1.Excavation and evaluation of tocilizumab and infliximab for adverse drug event signals among children
Yue TAN ; Ning-Ning GE ; Jing PENG ; Wen-Shuang QIU ; Xin ZHANG ; Lan-Fang LI
The Chinese Journal of Clinical Pharmacology 2024;40(5):732-736
Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.
2.Characteristics of foot development in children under 3 years old in Xi′an City
Shuang FENG ; Zhaohui WANG ; Dong WANG ; Jiaojiao REN ; Hongjuan LI ; Shasha GE
Chinese Journal of Child Health Care 2024;32(4):440-444
【Objective】 To measure and analyze foot development indicators of children under 3 years old, in order to provide basis for the correct clinical assessment of children foot development. 【Methods】 A total of 5 894 children under 3 years old who took physical examination in the Child Health Care Department of Xi′an People′s Hospital from August 2022 to March 2023 were randomly selected. Foot length, foot width, the ratio of foot width to length and arch index were measured by image processing system, and were compared among different age groups and sex groups. 【Results】 1) Foot length, foot width and arch index of children under 3 years old increased significantly with age, while the ratio of foot width to length decreased significantly with age(F=1 345.23, 396.21,184.65, 287.03, P<0.05). 2) There was no statistical significance in foot length, foot width and arch index between left and right foot of children under 3 years old(P>0.05). 3) Foot length and foot width of boys were greater than those of girls in all age groups, and the difference was statistically significant(t
3.Prediction of EGFR mutation status in lung adenocarcinoma based on standardized enhanced CT radiomics nomogram
Xun WANG ; Shuang GE ; Huizhen XI ; Jun MA ; Yaru LIU ; Shucheng YE ; Junli MA
Chinese Journal of Radiological Medicine and Protection 2024;44(3):194-201
Objective:To investigate the value of radiomics nomogram based on standardized pre-treatment chest enhanced CT in predicting the mutation status of epidermal growth factor receptor (EGFR) for patients with lung adenocarcinoma.Methods:A retrospective analysis was conducted on pre-treatment chest enhanced CT images and clinical data of 262 patients from the affiliated hospital of Jining Medical University with pathologically proven primary lung adenocarcinoma who received EGFR gene testing, including EGFR wild type ( n=122) and mutant type ( n=140). The patients were divided into training group ( n=183) and testing group ( n=79) according to a ratio of 7∶3 by stratified sampling method. Standardized pre-processed the images, delineated the ROI and extracted the radiomics features. Least absolute shrinkage and selection operator (LASSO) algorithm was used to reduce the dimension and select key features. The standardized radiomics model, clinical model and the combined model were established by Logistic Regression (LR) machine learning method. Calculated the Rad-score and drew the nomogram. ROC curve and Delong were used to evaluate and compare the predictive performance of different models. Results:23 standardized enhanced CT radiomics features and 4 clinical features were selected. The predictive performance of standardized radiomics model was better than that of non-standardized radiomics model [area under curve (AUC): 0.863 vs. 0.805, t=2.19, P<0.05]. The AUCs of the combined model and standardized radiomics model were higher than that of the clinical model (training group: 0.885, 0.863 vs. 0.774, t=3.57, 2.17, P<0.05; testing group: 0.873, 0.829 vs. 0.763, t=2.19, 2.02, P<0.05). The radiomics nomogram was built based on Rad-score, age, sex, smoking history and BMI. Conclusions:The combined model and standardized radiomics model could effectively predict the mutation status of EGFR gene in lung adenocarcinoma patients before treatment, providing valuable clinical insights.
