1.27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression:A key target potentially linking zearalenone and cancer
Ruan HAONAN ; Zhang JING ; Wang YUNYUN ; Huang YING ; Wu JIASHUO ; He CHUNJIAO ; Ke TONGWEI ; Luo JIAOYANG ; Yang MEIHUA
Journal of Pharmaceutical Analysis 2024;14(3):371-388
Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosup-pression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P<0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P<0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P<0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These find-ings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.
2.Inhibition of FoxO1 exerts a protective effect on diabetic cardiomyopathy rats by regulating JAK/STAT3 signaling pathway
Huilin LUO ; Zhilin WU ; Yunyun YANG
Chinese Journal of Diabetes 2024;32(9):689-694
Objective To investigate the impact of forkhead box O1(FoxO1)on oxidative stress andcardiomyocyte apoptosis in diabetic cardiomyopathy(DCM)rats through Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)pathway.Methods A total of 60 rats were divided into normal control group(NC),model group(Mod),FoxO1 agonist group(Res),FoxO1 inhibitor group(AS1842856)and FoxO1 inhibitor+AG490 group(AS1842856+AG490),with 12 rats in each group.DCM models were established in all groups except NC group.After successful modeling,they were given drugs,and the levels of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-PX)were tested.HE and Masson staining were used to detect the pathological damage of myocardial tissue.TUNEL staining was used to observe myocardial apoptosis.Western blot was used to detect FoxO1,Bim,Bcl-2 related X protein(Bax),p-JAK1,p-JAK2,p-STAT3,JAK1,JAK2 and STAT3 proteins.Results Compared with NC group,the expressions of FBG,MDA,cardiomyocyte apoptosis rate,FoxO1 protein,Bax protein and Bim protein were increased(P<0.05),while the expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 were increased in Mod group(P<0.05).Compared with Mod group,FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein increased(P<0.05),while the expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 decreased in Res group(P<0.05).The expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 increased(P<0.05),while FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein decreased in AS1842856 group(P<0.05).Compared with AS1842856 group,FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein increased(P<0.05),and HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2,p-STAT3/STAT3 decreasedin AS1842856+AG490 group(P<0.05).Conclusions Inhibition of FoxO1 may exert a protective effect on DCM rats by activating the JAK2/STAT3 pathway.
3.Measurement of 239Pu in fecal samples based on inductively coupled plasma-mass spectrometry
Guowen ZHENG ; Chuangao WANG ; Yunyun YIN ; Zhiping LUO ; Hongchao PANG
Chinese Journal of Radiological Health 2023;32(6):632-635
Objective To establish a method for measurement of 239Pu in fecal samples based on inductively coupled plasma-mass spectrometry (ICP-MS), and to provide a novel method for assessing the internal exposure of workers. Methods Fecal samples were collected from workers and labeled. The samples were pretreated with carbonization ashing and microwave digestion devices, purified on TEVA resin, and measured using ICP-MS. Results The detection limit of 239Pu in fecal samples based on ICP-MS was 1.91 × 10−4 Bq. Conclusion In the routine monitoring of class S substances characterized by a 5 μm aerodynamic diameter during 12 months, the committed effective dose corresponding to the detection limit is 0.17 mSv. This value meets the requirements of relevant national standards and ICP-MS can be used as a novel means for accurate evaluation of internal exposure for workers.
