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Table of Content
30 July 2024, Volume 36 Issue 4
Previous Issue
解密前列腺癌——从容和科学面对
SHOU Jianzhong
2024, 36(4): 253-255,260. doi:
10.3969/j.issn.1004-616x.2024.04.001
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Prostate cancer (PCa) is one of the most commonly diagnosed malignancy in men,and the incidence of PCa has been increasing in China over the past decade. There are several well-established risk factors for PCa,including age and family history of PCa. There is no specific symptom for PCa at early stage,thus it is of great significance to carry out screening and early detection for PCa. Prostate-specific antigen (PSA) testing is the main approach of screening for PCa,multiparametric MRI plays an important role in PCa diagnosis and staging,and TRUS-guided prostate biopsy is the standard of care. The management of PCa is based on the staging and risk stratification,and treatment strategy should be standardized and precise. Radical prostatectomy or external-beam radiation therapy is the gold standard for localized PCa. For metastatic PCa,treatment approaches with demonstrated survival benefit include androgen deprivation therapy combined with novel hormonal therapy,chemotherapy,targeted therapy,and radionuclide therapy.
胃肠间质瘤患者服用甲磺酸伊马替尼仿制药和原研药的血药浓度及安全性评估
CHEN Xinran, LIU Mingfeng, GUO Teng, DU Liying, HOU Juan, HUO Liman
2024, 36(4): 256-260. doi:
10.3969/j.issn.1004-616x.2024.04.002
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OBJECTIVE
:TTo evaluate the blood concentrations and safety among gastrointestinal stromal tumor patients treated with the generic or branded domestic imatinib,and to provide recommendations for their use.
METHODS
:From December 2020 to December 2023,information on gastrointestinal stromal tumor patients who were treated with imatinib mesylate in the Fourth Hospital of Hebei Medical University were collected. The patients were divided into the original research drug imatinib mesylate tablets group,generic imatinib mesylate tablets group,and generic drug imatinib mesylate capsule group. Steady-state trough concentrations of imatinib and its active metabolite,N-desmethyl matinib,were measured by ultra-performance liquid chromatography with the Triple Quad 4500 Mass Spectrometry System. All the adverse reactions were collected and determined according to Common Adverse Event Evaluation Standard 5.0 (CTCAE 5.0). Differences in the plasma concentrations and adverse effects among the three groups were analyzed.
RESULTS
:There were no significance differences in trough concentrations of imatinib,N-desmethyl imatinib,the sum of imatinib and N-desmethyl imatinib,and side reaction grades among the generic and the two branded groups (all
P
>0.05).
CONCLUSION
:The branded and generic drugs of Imatinib mesylate had the same safety profile among treated patients.
甲基丙烯酸缩水甘油酯通过ERK/MMP14信号通路影响16HBE细胞恶性转化的研究
CUI Xufang, WANG Quankai, JIN Huiping, LI Xinwei, GU Yiting, WUHAN Baolier, KANG Tongying, XU Jianning
2024, 36(4): 261-267. doi:
10.3969/j.issn.1004-616x.2024.04.003
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OBJECTIVE
:To investigate whether glycidyl methacrylate (GMA) would affect malignant transformation of human bronchial epithelial (16HBE) cells through the ERK/MMP14 signaling pathway,and to investigate its molecular mechanism for malignant transformation of the 16HBE cells.
METHODS
:16HBE cells which were repeatedly exposed to 8 μg/mL GMA were used as the GMA treatment group,and the cells treated with the same volume of dimethyl sulfoxide (DMSO) as the solvent control group. At the 40th passage of the 16HBE cells,they were harvested,and the degree of malignant transformation was identified using the soft agar clone formation assay. The wound healing and the transwell cell migration assays were used to detect the migration ability of cells. Western blot was used to verify expression of the MMP14 protein,and levels of ERK1/2 and its phosphorylated proteins. Quantitative real-time PCR (qPCR) was used to detect mRNA expression levels of MMP14 and of the key signal molecules of the ERK pathway:ERK1 and ERK2.
RESULTS
:The number of colonies formed by cells in the GMA-treated group in soft agar was greater than that in the DMSO-treated group (
P
<0.05). Results from the wound healing and the transwell cell migration assays showed that the migration ability of the GMA-treated 16HBE cells were significantly higher than those of the DMSO-treated control cells (
P
<0.05). Compared with the control cells,expression levels of MMP14 mRNA and protein in 16HBE cells were increased. The expression levels of p-ERK1/2 protein and ERK1 mRNA were also increased,and the differences were statistically significant (
P
<0.05),while there was no significant difference in ERK2 mRNA expression (
P
<0.05).
