQA1 negative group(P<0.05).The areas under the curve of HLA-DQA1,anti-SSA antibody and anti-SSB antibody to determine the disease activity of SS patients were 0.593,0.534 and 0.593,respectively.The area under the curve of disease activity of SS patients judged by the three indexes combined was 0.638.Conclusion HLA-DQA1 is correlated with the disease activity of SS patients.In HLA-DQA1 positive patients,dry mouth,dry eyes,hyperglobulinemia,anemia and purpura were more obvious.Meanwhile,the positive rates of anti-SSA/SSB antibodies and ANA were higher,suggesting that HLA-DQA1 expression is helpful in judging the disease of SS patients.
4.Application value of heparin binding protein,NLR,LMR,and PLR in immune function reconstruction evaluation in HIV/AIDS patients
Lingyan HE ; Jinchuan SHI ; Jianghao CHENG ; Mingli ZHU
China Modern Doctor 2024;62(32):52-55
Objective To explore the application value of heparin binding protein(HBP),neutrophil to lymphocyte ratio(NLR),lymphocyte to monocyte ratio(LMR),and platelet to lymphocyte ratio(PLR)in the evaluation of immune function reconstruction in human immunodeficiency virus(HIV)infected individuals/acquired immunodeficiency syndrome(AIDS)patients.Methods Collect 138 HIV/AIDS patients from the Outpatient Department of Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University from January 1,to June 30,2023.According to CD4+T lymphocyte counts after antiretroviral treatment,categorize patients into groups with good immune function reconstruction(n=108)and poor immune function reconstruction(n=30).Compare the levels of HBP,NLR,LMR,and PLR between two groups,receiver operating characteristic(ROC)curve was used to evaluate the application value of HBP,NLR,LMR,and PLR in the reconstruction of patient immune function.Results The NLR and PLR of group with good immune function reconstruction was significantly higher than that of group with poor immune function reconstruction(P<0.05).The LMR of group with good immune function reconstruction were significantly lower than those of group with poor immune function reconstruction(P<0.05).The HBP between two groups was no significant differences(P>0.05).LMR had the best efficacy in evaluating whether immune function reconstruction was good in HIV/AIDS patients area under the curve(AUC)=0.803,PLR was the second(AUC)=0.796,NLR was poor(AUC)=0.728.Conclusion NLR,LMR,and PLR are closely related to the immune function of HIV/AIDS patients and can be used as detection indicators to evaluate whether the immune function reconstruction of HIV/AIDS patients is good.
5.Effects of mindfulness-based stress reduction on stress response and job burnout of head nurses in the context of Coronavirus disease 2019
Haihui ZHU ; Lijuan LI ; Wei YUAN ; Kun HOU ; Lingyan CAO ; Lidan ZHOU
Chinese Journal of Practical Nursing 2023;39(7):491-497
Objective:To explore the efforts of applying mindfulness stress reduction therapy in alleviating stress reactions and burnout among head nurses in the context of the Coronavirus disease 2019 (COVID-19).Methods:This was a quasi experimental study. In June 2021, 109 head nurses with mild or above burnout measured by Maslach Burnout Inventory (MBI) from 12 hospitals in Zhangjiagang City were selected as the research objects to implement mindfulness-based stress reduction therapy for 8 weeks, and the scores of the Five Facet Mindfulness Question-naire (FFMQ), Stress Response Questionnaire (SRQ) and MBI of the head nurses were compared before and after the intervention.Results:The five dimensions of observation, description, perceived action, non-judgment, and non-response and the total scores of the FFMQ were (26.28 ± 1.32), (26.94 ± 1.29), (25.49 ± 0.99), (25.45 ± 1.05), (23.48 ± 1.01), and (127.63 ± 3.78) of the post-intervention, which were higher than the pre-intervention scores of (25.04 ± 1.37), (25.04 ± 1.37), (25.37 ± 1.18), (24.15 ± 1.00), (24.09 ± 0.98), (22.26 ± 1.04), and (120.90 ± 4.06), with statistically significant differences ( t values were -39.21- -15.36, all P<0.01). The three dimensions of emotional, somatic, and behavioral responses and total scores of the post-intervention SRQ were (27.70 ± 6.12), (20.75 ± 4.20), (15.19 ± 3.11), and (65.99 ± 12.43), respectively, lower than the pre-intervention scores of (29.19 ± 6.91), (21.86 ± 5.20), (16.48 ± 4.16), and (70.12 ± 15.97), with statistically significant differences ( t values were 5.70-9.33, all P<0.01); the scores of dimensions of emotional exhaustion and depersonalization in post-intervention MBI were (26.24 ± 4.60) and (5.96 ± 1.25), lower than the pre-intervention scores of (29.66 ± 6.02) and (6.90 ± 1.59). The post-intervention scores of personal fulfillment (32.37 ± 5.02), higher than the pre-intervention scores of (28.60 ± 6.04), all with statistically significant differences ( t=15.36, 13.50, -9.65, all P<0.01). Conclusions:The implementation of mindfulness stress reduction therapy for the head nurses can relieve their work pressure due to the prevention and control of the COVID-19 epidemic, reshape their healthy psychology, and reduce job burnout.