4.Study on the fingerprint of total saponins from Mussaenda pubescens and the spectrum-effect relationship of its hepatoprotective activity
Ying ZHANG ; Jinrong LUO ; Yunyun ZHANG ; Feng CHEN ; Fei HE ; Jia LI
China Pharmacy 2023;34(22):2715-2720
OBJECTIVE To establish the fingerprint of total saponins from Mussaenda pubescens, and to study the spectrum- effect relationship of its hepatoprotective activity. METHODS Ten batches of total saponins from M. pubescens from different origins were prepared using 75% ethanol as solvent. High-performance liquid chromatography (HPLC) and the Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints (2012 edition) were used to draw the fingerprints of 10 batches of total saponins from M. pubescens. The similarity evaluation and identification of common peaks were conducted. The same HPLC method was adopted to determine the contents of five triterpenoid saponins (mussaendoside H, mussaendoside U, mussaglaoside C, mussaendoside G and mussaendoside O). The hepatoprotective effect of total saponins from M. pubescens was investigated by establishing carbon tetrachloride-induced acute liver injury model mice, and the spectrum-effect relationship was studied by using grey correlation analysis. RESULTS There were 11 common peaks in 10 batches of total saponins from M. pubescens, 5 of which were identified, i.e. mussaendoside H (peak 3), mussaendoside U (peak 7), mussaglaoside C (peak 8), mussaendoside G (peak 9) and mussaendoside O (peak 11); the similarities of 10 batches of samples ranged 0.940- 0.991. Average contents of mussaendoside H, mussaendoside U, mussaglaoside C, mussaendoside G, mussaendoside O were 0.01- 0.05, 0.10-0.21, 0.10-0.18, 0.03-0.08, 0.20-0.40 mg/g, respectively. Ten batches of total saponins from M. pubescens could generally reduce the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in liver tissue of model mice (P<0.05 or P<0.01). The E-mail:13878195336@139.com correlation between the common peak areas and the contents of ALT, AST, TNF-α, IL-6 and IL-1β were 0.602-0.757, 0.585-0.833, 0.593-0.795, 0.618-0.820, 0.607-0.804, respectively; the peaks with high correlation were peaks 11, 9 and 8 in order. CONCLUSIONS Ten batches of total saponins from M. pubescens have similar components, and the average contents of mussaendoside H, mussaendoside U, mussaglaoside C, mussaendoside G and mussaendoside O are different. The batches of samples have a certain degree of hepatoprotective effect; mussaendoside O, mussaendoside G and mussaglaoside C may be its main active components.
5.A case of congenital systemic lipodystrophy with exfoliated xanthoma caused by AGPAT2 gene mutation
Yunyun LUO ; Liyuan ZHANG ; Xinyi WANG ; He LIU ; Hanze DU ; Hui PAN
Basic & Clinical Medicine 2023;43(12):1852-1856
Objective To analyze the clinical characteristics and genotype of a patient with congenital systemic lip-odystrophy(CGL)type 1 associated with exudative xanthoma caused by AGPAT2 gene mutation,and to provide ev-idence for clinical and genetic diagnosis of the disease.Methods Clinical data of the patient such as medical histo-ry,physical examination and laboratory examination were collected.Peripheral venous blood was collected for whole exome sequencing analysis and Sanger sequencing verification,and treatment was provided to patients according to the changes of condition.Results The clinical manifestations of the patient were subcutaneous fat reduction,fatty liver,spleen enlargement,kidney enlargement,high blood sugar and lipids,severe insulin resistance,scattered yellow rash on limbs,which was confirmed as xanthoma.The results of whole exon sequencing showed that the AGPAT2 gene of the patient had a heterozygous nonsense mutation of c.202C>T:p.R68?and c.646A>T:p.K216?,and the former was the pathogenic mutation site.Follow-up therapy covers improvement of lifestyle,low-fat diet and regular exercise.The rashes subsided after active lipid-lowering therapy.Conclusions Apart from typical lipody-strophy,the patient was accompanied by exanthemous xanthoma.No CGL1 patient with exanthemous xanthoma has been reported in the domestic literature database up to now,and the genetic test results showed that there was a c.202C>T heterozygous mutation of AGPAT2 gene.This gene site has not been reported in the literature,and its functional verification needs to be further studied.
6.Exploration of 241Am measurement in fecal samples
Weina SONG ; Yunyun YIN ; Aiyun LI ; Chuangao WANG ; Zhiping LUO ; Hongchao PANG
Chinese Journal of Radiological Health 2022;31(5):542-547
Objective To preliminarily study and establish a method for measurement of the transuranic nuclide 241Am in fecal samples, and to provide technical support for internal radiation monitoring of staff. Methods Fecal samples were collected with a self-made stool sampler and treated with a self-made carbonization and ashing furnace. DGA resin was used to separate and purify 241Am from fecal samples. With 243Am as the tracer, the orthogonal method was used for condition optimization. Results The optimum conditions for separation and purification were: the acidity of HNO3 added into the column, 6 mol/L; column flow rate, 0.6 mL/min; and the volume of analytical solution,12 mL. The method based on inductively coupled plasma mass spectrometry showed a detection limit of 9.79×10−4 Bq for 241Am in fecal samples, which was satisfactory and feasible. Conclusion This method fills the vacancy of 241Am measurement in fecal samples to some extent, which is of practical significance for internal radiation monitoring and protection for analysts.