CONCLUSION
:The process of GMA-induced malignant transformation of 16HBE cells was associated with activation of the ERK/MMP14 signaling pathway. Our results are helpful for a better understanding of mechanism in GMA-induced malignant transformation of 16HBE cells.
二氧化硅暴露对呼吸道上皮细胞基因表达的影响
WU Mengyu, DE Xiaoming, SHAN Jing, LI Jie, ZHANG Yingchi, XU Haiming
2024, 36(4): 268-274,280. doi:
10.3969/j.issn.1004-616x.2024.04.004
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OBJECTIVE
:Bioinformatics method was used to explore changes of gene expression in NHBE cells exposed to SiO
2
and key genes were verified by experiments,to provide information for enhanced diagnosis and treatment of silicosis.
METHODS
:GSE62769,a dataset related to silica,was obtained from GEO database. The differentially expressed genes (DEGs),GO functional enrichment analysis and KEGG signal pathway analysis were carried out with R language 3.6.3. At the same time,the protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape software,and key genes were screened by MCODE plug-in. Finally,A549 cells were exposed to 0,50,100,200 μg/mL SiO
2
for 24 h and the bioinformatics analysis results of key gene expression levels were extensively verified by RT-qPCR method.
RESULTS
:A total of 48 DEGs were screened. The results of GO and KEGG analysis showed that DEGs were mainly involved in biological processes such as lipopolysaccharide reaction and reaction to bacterial molecules,etc.,and signal pathways such as cytokine-cytokine receptor interaction,etc. Eleven key genes of PPI network were selected by MCODE plug-in,which were
CXCL8
,
CXCL10
,
TLR2
,
JUN
,
ICAM1
,
CXCL1
,
MMP1
,
TNFAIP3
,
CCL20
,
CXCL2
and
CXCL3
.Results from RT-qPCR analyses showed that expressions of
CXCL8
,
JUN
,
ICAM1
,
CXCL1
,
MMP1
,
TNFAIP3
,
CCL20
and
CXCL3
were significantly up-regulated in the A549 cells treated with 200 μg/mL SiO
2
suspension,which was consistent with the trend of gene expression on NHBE cells in bioinformatics analysis.
CONCLUSION
:Based on bioinformatics and experimental verification methods,11 key DEG related to SiO
2
exposed respiratory epithelial cells were screened. Our results provided new information on pathogenesis of silicosis,and identified several possible targets for the early diagnosis and treatment of silicosis.
专利中药处方治疗放射性肺损伤的用药规律及作用机制研究
LI Mei, LI Jianhua, LIU Huan, WANG Zhipeng, GAO Jie, YUAN Hui, SUN Ge
2024, 36(4): 275-280. doi:
10.3969/j.issn.1004-616x.2024.04.005
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OBJECTIVE
:To collect the patent prescriptions of traditional Chinese medicine for the treatment of radiation-induced lung injury,and to understand their mechanisms of action.
METHODS
:The Chinese patent publication website of the State Intellectual Property Office Traditional Chinese medicine prescriptions for the treatment of radiation-induced lung injury was reviewed to collect relevant information and the data were correlated,clustered and subjected to complex networks analysis using the ancient and modern medical record cloud platform. The action targets and related pathways of the core prescription were investigated via network pharmacology.
RESULTS
:From the establishment of the database since August 2022,17 patents of Chinese medicine prescriptions (with 153 medicines) for the prevention and treatment of radiation-induced lung injury were filed. The most commonly used medicine included liquorice (9 times,52.94%) and Radix Rehmanniae (5 times,29.41%). Mechanistically,these Chinese medicine have been described as cold in four Qi,sweet in five flavor,lung in meridian,and heat clearing and detoxification in efficacy. The commonly used drug pairs are Radix Scrophulariae rehmanniae,bitter almond licorice,Houttuynia licorice,Radix Rehmanniae Scrophulariae. The core prescription consisted of licorice,Rehmannia glutinosa,bitter almond,Radix Scrophulariae and Houttuynia cordata. The main targets of the core prescriptions might be
JUN
,
IL-6
,
PTGS2
,
FOS
,
IL-8
,
IL-10
,etc. and the relevant action pathways included lipid and atherosclerosis,chemical carcinogenesis receptor activation,chemical carcinogenesis reactive oxygen species,PI3K Akt signaling pathway,MAPK signaling pathway,etc.
CONCLUSION
:Our investigation indicates that the therapeutic mechanism for the patent prescription of Chinese medicine was by clearing away heat and detoxification,cooling blood,supplementing spleen and Qi,and evacuating wind heat. The mechanism of action may be through inhibiting inflammatory reaction,thus alleviating radiation-induced lung injury.