4.Efficacy and safety analysis of tislelizumab in the treatment of advanced gastric cancer
Ge SONG ; Yuqian GAO ; Shuang LUO ; Xiaoling TIAN ; Yunqi HUA
Chinese Journal of Postgraduates of Medicine 2024;47(9):846-851
Objective:To analyze the efficacy and safety of tislelizumab in the treatment of advanced gastric cancer.Methods:The clinical data of 54 patients with advanced gastric cancer in Baotou Cancer Hospital from July 2022 to December 2023 were retrospectively analyzed. Among them, 27 patients were treated with chemotherapy (control group), and 27 patients were treated with tislelizumab combined with chemotherapy (combination group). The efficacy was evaluated after 2 cycles. The patients were followed up until March 2024, and the survival status was evaluated by progression-free survival (PFS) and duration of remission (DOR). The adverse reactions were recorded. Kaplan-Meier survival curve was drawn, and the compared used log rank test. Binary Logistic regression was used to analyze the independent risk factors of efficacy in patients with advanced gastric cancer.Results:The effective rate and disease control rate in combined group were significantly higher than those in control group: 29.6% (8/27) vs. 7.4% (2/27) and 85.2% (23/27) vs. 59.3% (16/27), and there were statistical differences ( χ2 = 4.42 and 4.52, P<0.05). Kaplan-Meier survival curve analysis result showed that the median PFS and DOR in combination group were significantly longer than those in control group (9.9 months vs. 7.2 months and 8.7 months vs. 6.4 months), and there were statistical differences (log-rank χ2 = 6.58 and 8.47, P<0.05). Among the 54 patients, 10 cases (18.5%) were effective, and 44 cases (81.5%) were ineffective. The efficacy was related to the number of organ metastase, prealbumin and Helicobacter pylori infection rate, and there were statistical differences ( P<0.05). Binary Logistic regression analysis result showed that the number of organ metastase >1, prealbumin <160 mg/L and Helicobacter pylori infection were independent risk factors of efficacy in patients with advanced gastric cancer ( OR = 0.089, 8.418 and 0.153; 95% CI 0.012 to 0.661, 1.255 to 56.449 and 0.025 to 0.944; P<0.05). There was no statistical difference in the incidence of adverse reactions between two groups ( P>0.05). Conclusions:The tislelizumab combined with chemotherapy in patients with advanced gastric cancer can improve the efficacy and prolong the survival without increasing the incidence of adverse reactions.
5.Expression and clinical significance of peroxisome proliferator-activated receptors in endometriosis
Qin LUO ; Min TIAN ; Shuang GAO ; Jie HUANG ; Ge DIAO ; Li LI ; Jian HAN ; Jianxin GUO
Chongqing Medicine 2024;53(13):1952-1958
Objective To analyze the expression levels of the three different subtypes of peroxisome proliferator-activated receptors(PPARs),including PPAR-α,PPAR-β and PPAR-γ,in the ectopic lesion tis-sues of the patients with endometriosis(EMs)in order to provide new methods for this disease diagnosis.Methods The ectopic endometrial tissue samples from 30 patients with EMs treated by laparoscopic surgery in this hospital from April to December 2021 were selected as the experimental group,and the ovarian lesion tissue samples from 30 patients with mature cystic teratoma of the ovary(MCTO)during the same period treated by laparoscopic surgery were selected as the control group.The expression levels of PPAR-α,PPAR-βand PPAR-γ in lesion tissues were detected by using immunohistochemistry,and their expression differences between the experimental group and control group were analyzed.The receiver operating characteristic(ROC)curve was utilized to evaluate the diagnostic value of the ratios of PPAR-α/PPAR-β,PPAR-α/PPAR-γ,and PPAR-β/PPAR-γ for EMs.Results The expression levels of PPAR-α,PPAR-β and PPAR-γ in the lesion tis-sues of the experimental group were significantly higher than those of the control group(P<0.05).In the pa-tients with EMs,PPAR-α was predominantly expressed(P<0.05),whereas in the patients with MCTO,PPAR-γ was predominantly expressed(P<0.05).In the ROC curve of PPAR-α/PPAR-β ratio for diagnosing EMs,when the cutoff value was 1.251,the area under the curve(AUC)was 0.65(95%CI:0.51-0.80),the sensitivity was 90.00%,and the specificity was 50.00%.In the ROC curve of PPAR-α/PPAR-γ ratio for diag-nosing EMs,when the cutoff value was 0.817,AUC was 0.88(95%CI:0.78-0.99),the sensitivity was 96.67%and the specificity was 80.00%.In the curve of the PPAR-β/PPAR-γ ratio for diagnosing EMs,when the cutoff value was 0.755,AUC was 0.91(95%CI:0.82-1.00),the sensitivity was 100.00%,and the speci-ficity was 86.67%.Conclusion The expression of PPAR-α in the ectopic lesion tissues of the patients with EMs is significantly higher than that of PPAR-β and PPAR-γ,while in lesion tissues of the patients with MC-TO,the PPAR-γ expression is predominant.The PPAR-β/PPAR-γ ratio may become a potential biomarker for diagnosing EMs.
