1. Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats
Rui-Ying TIAN ; Wen-Xin MA ; Zi-Yu LIU ; Hui-Ming MA ; Sha-Sha XING ; Na HU ; Chang LIU ; Biao MA ; Jia-Yang LI ; Hu-Jun LIU ; Chang-Cai BAI ; Dong-Mei CHEN
Chinese Pharmacological Bulletin 2024;40(3):490-498
Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.
2.Effects of PM2.5 sub-chronic exposure on liver metabolomics in mice
Liu YANG ; Siqi DOU ; Xinyuan LI ; Shuo WEN ; Kun PAN ; Biao WU ; Jinzhuo ZHAO ; Jianjun XU ; Peng LYU
Journal of Environmental and Occupational Medicine 2024;41(2):207-213
Background Atmospheric fine particulate matter (PM2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM2.5 exposure.
3.Identification of potential pathogenic genes of intestinal metaplasia based on transcriptomic sequencing and bioinformatics analysis
Bei PEI ; Yi ZHANG ; Siyuan WEI ; Yu MEI ; Biao SONG ; Gang DONG ; Ziang WEN ; Xuejun LI
Journal of Southern Medical University 2024;44(5):941-949
Objective To explore the potential pathogenic genes of intestinal metaplasia.Methods Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January,2022 to June,2022,and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study.All the participants underwent gastroscopy and pathological examination,and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes(DEGs).The biological functions of the DEGs were analyzed using bioinformatics analysis,and qRT-PCR was used to validate the results.Results Transcriptomic sequencing identified a total of 1373 DEGs,including 827 upregulated and 546 downregulated ones.The top 6 upregulated genes(AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2),ranked based on their significance and average expression level,were selected for validation,and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia(P<0.05).Conclusion AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2 participate in the occurrence and development of intestinal metaplasia,and may serve as potential biomarkers for diagnosing intestinal metaplasia.
4.Transcutaneous Electrical Acupoint Stimulation Promotes PGC-1α Mediated Mitochondrial Biogenesis and Antioxidant Stress to Protect Cognitive Function in Vascular Dementia Rats
Ji-Liang KANG ; Ke HU ; Jun-Yue LU ; Zi-Wei HU ; Biao-Ping XU ; Xiao-Mao LI ; Jun-Jie ZHOU ; Yu JIN ; Min TANG ; Rong XU ; You-Liang WEN
Progress in Biochemistry and Biophysics 2024;51(5):1191-1202
ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.
5.Identification of potential pathogenic genes of intestinal metaplasia based on transcriptomic sequencing and bioinformatics analysis
Bei PEI ; Yi ZHANG ; Siyuan WEI ; Yu MEI ; Biao SONG ; Gang DONG ; Ziang WEN ; Xuejun LI
Journal of Southern Medical University 2024;44(5):941-949
Objective To explore the potential pathogenic genes of intestinal metaplasia.Methods Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January,2022 to June,2022,and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study.All the participants underwent gastroscopy and pathological examination,and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes(DEGs).The biological functions of the DEGs were analyzed using bioinformatics analysis,and qRT-PCR was used to validate the results.Results Transcriptomic sequencing identified a total of 1373 DEGs,including 827 upregulated and 546 downregulated ones.The top 6 upregulated genes(AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2),ranked based on their significance and average expression level,were selected for validation,and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia(P<0.05).Conclusion AGMAT,CCL25,FABP1,CDX1,SPINK4,and MUC2 participate in the occurrence and development of intestinal metaplasia,and may serve as potential biomarkers for diagnosing intestinal metaplasia.