6.Correlation between atmospheric nitrogen oxides and nitrogen dioxide acute exposure and outpatient visits of pediatric respiratory diseases
Xinpeng GUAN ; Hongbing XU ; Jiakun FANG ; Yutong ZHU ; Lingyan LIU ; Qian ZHAO ; Xiaoming SONG ; Baoping XU ; Wei HUANG
Journal of Preventive Medicine 2023;35(3):185-189
Objective :
To examine the association between acute exposure to traffic-related air pollutants (TRAP) NOX and NO2 and outpatient visits of pediatric respiratory diseases.
Methods :
Data regarding outpatient visits to Department of Respiratory Diseases of Beijing Children's Hospital from 2015 to 2020 were collected, and the concentrations of nitrogen oxides (NOX), nitrogen dioxide (NO2) and other TRAP were collected from the surveillance sites assigned by the Peking University Health Science Center. A time-stratified case-crossover design was employed, and a conditional logistic regression model was created to examine the association between NOX and NO2 acute exposure and outpatient visits of pediatric respiratory diseases.
Results :
The daily mean outpatient visits of pediatric respiratory diseases were 571 (interquartile range, 554) person-times among children at ages of 0 to 14 years in Beijing Children's Hospital from 2015 to 2020, and the daily mean outpatient visits for upper respiratory tract infections (URI), bronchitis, and pneumonia were 265 (interquartile range, 282), 143 (interquartile range, 178) and 128 (interquartile range, 120) person-times, respectively. The daily mean concentrations of atmospheric NOX and NO2 were 67.8 (interquartile range, 50.7) and 49.3 (interquartile range, 30.7) μg/m3, respectively. Conditional logistic regression analysis showed the largest lagged effect of NOX and NO2 on pediatric respiratory diseases at cumulative lags of 0 to 7 days. An increase in NOX concentrations by an interquartile range resulted in the excess risks of URI, bronchitis and pneumonia by 6.87% (95%CI: 6.37%-7.38%), 7.25% (95%CI: 6.51%-7.99%), and 5.51% (95%CI: 4.69%-6.33%), and an increase in NO2 concentrations by an interquartile range resulted in excess risks of URI, bronchitis and pneumonia by 5.71% (95%CI: 5.12%-6.31%), 5.32% (95%CI: 4.51%-6.14%), and 4.83% (95%CI: 3.91%-5.75%), respectively. NOX and NO2 presented a more remarkable effect on outpatient visits of pediatric respiratory diseases among children at ages of over 5 years.
Conclusion
NOx and NO2 acute exposure may increase the outpatient visits of pediatric respiratory diseases.
7.Progress of targeted drugs for treatment of diffuse large B-cell lymphoma
Jiajin WU ; Lingyan PING ; Jun ZHU ; Yuqin SONG
Journal of Leukemia & Lymphoma 2023;32(3):143-146
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive lymphoma. The relapsed/refractory DLBCL patients have poor outcomes and DLBCL is still lack of effective treatment standard regimens. How to effectively treat relapsed/refractory DLBCL patients has become a research hotspot, and the current treatment methods include bispecific antibody therapy, chimeric antigen receptor T-cell (CAR-T) therapy, antibody-drug conjugates (ADC) therapy. This paper reviews the progress of targeted drugs/cell treatment for DLBCL at the 64th American Society of Hematology annual meeting.
8.A study on sensory processing characteristics of preschool children with autism spectrum disorder
Lian JIANG ; Liting CHU ; Chenhuan MA ; Lingyan CHEN ; Mengfan LI ; Lizhu PAN ; Peiying ZHU ; Yu WANG
Shanghai Journal of Preventive Medicine 2022;34(10):955-959
ObjectiveTo explore the sensory processing characteristics of preschool children with autism spectrum disorder (ASD), and to provide a theoretical basis for early screening and intervention training of ASD. MethodsA total of 215 preschool children with ASD and170 typically developed (TD) children were investigated with a basic situation questionnaire and sensory processing measure (SPM). The two groups were stratified according to age and gender, and the differences of scores in sensory domains were compared to analyze the sensory processing characteristics of preschool children with ASD. ResultsThe scores of social participation, vision, hearing, touch, taste and smell, body awareness, balance and motion, planning and ideas, and total sensory system in children with ASD were all higher than those in children with TD (all P<0.01). The highest degree of abnormality was found in hearing and the lowest degree in taste and smell in children with ASD. The results of Spearman correlation analysis showed that in the 4-year-old and 5-year-old children with ASD, the scores of vision (rs=-0.200, P= 0.033) and hearing (rs=-0.194, P=0.040) decreased with age. There was no correlation between the scores of other developmental quotients and age (all P>0.05). Boys and girls with ASD had higher scores in all developmental quotients than TD children (P<0.01). However, there was no significant gender difference in any developmental quotients of ASD children (all P>0.05). ConclusionSensory processing abnormalities are common in preschool children with ASD, which are different from those of TD children in multiple sensory domains. Sensory processing abnormalities may be used as an indicator for early screening of ASD, and it is necessary to conduct corresponding intervention training for sensory processing abnormalities in children with ASD.