雾化吸入NaClO致小鼠肺损伤模型的构建及机制研究
LI Jiawei, GUO Xiaojie, SHI Minjie, LI Wenli, LIU Jiangzheng
2024, 36(4): 281-287,297. doi:
10.3969/j.issn.1004-616x.2024.04.006
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OBJECTIVE
:To use a mouse lung injury model to investigated toxicity of inhaled NaClO disinfectant.
METHODS
:Mice were exposed by inhalation to 100 mmol/L NaClO of standard solution dissolved in 0.9% NaCl solution,with gradient dilution. Lung functions of mice were measured 24 h using a lung function instrument after infection. Blood samples d from the orbit and alveolar lavage fluid and lung tissues were collected and stained with HE. Organelles such as mitochondria in lung tissue cells were evaluated for morphology. TUNNEL staining was conducted for apoptosis. The BALF protein concentrations were measured by BCA. Cells of BALF were counted by FALCS,and analyzed using Western blot. The relative protein expression of antioxidant enzymes,apoptosis and autophagy were evaluated. The ELISA kit was used to detect inflammation-related protein content. The mRNA levels of antioxidant enzymes and inflammation were measured by qPCR. Lung tissue homogenates were analyzed for MDA content and SOD enzyme activity.
RESULTS
:Compared with the control group,the degrees of structural damage in the 75,150,300 μg/L NaClO infected groups were concentration dependent. The protein concentrations of 75 μg/L alveolar lavage fluid did not change significantly. The protein concentrations of the 150 and 300 μg/L NaClO infected groups increased significantly (
P
<0.05),and the cell number increased significantly (
P
<0.05). The 150 μg/L NaClO was selected as the study concentration. Compared with the control group,pulmonary function injury was increased (
P
<0.05), protein expressions of antioxidant enzymes SOD2 and Nrf2 were disturbed (
P
<0.05), mRNA levels of SOD2,Nrf2,and CAT were reduced (
P
<0.05). The protein concentrations of IL-1β and TNF-α in serum,alveolar lavage fluid and tissue homogenate were increased (
P
<0.05),with higher relative mRNA expression in the tissue homogenate (
P
<0.05),and a marked increase in the number of apoptotic cells. There was increased expression of Bax and cleaved caspase-3 proteins (
P
<0.05). Lung tissue cell mitochondria were significantly swollen,with the presence of autollysosomes,Beclin1, increased protein expression (
P
<0.05),and proprotein expression of P62 (
P
<0.01).
CONCLUSION
:A NaClO-induced mouse lung injury model was established which showed that NaClO could induce apoptosis,oxidative stress,inflammation and autophagy in mice.
分泌型卷曲相关蛋白4在肝细胞癌中的表达及其与患者临床病理指标和预后的关系
ZHU Wenbiao, YAN Chunmei, QIU Bo, XIE Shoucheng, XIAO Huanqin, LIU Gaomin
2024, 36(4): 288-293,297. doi:
10.3969/j.issn.1004-616x.2024.04.007
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OBJECTIVE
:To investigate expression of secreted frizzled-related protein 4 (sFRP4) in hepatocellular carcinoma (HCC) and relationship with clinicopathological index and prognosis.
METHODS
:Immunohistochemical methods were used to detect the expression of sFRP4 protein in 95 surgically resected HCC tissues and paracancerous tissues; patients clinicopathological indexes were used to analyze relationships with expression levels of the sFRP4 protein; the Kaplan-Meier survival curves were used to analyze relationships between expression of the sFRP4 protein and prognosis of the patients based on their clinicopathological index; and proportional hazards model (COX) was used to analyze factors affecting the prognosis of HCC patients.
RESULTS
:The positivity rate of sFRP4 protein was 48.42% (46/95) in HCC tissues and 85.26% (81/95) in paracancerous tissues. sFRP4 protein was therefore less positive in HCC tissues than in paracancerous tissues (
χ
2
=24.596,
P
<0.01). Its expression in HCC tissues were significant for different histological grade (
χ
2
=11.877,
P
<0.05),histological subtype (
χ
2
=3.873,
P
<0.05) and microvascular invasion (
χ
2
=6.493,
P
<0.05). Patients with the sFRP4 protein-negativity had significantly worse cumulative overall survival (OS) and cumulative disease-free survival (PFS) than that of the positive group (both
P
<0.01). Cox multivariate analysis showed that sFRP4 protein [
HR
=0.238,95%
CI
(0.138,0.412),
P
<0.01],clinical stage of hepatocellular carcinoma in China [
HR
=2.438,95%
CI
(1.256,4.730),
P
<0.01] were independent risk factors affecting the PFS after surgical resection of HCC. In addition,the sFRP4 protein [
HR
=0.226,95%
CI
(0.109,0.467),
P
<0.01] and histological grade [
HR
=2.236,95%
CI
(1.199,4.170),
P
<0.05] were independent risk factors affecting the OS after surgical resection of HCC.
