1.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.
2.Effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis
Rui-hong ZHOU ; Xun-ya HOU ; Xiang-hui CHENG ; Jie PAN ; Ru-yi LAI ; Gui-mei CHEN ; Hui ZHANG ; Lan-jun WEI ; Lu ZHANG ; Jia-xin LIU
Chinese Journal of Schistosomiasis Control 2022;34(6):626-629
Objective To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. Methods A “admission-hospitalization-discharge” whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. Results The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = −7.688, −3.576 and −4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ2 = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ2 = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ2 = 11.767, P < 0.01). Conclusions The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients’ cure.
3. Analysis on the influencing factors of low back pain in the occupational workers of key industries in China
Hui-jie ZHANG ; Xin SUN ; Hua-dong ZHANG ; Rui-jie LING ; Yi-min LIU ; Gang LI ; Zao-liang REN ; Yan YIN ; Hua SHAO ; Heng-dong ZHANG ; Bing QIU ; Mei-bian ZHANG ; Da-yu WANG ; Qiang ZENG ; Ru-gang WANG ; Jian-chao CHEN ; Dan-ying ZHANG ; Liang-ying MEI ; Yong-quan LIU ; Ji-xiang LIU ; Cheng-yun ZHANG ; Tian-lai LI ; Qing XU ; Ying QU ; Xue-yan ZHANG ; Ning JIA ; Zhong-xu WANG
China Occupational Medicine 2021;48(05):481-487
OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.
4.Effect of rational emotive therapy on negative emotion in advanced schistosomiasis patients with repeated hospitalization
Rui-Hong ZHOU ; Hui-Qiong YU ; Jia-Xin LIU ; Cui-Lan XIAO ; Jie PAN ; Ru-Yi LAI ; Li-Le LI
Chinese Journal of Schistosomiasis Control 2020;32(3):308-310
Objective To examine the effect of rational emotive therapy on negative emotions among advanced schistosomiasis patients with repeated hospitalizations. Methods A total of 97 advanced schistosomiasis patients with anxiety and depressive emotions that were hospitalized in Xiangyue Hospital of Hunan Institute of Schistosomiasis Control for three times or more were enrolled, and given rational emotive therapy for 4 weeks in addition to routine nursing care. The scores for anxiety, depression and quality of life were estimated in patients before and after the rational emotive therapy using the Self-Rating Anxiety Scale (SRS), the Self-Rating Depression Scale (SDS) and WHOQOL-BREF Form. Results The SAS and SDS scores were significantly lower 4 weeks following rational emotive therapy than before the intervention (SAS score, 45.40 ± 7.77 vs. 59.25 ± 9.29, t = 14.021, P < 0.01; 51.48 ± 8.01 vs. 63.93 ± 9.59, t = 12.991, P < 0.01). The percentages of patients with moderate and severe anxiety and depression were significantly lower 4 weeks following rational emotive therapy than before the intervention (P < 0.01), and the scores for each item in the quality of life were all significantly greater 4 weeks following rational emotive therapy than before the intervention (P < 0.01). Conclusion Rational emotive therapy may improve the negative emotions and the quality of life of advanced schistosomiasis patients with repeated hospitalizations.
5.Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency.
Ting CHEN ; Fan TONG ; Xiao-Yu WU ; Ling ZHU ; Qiu-Zi YI ; Jing ZHENG ; Ru-Lai YANG ; Zheng-Yan ZHAO ; Xiao-Hui CANG ; Qiang SHU ; Ping-Ping JIANG
Journal of Zhejiang University. Science. B 2020;21(11):885-896
The pathogenesis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is highly heterogeneous and still unclear. Additional novel variants have been recently detected in the population. The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization. To address this problem, we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency. Marked deficiencies in fatty acid oxidation (FAO) and other mitochondrial defects were observed in cells carrying one of these six variants (c.541C>T, c.863T>G, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A), including reductions in mitochondrial respiratory-chain function and adenosine triphosphate (ATP) production, and increased levels of mitochondrial reactive oxygen species (ROS). Intriguingly, higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress. Moreover, the stability of the mutant homodimer was disturbed, and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics (MD) simulation. The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.
6.Expressions and Clinical Implication of UBE2 Family and UBE2T Gene in Lung Adenocarcinoma Based on Bioinformatics
Hao-shuai YANG ; Hui-na LAI ; Yi-ru RAO ; Xiao-ping LIN
Journal of Sun Yat-sen University(Medical Sciences) 2020;41(3):445-451
【Objective】 To investigate the expressions of ubiquitin-conjugating enzyme(UBE2) family and ubiquitin-conjugating enzyme E2T(UBE2T) gene and their relationships with the clinicopathology in lung adenocarcinoma. 【Methods】 Based on Linkedomics database, the expression levels of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA and their associations with the clinical characteristics of lung adenocarcinoma were collected and detected. Kruskal-Wallis H test was applied to compare the differences of pathologic stage, T stage and N stage, Wilcoxon rank sum test for M stage and Cox regression test for overall survival(OS). The expression profiles of UBE2T gene in lung adenocarcinoma and paracancerous tissues were obtained from the Cancer Genome Atlas(TCGA) database and then analyzed with independent samples t test. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway and the enrichment were examined by using Gene Set Enrichment Analysis(GSEA) software. 【Results】 The expressions of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA correlated with the clinicopathological features of lung adenocarcinoma. Compared with low UBE2T expression, high UBE2T expression predicted shorter OS time and advanced TNM stage. Their differences were statistically significant(P < 0.05). The UBE2T mRNA expression level was significantly upregulated in lung adenocarcinoma(P < 0.01). The gene enrichment analysis showed that the overexpression of UBE2T was closely related to 36 signal pathways(FDR < 0.05), including cell cycle(FDR = 0), spliceosome(FDR = 0), DNA repair(FDR = 0) and the glucose metabolism. The expressions of UBE2C, UBE2M, UBE2S, UBE2T and UBE2V2 mRNA in UBE2 family correlated with the clinicopathological features of lung adenocarcinoma. UBE2T was further identified as a factor most closely related with pathological grade, prognosis in lung adenocarcinoma and glycolysis process of tumor cells. 【Conclusion】 UBE2 family correlates with clinicopathological features of lung adenocarcinoma. UBE2T mRNA could be a new biomarker for lung adenocarcinoma.