6.The water-soluble TF3 component from Eupolyphaga sinensis Walker promotes tibial fracture healing in rats by promoting osteoblast proliferation and angiogenesis
Binghao Shao ; Xing Chen ; Jin' ; ge Du ; Shuang Zou ; Zhaolong Chen ; Jing Wang ; Huaying Jiang ; Ruifang Lu ; Wenlan Wang ; Chunmei Wang
Journal of Traditional Chinese Medical Sciences 2024;11(2):245-254
Objective:
To determine the active components of Eupolyphaga sinensis Walker (Tu Bie Chong) and explore the mechanisms underlying its fracture-healing ability.
Methods:
A modified Einhorn method was used to develop a rat tibial fracture model. Progression of bone healing was assessed using radiological methods. Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site. Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration. The Transwell assay was used to explore the invasion capacity of the cells. Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells (HUVECs). qRT-PCR was used to evaluate the changes in gene transcription levels.
Results:
Tu Bie Chong fraction 3 (TF3) significantly shortened the fracture healing time in model rats. X-ray results showed that on day 14, fracture healing in the TF3 treatment group was significantly better than that in the control group (P = .0086). Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group. In vitro, TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs (all P < .01). Transwell assays showed that TF3 promoted the migration of HUVECs, but inhibited the migration of MC3T3-E1 cells. Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules. Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA, SPOCD1, NGF, and NGFR in HUVECs. In MC3T3-E1 cells, the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment.
Conclusion
TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.
7.Predictive value of disulfidptosis-related genes in the prognosis and drug sensitivity of colorectal cancer
Shuang-Yi SUN ; Xin-Xin HE ; Wen-Tong CHEN ; Bin LYU ; Meng-Xiao GE ; Yu-Meng GUO
Fudan University Journal of Medical Sciences 2024;51(4):473-483
Objective To establish a scoring model for predicting the prognosis and drug sensitivity of colorectal cancer(CRC)based on the expression of disulfidptosis-related genes by bioinformatics analyses combined with the validation with CRC patient-derived organoids(CRC-PDOs).Methods NMF(non-negative Matrix Factorization)algorithm,Cox and LASSO regression analyses were used to identify disulfidptosis-related genes with predictive value for CRC prognosis,and disulfidptosis-related risk scoring formula was constructed.The differential genes and enrichment pathways among different clusters were analyzed by GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes).The sensitivity of the high/low-risk clusters of CRC patients to chemotherapy drugs was predicted using the GDSC database and validated using CRC-PDOs.Results The results of NMF algorithm showed that CRC patients could be grouped into two clusters based on the disulfidptosis-related genes.COX regression analysis demonstrated that LRPPRC and SLC7A11 were the only two genes with significance to predict the prognosis of CRC patients(P=0.047,0.033).Low expression of SLC7A11 or high expression of LRPPRC in tumors of CRC patients was significantly correlated with overall survival(OS)(P=0.004,0.003).Based on LASSO regression analysis,the mortality risk scoring formula for disulfidptosis was as follows:Risk score=LRPPRC×(-0.670 5)+SLC7A11×0.311 2,and the GSE161158 dataset could be re-grouped into high-risk and low-risk clusters accordingly.There were 125 differentially expressed genes(DEGs)between the two clusters.According to the GO and KEGG results,the up-regulated genes in high-risk cluster were mainly enriched in immune regulation,such as leukocyte chemotaxis,granulocyte migration and toll-like receptor binding.Low-risk cluster was characterized by pathways associated with sulfide metabolism,such as sulfur compound transmembrane transporter activity.Based on the GDSC database,the expression level of SLC7A11 and LRPPRC could predict chemotherapy drug sensitivity.As a representative,the efficacy of chemotherapy drug(irinotecan)on inhibiting the growth of CRC-PDOs was shown to be linearly correlated with the relative gene expression levels of SLC7A11 and LRPPRC in CRC tissues of patients(P=0.007,0.040).Conclusion According to the results based on the bioinformatics analyses and drug sensitivity testing on CRC-PDOs,disulfidptosis risk score could predict the prognosis and drug sensitivity of CRC patients,with potential clinical application prospect.