6.Research on face mask recognition based on YOLOv5 lightweight network
Liang WEN ; Jiang WANG ; Guo-Biao LIANG ; Zhen-Ni LI
Chinese Medical Equipment Journal 2024;45(9):7-13
Objective To propose a YOLOv5 lightweight network-based face mask recognition method to solve the problems due to limited storage and computation resources of edge and mobile devices.Methods A YOLOv5 model composed of a backbone network(Backbone),a neck module(Neck)and a head module(Head)was selected as the base framework.Firstly,the Backbone part was modified and replaced using the ShuffleNetv2 lightweight network;secondly,a Ghost module and a C3_S module were introduced in the Neck part;finally,a Shuffle_Yolo_GS_CBAM model was formed by incorporating a convolutional block attention module(CBAM)to improve the detection accuracy.The model was trained and verified with the AIZOO dataset,which was evaluated for face mask recognition by mean average precision(mAP),frames per second(FPS),giga floating-point operations per second(GFLOPS)and parameters.Results The model proposed recognized face masks with the mAP being 89.5%,FPS being 158.7 frames/s,parameters being 2.38 M and and GFLOPS being 4.5 GFLOPS,which had the detection speed enhanced by 39.7%,parameters decreased by 67.3%and operations reduced by73.8%when compared with the YOLOv5s model.Conclusion The method proposed behaves well in increasing detection speed,decreasing parameters and operations and ensuring detection precision,and thus is worthy promoting for face mask recognition on edge and mobile devices.[Chinese Medical Equipment Journal,2024,45(9):7-13]
7.Clinical Analysis of CD4+CD8-T-Cell Large Granular Lymphocytic Leukemia
Xiang-Xiang CHANG ; Shang-Biao SUN ; Yu-Wen LI ; Miao WANG ; Yan-Qing ZHU
Journal of Experimental Hematology 2024;32(5):1388-1393
Objective:To investigate the clinical characteristics and treatment of patients with CD4+CD8-T-cell large granular lymphocytic leukemia(T-LGLL).Methods:The clinical manifestations,diagnosis and treatment of 1 case of CD4+CD8-T-LGLL patient were reported,and relevant literatures were reviewed.Results:The patient was a 70-year-old woman with slow clinical progress,mainly manifested by thrombocytopenia and myelodysplasia.The blood smear was mainly composed of large granular lymphocytes.Immunotyping and T-cell receptor gene rearrangement analysis showed that it was in line with T-LGLL.Partial remission(PR)was achieved through the treatment of cyclophosphamide(50 mg/d)combined with prednisone(gradually reduced and stopped later).Conclusion:CD4+CD8-T-LGLL is very rare in clinical practice,and its clinical manifestations are different from those of CD4-CD8+T-LGLL.
8.The effects of different dose calculation grid size by Monaco planning system on the dosimetry of T 4 nasopharyngeal carcinoma
Jinzhi LI ; Biao ZHAO ; Xiaobo WEN ; Ming ZHANG ; Meifang YUAN ; Mengzhen SUN ; Qin PU ; Yi YANG
Journal of International Oncology 2023;50(11):641-649
Objective:To analyze the effects of different dose calculation grid size of Monaco system on the physical and biological dosimetry of target area and organ at risk (OAR) in T 4 nasopharyngeal carcinoma. Methods:A total of 18 patients with stage T 4 nasopharyngeal carcinoma who received radiotherapy in the Department of Radiotherapy of Yunnan Cancer Hospital from October 2020 to April 2022 were selected to complete the delineation of target areas and OAR in the Monaco 5.11.03 system, and the volumetric intensity modulated arc therapy (VMAT) plan was developed on the 3 mm grid with the optimization mode of target area priority. The 3 mm grid group plan was replicated without changing any other parameters, and the physical plan was re-established on the 1, 2, 4 and 5 mm grids, and then the five plans were normalized to the prescription dose to cover 95% of the target volume. The planning time, D 2%, D 50%, D 98%, conformity index (CI), homogeneity index (HI), gradient index (GI), tumor control probability (TCP), D 2% and D mean of important OAR around the target area were calculated and statistically analyzed. Results:Planning primary tumor gross target volume (PGTVp) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.94±0.66), (75.98±0.76), (75.56±0.67), (75.67±0.73) and (75.94±0.85) Gy, respectively, with a statistically significant difference ( F=9.86, P<0.001). The CI of 1, 2, 3, 4 and 5 mm groups were 0.75±0.05, 0.78±0.04, 0.78±0.05, 0.79±0.04 and 0.78±0.04, respectively, with a statistically significant difference ( F=2.61, P=0.041). There were statistically significant differences in D 50%, D 98%, HI, equivalent uniform dose (EUD) and tumor control probability (TCP) among the groups ( H=17.14, P=0.002; F=9.35, P<0.001; H=25.43, P<0.001; F=5.85, P<0.001; H=17.65, P=0.001). There was no statistically significant difference in GI among the groups ( P>0.05). Pairwise comparison showed that D 2% in 2, 3, 4, 5 mm groups compared with 1 mm group, D 50% in 5 mm group compared with 2, 3 mm groups, D 98% in 4 mm group compared with 1, 2 mm groups, D 98% in 5 mm group compared with 1, 2, 3 mm groups, CI in 5 mm group compared with 1 mm group, HI in 2, 3, 4, 5 mm groups compared with 1 mm group, EUD in 3 mm group was compared with 1 mm group, EUD in 5 mm group compared with 2, 3 mm groups, TCP in 3 mm group compared with 1 mm group, and TCP in 5 mm group