7.99Tc m-DTPA SPECT/CT imaging in the diagnosis of cerebrospinal fluid leakage
Yunyun ZHU ; Chentian SHEN ; Zhenkui SUN ; Hongjun SONG ; Yang WANG ; Ruisen ZHU ; Weitian ZHANG ; Quanyong LUO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(10):617-621
Objective:To investigate the diagnostic efficacy and clinical application value of 99Tc m-diethylene triamine pentaacetic acid (DTPA) SPECT/CT imaging in cerebrospinal fluid leakage (CSFL). Methods:A total of 23 patients (11 males, 12 females; age (44.2±15.1) years) who underwent endoscopic repair surgery for suspected CSFL in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital between April 2018 and January 2020 were retrospectively reviewed. All patients performed 99Tc m-DTPA SPECT/CT imaging, paranasal sinus high resolution CT (HRCT) and MRI before surgery. The diagnostic efficacies of 3 imaging techniques were calculated according to the result of surgery regarded as the golden standard. χ2 test was used to compare the qualitative and localized diagnostic efficacies of 3 imaging techniques for CSFL. Results:Of 23 patients, 21 were finally confirmed with CSFL and 24 leak locations were identified according to the results of surgery; the other 2 patients had no obvious CSFL and no leak location was found during the operation. The sensitivity and accuracy of 99Tc m-DTPA SPECT/CT, MRI and HRCT for the diagnosis of CSFL were 100%(21/21) and 95.7%(22/23), 85.7%(18/21) and 82.6%(19/23), 76.2%(16/21) and 69.6%(16/23), respectively. The accuracy of 99Tc m-DTPA SPECT/CT, MRI and HRCT for the diagnosis of leak location was 79.2%(19/24), 50.0%(12/24) and 45.8%(11/24), respectively. There was no statistically significant difference of diagnostic efficacies for CSFL among 3 imaging techniques ( χ2 values: 0.451-3.453, all P>0.05). For leak location, the diagnostic efficacy of 99Tc m-DTPA SPECT/CT was significantly better than that of MRI and HRCT ( χ2 values: 4.463, 5.689, both P<0.05). Conclusion:99Tc m-DTPA SPECT/CT imaging shows an excellent diagnosis efficacy not only for CSFL but also for leak location, which is helpful for guiding surgery.
8.Construction of community remote rehabilitation networks for stroke patients based on Internet of things technology
Xiaoguang LIU ; Haoyu WANG ; Chunhui QIN ; Haiyan GU ; Yuhua ZHAN ; Ping GAO ; Liang TAO ; Kun WEI ; Yanfen PANG ; Mingfei ZOU ; Yunyun LUO
Chinese Journal of Hospital Administration 2021;37(7):565-569
The development of information technology in the medical industry is accelerating the construction of 3-level rehabilitation networks centering on community-based rehabilitation, which is based on the Internet and in combination with the Internet of things(IOT). A municipal rehabilitation hospital cooperated with the health centers of sub-district communities in the city to build a remote rehabilitation network based on IOT technology, for rehabilitation training of community stroke patients. The two sides worked out a cooperation scheme on project management, designed and built a remote community rehabilitation management model. Under the remote monitoring and equipment data IOT, the medical team of the municipal rehabilitation hospital could formulate the therapeutic plan according to the immediately obtained relevant functional evaluation data, and the medical team of the community health service center was responsible for the implementation of the plan. Fifty-three patients in the experimental group received the training of remote lower limb intelligent feedback system based on IOT together with routine rehabilitation training. After 8 weeks of treatment, the functional evaluation data of the two groups were improved in varying degrees( P< 0.05), but the improvement of the experimental group was significantly better than that of the control group( P < 0.05). Remote rehabilitation under the construction path of remote rehabilitation network based on IOT technology could significantly promote the improvement of post-functional rehabilitation of community stroke patients. This study can provide reference for the construction of three-level remote rehabilitation networks based on IOT and the implementation of home-based remote rehabilitation therapy in the future.