9.Short-term exposure to ambient ozone associated with cardiac arrhythmias in healthy adults
Liu LINGYAN ; Zhu YUTONG ; Xu HONGBING ; Wang YANG ; Wang TONG ; Zhao QIAN ; Zhang YI ; Chen JIE ; Liu SHENGCONG ; Yi TIECI ; Wu RONGSHAN ; Liu SHUO ; Song XIAOMING ; Li JIANPING ; Huang WEI
Global Health Journal 2022;6(1):6-18
Objective:The exact biological mechanism whereby exposure to ambient ozone(O3)may contribute to clinical onset of cardiovascular events remains unclear.In this study,we aim to examine the impacts of O3 exposure on cardiac arrhythmias and potential pathways involved through autonomic dysfunction and myocardial injury.Methods:Seventy-three non-smoking healthy adults were followed with 4 repeated measurements of 24-hour ambulatory arrhythmias,heart rate variability,ST-segment deviation,and blood pressure(BP)in Beijing,China,2014-2016.Generalized additive mixed models coupled with distributed lag nonlinear models were constructed to evaluate the associations and potential interlinks between O3 exposure and outcome measurements.Results:During the study period,24-hour average concentrations of ambient O3 were 47.4 μg/m3(ranging from 1.0 to 165.9 μg/m3).Increased risks of premature ventricular contraction and ventricular tachycardia were associated with interquartile range increases in O3 exposure during the last 5 days before each participant's clinic visit,with relative risks of 2.14(95%confidence interval[CI]:1.95 to 2.32)and 5.47(95%CI:3.51 to 7.43),respectively.Mediation analyses further showed that sympathetic activation,parasympathetic inhibition,and elevated BP levels,as well as heightened risks of ST-segment depression could mediate up to 47.74%of the risks of arrhythmias attributable to O3 exposure.Conclusion:Our results suggest that short-term exposure to ambient O3 could prompt the genesis of arrhythmias partially through worsening autonomic function and myocardial burden.
10.An extended analysis of cardiovascular benefits of indoor air filtration intervention among elderly:a randomized crossover trial(Beijing indoor air purifier study,BIAPSY)
Chen JIE ; Wang TONG ; Xu HONGBING ; Zhu YUTONG ; Du YIPENG ; Liu BEIBEI ; Zhao QIAN ; Zhang YI ; Liu LINGYAN ; Yuan NINGMAN ; Fang JIAKUN ; Xie YUNFEI ; Liu SHUO ; Wu RONGSHAN ; Shao DANQING ; Song XIAOMING ; He BEI ; Brunekreef BERT ; Huang WEI
Global Health Journal 2022;6(1):30-34
Objective:Evidence on potential cardiovascular benefits of personal-level intervention among the elderly exposed to high levels of particulate matter(PM)remains limited.We aimed to assess improvements in surrogate markers of cardiovascular injury in vulnerable populations at risks by using indoor air filtration units.Methods:We conducted a randomized crossover trial for 2 separate 2-week air filtration interventions in 20 households of patients with stable chronic obstructive pulmonary disease and their partners in the winter of 2013,with concurrent measurements of indoor PM.The changes in biomarkers indicative of cardiac injury,atherosclerosis progression and systemic inflammation following intervention were evaluated using linear mixed-effect models.Results:In the analysis,average levels of indoor PM with aerodynamic diameters<2.5 μm(PM2.5)decreased significantly by 59.2%(from 59.6 to 24.3 μg/m3,P<0.001)during the active air filtration.The reduction was accompanied by improvements in levels of high-sensitivity cardiac troponin I by-84.6%(95%confidence interval[CI]:-90.7 to-78.6),growth differentiation factor-15 by-48.1%(95%CI:-31.2 to-25.6),osteoprotegerin by-65.4%(95%CI:-56.5 to-18.7),interleukin-4 by-46.6%(95%CI:-62.3 to-31.0)and myeloperoxidase by-60.3%(95%CI:-83.7 to-3.0),respectively.Conclusion:Indoor air filtration intervention may provide potential cardiovascular benefits in vulnerable popu-lations at risks.


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