CONCLUSION
:Expression levels of the sFRP4 protein were differentially significant between the HCC and paracancerous tissues,as well as with histological grade,histological subtype and microvascular invasion in HCC tissues. The sFRP4 protein-negative group of patients had a poorer prognosis. In addition,its expression level was an independent risk factor for the prognosis of these patients after surgical resection.
异丙隆原药对大鼠的致畸作用
CHENG Xiurong, WANG Haihua, CHEN Wei, LIANG Yifan, XIE Guangyun
2024, 36(4): 294-297. doi:
10.3969/j.issn.1004-616x.2024.04.008
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OBJECTIVE
:To investigate teratogenicity of isoproturon in rats.
METHODS
:Pregnant Wistar rats were divided into 4 groups of 15 rats per group. Control group (peanut oil) and isoproturon (36.9,73.8 and 369.0 mg/kg) were administered by gavage once per day from day 6
th
to 15
th
of gestation. Rats were killed at the 20
th
day of gestation,maternal and embryonic developmental indicators were examined.
RESULTS
:Compared to the control group,all observation indicators of 36.9 and 73.8 mg/kg of isoproturon group were no statistically significant difference (
P
>0.05). On the 9
th
day,the 369.0 mg/kg group showed signs of fatigue,fluffy back hair,and significantly lower body weight (
P
<0.01). The implantation counts and live fetus counts were lower (
P
<0.5),dead embryos were increased and the average body weight of the litters were significantly less than that in the control group (
P
<0.5,
P
<0.01). Abnormalities were observed such as widened fontanelle,occipital ossifications,and incomplete and rib bending. The skeleton malformation rate of 27.78% was increased compared to the control group (
P
<0.05).
CONCLUSION
:Under our conditions,369.0 mg/kg of isoproturon treatment induced maternal toxicity and embryonic developmental toxicity in Wistar rats.
脂肪酸代谢相关基因
ACSL1
在急性髓系白血病中的作用及潜在价值
CUI Jian, CHEN Ye, HE Li, BAO Ying, DONG Shaojuan, ZHU Danxia, WU Jun, CUI Mengying
2024, 36(4): 298-304. doi:
10.3969/j.issn.1004-616x.2024.04.009
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OBJECTIVE
:To analyze involvement of the fatty acid metabolism-related gene,long-chain esteryl-CoA synthetase 1 (ACSL1),in acute myeloid leukemia (AML) through bioinformatics analysis.
METHODS
:Expression levels of the
ACSL1
gene in AML patients and healthy controls were analyzed using the Gene Expression Profiling Interaction Analysis (GEPIA) database. The Kaplan-Meier survival curves for the ACSL1 high and low expression groups were plotted by using R-package survminer,and correlations between the
ACSL1
gene expression and the survival rate of AML patients were analyzed. The receiver operating characteristic (ROC) curve of ACSL1 was plotted using the timeROC package in R language to explore the diagnostic efficiency of
ACSL1
gene in controls and AML patients. Single gene enrichment analysis (GSEA) was used to clarify the oncogenic and lipid metabolism pathways of
ACSL1
gene. Kaplan-Meier survival analysis was used to determine relationships between ACSL1 expression level and overall survival (OS). Univariate and multivariate Cox regression analysis were used to establish a prognostic model and to determine whether ACSL1 was an independent prognostic factor for AML,and to investigate the prediction effect of the model.
RESULTS
:The expression levels of ACSL1 in AML patients were significantly higher than those in the controls (
P
<0.05),and they had high diagnostic significance for the AML patients. In addition,patients in the ACSL1 high expression group had poor survival and poor prognosis (
P
=0.045). The ROC curve showed that the area under the curve (AUC) of ACSL1 in diagnosing the 1-,2-,and 3-year survival time of AML patients was greater than 0.6,indicating that the prediction accuracy of ACSL1 was high. Enrichment analysis showed that ACSL1 played an important role in the occurrence and development of AML,mainly through fatty acid degradation and metabolism. Univariate Cox analysis showed that age and ACSL1 expression level were high-risk factors affecting the overall survival rate of AML patients (HR>1,
P
<0.05),and multivariate Cox analysis showed that age,chromosomal abnormality score and gene mutation score were independent factors affecting the prognosis of AML patients (
P
<0.05).