compared with 3 mm group, there were statistically significant differences (all P<0.05). Planning nodal gross target volume (PGTVn) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.36±0.59), (75.36±0.62), (75.04±0.68), (75.25±0.72) and (75.39±0.77) Gy, respectively, with a statistically significant difference ( F=10.32, P<0.001). The HI of 1, 2, 3, 4 and 5 mm groups were 1.08 (1.08, 1.08), 1.07 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.07), 1.06 (1.06, 1.08), respectively, with a statistically significant difference ( H=22.00, P<0.001) ; There were statistically significant differences in D 50%, D 98% and EUD among the groups ( H=11.79, P=0.019; H=20.49, P<0.001; F=12.14, P=0.016). Pairwise comparison showed that there were statistically significant differences in D 2% between 2, 3, 4, 5 mm groups and 1 mm group, D 98% between 4 mm group and 1 mm group, D 98% between 5 mm group and 1, 2 mm groups, HI between 2, 3, 4 mm groups and 1 mm group, and EUD between 3 mm group and 1 mm group (all P<0.05). Planning primary tumor clinical target volume 1 (PCTVp1) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (76.59±0.63), (75.64±0.65), (75.64±0.98), (75.41±0.70) and (75.71±0.84) Gy, respectively, with a statistically significant difference ( F=9.53, P<0.001). The D 50% of 1, 2, 3, 4, 5 mm groups were (72.09±0.34), (71.85±0.39), (71.82±0.45), (72.04±0.56), (72.43±0.66) Gy, respectively, with a statistically significant difference ( F=4.20, P=0.019). There was no statistically significant difference in the other indexes among the groups (all P>0.05). Pairwise comparison showed that there were statistically significant differences in D 2% between 2, 3, 4, 5 mm groups and 1 mm group, and in D 50% between 2, 3 mm groups and 1 mm group (all P<0.05). Planning nodal clinical target volume 1 (PCTVn1) : There were no statistically significant differences in all indexes among the groups (all P>0.05). Planning clinical target volume 2 (PCTV2) : The D 2% of 1, 2, 3, 4 and 5 mm groups were (75.57±0.50), (74.87±0.67), (74.51±0.51), (74.61±0.63) and (75.00±0.74) Gy, respectively, with a statistically significant difference ( F=8.27, P<0.001). Pairwise comparison showed that the D 2% of the 2, 3, 4 mm groups were significantly different from that of the 1 mm group (all P<0.05). The calculation time of physical plan in 1, 2, 4 and 5 mm groups was 987.00 (848.00, 1 091.00), 120.50 (99.75, 134.00), 26.00 (24.00, 34.25) and 21.50 (18.75, 34.75) s, respectively, with a statistically significant difference ( H=61.62, P<0.001). Pairwise comparison showed that there were statistically significant differences in the calculation time between 4 mm group and 1, 2 mm groups, 5 mm group and 1, 2 mm groups (all P<0.05). There was no statistically significant difference in the dosimetric parameters of OAR around the target area among the groups (all P>0.05) . Conclusion:The physical dose and biological dose of the important OAR around the target area and the target area change with the change of dose calculation grid size when formulating the physical plan of radiotherapy for T 4 nasopharyngeal carcinoma. Considering the quality of the physical plan and the calculation time, when the Monaco system formulates the VMAT plan for T 4 nasopharyngeal carcinoma patients, the plan can be optimized on the 3 mm computing grid and copied to the 1 mm computing grid for recalculation.
9.Application research and design strategy on smart responsive mesoporous silica anti-tumor nanodelivery systems
Biao LI ; Ying-chong CHEN ; Bao-de SHEN ; Wen-ting WU ; Qin ZHENG ; Peng-fei YUE
Acta Pharmaceutica Sinica 2023;58(3):494-505
Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.
10.Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial.
Yu-Jie WU ; Bo DENG ; Si-Bo WANG ; Rui QIAO ; Xi-Wen ZHANG ; Yuan LU ; Li WANG ; Shun-Zhong GU ; Yu-Qing ZHANG ; Kai-Qiao LI ; Zong-Liang YU ; Li-Xing WU ; Sheng-Biao ZHAO ; Shuang-Lin ZHOU ; Yang YANG ; Lian-Sheng WANG
Chinese journal of integrative medicine 2023;29(12):1059-1065
BACKGROUND:
Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.
OBJECTIVE:
This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.
METHODS:
This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment.
DISCUSSION
This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans
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ST Elevation Myocardial Infarction/therapy*
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Stroke Volume
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Ventricular Remodeling
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Prospective Studies
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Microcirculation
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Ventricular Function, Left
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Myocardial Infarction/etiology*
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Treatment Outcome
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Percutaneous Coronary Intervention/adverse effects*
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Heart Failure/drug therapy*
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Drugs, Chinese Herbal/therapeutic use*
;
Randomized Controlled Trials as Topic
;
Multicenter Studies as Topic

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