8.Anti-inflammatory material basis and mechanism of Artemisia stolonifera based on UPLC-Q-TOF-MS combined with network pharmacology and molecular docking.
Le CHEN ; Yun-Yun ZHU ; Li-Ping KANG ; Chao-Wei GUO ; Yu-Qiao WANG ; Shuang-Ge LI ; Hong-Zhi DU ; Da-Hui LIU
China Journal of Chinese Materia Medica 2023;48(14):3701-3714
This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.
Antioxidants/chemistry*
;
Molecular Docking Simulation
;
Artemisia
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Network Pharmacology
;
Phosphatidylinositol 3-Kinases
;
Anti-Inflammatory Agents/chemistry*
;
Drugs, Chinese Herbal/pharmacology*
;
Interleukin-6
9.Effects of shading intensity on growth and quality of Artemisia stolonifera.
Shuang-Ge LI ; Ya-Chen ZHAO ; Hui LI ; Xian-Zhang HUANG ; Ting WU ; Mi LEI ; Da-Hui LIU
China Journal of Chinese Materia Medica 2023;48(14):3715-3721
The purpose of this study was to analyze the effects of shading intensity on the growth, yield, and quality of Artemisia stolonifera so as to provide references for the artificial cultivation of A. stolonifera. The seedlings of A. stolonifera with consistent growth underwent shading treatment at four shading intensity levels(0, 55%, 85%, and 95%) with different layers of black shading nets. The agronomic indexes, yield, moxa yield, total ash, quality characteristics of moxa during combustion and pyrolysis, main volatile components, flavonoids, and phenolic acids were measured. The results showed that under shading conditions, the stem diameter, leaf width, 5-leaf spacing, branch number, and yield of A. stolonifera decreased significantly, while the plant height, leaf length, leaf number, chlorophyll content, and moxa yield increased first and then decreased with the increase in shading intensity. The burning performance of moxa under natural light was better than that under moderate and severe shading conditions. The content of eucalyptol first increased and then decreased with the increase in shading intensity. The humulene content was negatively correlated with shading intensity. Other major volatile components showed no significant difference under various shading conditions. The content of neochlorogenic acid, cryptochlorogenic acid, isoschaftoside, and isochlorogenic acid B was positively correlated with shading intensity, while the content of chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C decreased first and then increased with the increase in shading intensity. To sum up, A. stolonifera is a light-loving plant, and shading can greatly reduce the yield, the content of internal components, and the burning performance of moxa. It is the main reason why A. stolonifera is mainly distributed in the forest edge, open forest, roadside, and wasteland grass in the middle and high mountains in the wild. For artificial domestication and cultivation of A. stolonifera, it is better to select plots with sufficient light.
10.Comparison of growth and quality of wild and cultivated Artemisia stolonifera.
Shuang-Ge LI ; Ya-Chen ZHAO ; Hui LI ; Xian-Zhang HUANG ; Ting WU ; Hong-Zhi DU ; Da-Hui LIU
China Journal of Chinese Materia Medica 2023;48(14):3722-3729
This paper aims to compare the difference of growth and quality between wild and cultivated Artemisia stolonifera, thereby providing references for further development and utilization of A. stolonifera. The wild and cultivated A. stolonifera from different altitudes were collected, and the agronomic characters, moxa yield, volatile components, flavonoids, and phenolic acids were determined. The results showed that the cultivated species were taller and stronger, with more leaves and branches, than the wild species. The moxa yield and combustion quality of wild products were higher than those of cultivated products. The content of main volatile components in cultivated products was higher than that in wild products. The content of flavonoids and phenolic acids in wild products was higher than that in cultivated products. At high altitude, the ignition performance, combustion persistence, comprehensive combustion performance, and heat release during combustion of the wild and cultivated A. stolonifera. were optimal. At middle altitude, the content of main characteristic volatile components and flavone phenolic acids in the leaves of the cultivated and wild A. stolonifera were the highest. At low altitude, the combustion quality and the content of the above components of the cultivated A. stolonifera decrease significantly. Considering the combustion quality and the content of the internal components of the leaf lint, the middle and high altitude areas are suitable for the artificial cultivation of A. stolonifera.
Artemisia
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Agriculture
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Flavonoids
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Plant Leaves
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Drugs, Chinese Herbal


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