CONCLUSION
:
ACSL1
,a fatty acid metabolism-related gene,is highly expressed in AML,and enriched in multiple oncogenic and fatty acid metabolism pathways. Its high expression was closely related to poor prognosis and,therefore,the expression can be used as a potential therapeutic target and prognostic biomarker for AML.
血清MMP1和P53自身抗体联合检测对食管鳞状细胞癌的诊断价值
HUANG Xiaoyan, WU Fangcai, LIU Cantong, HUANG Jiatao, XU Yiwei
2024, 36(4): 305-308,324. doi:
10.3969/j.issn.1004-616x.2024.04.010
Abstract
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OBJECTIVE
:To evaluate diagnostic values from the combined detection of serum MMP1 and P53 autoantibody in patients with esophageal squamous cell carcinoma (ESCC).
METHODS
:The study included 93 ESCC patients hospitalized in the Cancer hospital of Shantou University Medical College and 90 physical examination subjects as normal controls. Serum levels of MMP1 and P53 autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA). The diagnostic value was evaluated using the receiver operating characteristic (ROC) curve.
RESULTS
:The serum levels of MMP1 and P53 autoantibodies of ESCC patients were higher than those in normal controls (
P
<0.01). ROC curves showed that the area under curve (AUC) of MMP1 in ESCC diagnosis was 0.700 (95%
CI
:0.624-0.776). When the optimum diagnostic cutoff was 7.248 ng/mL, the sensitivity was 52.7%,and the specificity was 83.3%. Measurement of P53 autoantibodies demonstrated an AUC of 0.713 (95%
CI
:0.638-0.788),with the diagnostic cutoff of 0.080 and a sensitivity/specificity of 49.5%/83.3%. The combination of MMP1 and P53 autoantibodies yielded an AUC of 0.787 (95%
CI
:0.720-0.854),a sensitivity of 66.7% and a specificity of 83.3%. In early-stage ESCC,combined detection of MMP1 and P53 autoantibodies provided good diagnostic power (AUC=0.760;95%
CI
:0.663-0.857),with 66.7% sensitivity and 83.3% specificity.
CONCLUSION
:Serum MMP1 and P53 autoantibody were both over-expressed in ESCC patients. The use of both biomarkers was helpful in making early diagnosis of ESCC.
水培生菜中锶的迁移富集及其生理影响
YAN Dong, LI Bin, LIANG Chenqing, HE Yingxue, FAN Li, JIANG Xiaoyan
2024, 36(4): 309-314,319. doi:
10.3969/j.issn.1004-616x.2024.04.011
Abstract
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OBJECTIVE
:The aim of this study was to investigate the migration and accumulation of strontium (Sr) in lettuce,as well as Sr's role on physiological effects in lettuce.
METHODS
:Lettuces were cultured using hydroponic method,with one control group (without Sr added) and five Sr treatment groups (0.1,0.5,1,5,and 10 mmol/L). The contents of calcium,iron,potassium,magnesium,sodium,phosphorus,sulfur and strontium in lettuce stem leaf and root tissues were detected by Inductively coupled plasma atomic emission spectrometry (ICP-AES),and the distributions of Sr in lettuce stem leaf and root tissues cells were analyzed by scanning electron microscope coupled X-ray energy dispersive spectrometer (SEM-EDX).
RESULTS
:The mass fractions of Ca,S,Sr in lettuce stems and leaves,and Sr in roots showed statistically significant differences under different Sr treatment groups (
P
<0.05). The transportation factors (TF) of S treated with 5 and 10 mmol/L Sr was lower than that of control group (
P
<0.05),and the TF values of Sr decreased with the increase of Sr concentration in culture solution. As the concentration of Sr in the hydroponic solution increased,the TF value of Sr showed a decreasing trend. The concentrations of S in the culture solution under 5 and 10 mmol/L Sr were significantly decreased compared with the control group,and the difference was statistically significant (
P
<0.05). Compared with the control group,the chlorophyll content (SPAD) values of lettuce treated with 5 and 10 mmol/L Sr were significantly increased (
P
<0.05). The weight percentage of Sr in lettuce tissue was as follows:leaf surface guard cell > epidermis,leaf cross section mesophyll ≈ epidermis,root cross section epidermis > pericycle > phloem.
CONCLUSION
:The mass fraction of Sr in lettuce root was higher than that in stem and leaf. With the increase of Sr treatment concentration,the proportions of Sr migrating from roots to leaves decreased,and the mass percentages of S in roots increased,and the SPAD values of leaves increased. The content of Sr absorbed by lettuce roots were mainly fixed on the epidermis of lettuce roots.
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