9.Development and evaluation of a machine learning prediction model for large for gestational age
Xi BAI ; Yunyun LUO ; Zhibo ZHOU ; Mingliang SU ; Liuqing YANG ; Shi CHEN ; Hongbo YANG ; Huijuan ZHU ; Hui PAN
Chinese Journal of Epidemiology 2021;42(12):2143-2148
Objective:To develop and validate a useful predictive model for large gestational age (LGA) in pregnancy using a machine learning (ML) algorithm and compare its performance with the traditional logistic regression model.Methods:Data were obtained from the National Free Preconception Health Examination Project in China, carried out in 220 counties of 31 provinces from 2010 to 2012, covering all rural couples with a planned pregnancy. This study included all teams of childbearing age who delivered newborns within 24-42 weeks of gestational age and their newborns. Ten different ML algorithms were used to establish LGA prediction models, and the prediction performance of these models was evaluated.Results:A total of 104 936 newborns were included, including 54 856 boys (52.3%) and 50 080 girls (47.7%). The incidence of LGA was 11.7% (12 279). The imbalance between the two groups was addressed by the under- sampling technique, after which the overall performance of the ML models was significantly improved. The CatBoost model achieved the highest area under the receiver-operating-characteristic curve (AUC) value of 0.932. The logistic regression model had the worst performance, with an AUC of 0.555.Conclusions:In predicting the risk for LGA in pregnancy, the ML algorithms outperform the traditional logistic regression method. Compared to other ML algorithms, CatBoost could improve the performance, and it deserves further investigation.
10.Comparison of Corticosteroids by 3 Approaches to the Treatment of Chronic Rhinosinusitis With Nasal Polyps
Yunyun ZHANG ; Hongfei LOU ; Yang WANG ; Ying LI ; Luo ZHANG ; Chengshuo WANG
Allergy, Asthma & Immunology Research 2019;11(4):482-497
PURPOSE: Corticosteroids are regarded as the mainstay of medical treatment of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). To date, a head-to-head comparison of the efficacy and safety of glucocorticoid preparations administered via different routes for the treatment of chronic rhinosinusitis with nasal polyps has not been reported. To compare the efficacy and safety of steroids administered via the oral, intranasal spray and transnasal nebulization routes in the management of ECRSwNP over a short course. METHODS: Overall, 91 patients with ECRSwNP were recruited prospectively and randomized to receive either oral methylprednisolone, budesonide inhalation suspension (BIS) via transnasal nebulization, or budesonide nasal spray (BNS) for 2 weeks. Nasal symptoms and polyp sizes were assessed before and after the treatment. Similarly, nasal polyp samples were evaluated for immunological and tissue remodeling markers. Serum cortisol levels were assessed as a safety outcome. RESULTS: Oral methylprednisolone and BIS decreased symptoms and polyp sizes to a significantly greater extent from baseline (P < 0.05) than BNS. Similarly, BIS and oral methylprednisolone significantly reduced eosinophils, T helper 2 cells, eosinophil cationic protein, interleukin (IL)-5, and expression of matrix metalloproteinases 2 and 9, and significantly increased type 1 regulatory T cells, IL-10, transforming growth factor-β, and tissue inhibitor of metalloproteinases 1 and 2 in nasal polyps to a greater extent than BNS. Post-treatment serum cortisol levels were significantly decreased by oral methylprednisolone compared to BIS or BNS, which did not significantly alter the cortisol levels. CONCLUSIONS: A short course of BIS transnasal nebulization is more efficacious compared to BNS in the management of ECRSwNP and is safer than oral methylprednisolone with respect to hypothalamic-pituitary-adrenal axis function.
Adrenal Cortex Hormones
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Budesonide
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Eosinophil Cationic Protein
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Eosinophils
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Glucocorticoids
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Humans
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Hydrocortisone
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Inhalation
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Interleukin-10
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Interleukins
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Matrix Metalloproteinases
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Methylprednisolone
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Nasal Polyps
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Polyps
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Prospective Studies
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Steroids
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T-Lymphocytes, Regulatory
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Tissue Inhibitor of Metalloproteinases


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