7.Thyroid fine-needle aspiration cytology in Taiwan: a nationwide survey and literature update
Chien-Chin CHEN ; Jen-Fan HANG ; Chih-Yi LIU ; Yeh-Han WANG ; Chiung-Ru LAI
Journal of Pathology and Translational Medicine 2020;54(5):361-366
In Taiwan, thyroid fine-needle aspiration cytology is easily accessible and reliable for evaluating thyroid nodules. The sonographic pattern plays a major role and is the deciding factor for aspiration. We conducted a nationwide survey in 2017 and it revealed that 31% of laboratories had adopted The Bethesda System for Reporting Thyroid Cytopathology. There was a relatively high unsatisfactory rate (24.04%) and low rates of indeterminate diagnoses, including atypia of undetermined significance/follicular lesions of undetermined significance: 4.87%, and follicular neoplasm/suspicious for a follicular neoplasm: 0.35%. Moreover, the risks of malignancy in benign, atypia of undetermined significance, and suspicious for a follicular neoplasm were relatively high. These may reflect strict diagnostic criteria for indeterminate categories and better patient selection for surgery. Improvements in specimen sampling and continuing education programs are crucial. Newly-developed thyroid cytology technologies, such as immunocytochemistry, molecular testing, and computerized cytomorphometry, may further facilitate cytology diagnoses.
8. Anti-tumor activity of a recombinant endoglin-MIP3α Fc-fusion protein in mice with hepatocellular carcinoma
Zhi-Hui HE ; Si-Ru LIU ; Xin-Lai WU ; Yong-Hao HUANG ; Yan CHEN ; Yi DENG ; Pan-Pan XIE ; Yan-Da LU
Asian Pacific Journal of Tropical Medicine 2019;12(14):54-58
Objective: To investigate the effects of a recombinant endoglin-macrophage inflammatory protein 3α Fc-fusion protein (EM) vaccine on tumor angiogenesis and growth in mice with H22 hepatocellular carcinoma. Methods: An in vivo hepatoma mouse model was established. Seven days after subcutaneous inoculation of H22 tumor cells, mice were randomly divided into four groups: EM, endoglin Fc-fusion protein, macrophage inflammatory protein 3α Fc-fusion protein, and normal saline groups. Tumor volume and survival rate of mice were studied at 3-day intervals. Microvessel density of the tumors and tumor cell proliferation were detected by immunohistochemistry, and tumor cell apoptosis was detected by TdT-mediated biotinylated-dUTP nick-end label staining. The number of CD11c and CD86 positive dendritic cells were detected by flow cytometry. Results: Compared with the other groups, the tumor volume became smaller, and the survival time was longer in the EM-treated group. Besides, microvessel density and cell proliferation index were significantly lower, while the tumor cell apoptosis index was significantly higher in the EM-treated group. Besides the number of CD11c and CD86 positive dendritic cells in EM-treated mice was larger than that in other groups. Conclusions: EM Fc-fusion protein could effectively inhibit tumor growth through inhibiting endoglin-related tumor angiogenesis and cell proliferation, promoting tumor cell apoptosis, and could induce a certain degree of antitumor immune responses.
9.Effect and mechanism of astragaloside Ⅳ on Toll-like receptor pathway in fibrotic mice after renal ischemia-reperfusion.
Ru-Qian YANG ; Qian XU ; Zhi-Min HUANGFU ; Chun-Lai ZHANG ; Yi-Feng YIN ; Jie ZHANG ; Chun-Ling ZHAO
China Journal of Chinese Materia Medica 2018;43(18):3729-3739
The aim of this paper is to study the effect of astragaloside Ⅳ on renal fibrosis mice with ischemia-reperfusion injury (IRI) and discuss the mechanism. Male C57BL/6 50 mice were randomly divided into four groups, namely Sham-operated group, model group, AS-Ⅳ prevention group and AS-Ⅳ treatment group. Since the day of surgery, the mice in astragaloside Ⅳ prevention group were treated with astragaloside Ⅳ by gavage for 30 days at the dose of 30 mg·kg⁻¹·d⁻¹. At the 60th day after surgery, the mice in astragaloside Ⅳ treatment group were treated with astragaloside Ⅳ 100 by gavage for 30 days at the dose of 30 mg·kg⁻¹·d⁻¹. The mice in Sham-operated group and model group were treated with double distilled water containing 0.1% ethanol instead of astragaloside Ⅳ. Serum creatinine and blood urea nitrogen were detected by chemical methods. Histopathological changes and collagen deposition of affected kidneys were observed under optical microscope by HE and Masson staining. The expression levels of Toll like receptor pathway related molecules (TLR4,MyD88,TRAF6,TRAM,TRIF,NF-κB,TNF-α,IL-6, IFN-) in affected kidneys were observed by immunohistochemistry, Western blot methods and reverse transcription-PCR atprotein and mRNA levels in each group. The results showed that the degrees of fibrosis and histopathological damage of affected kidneys of mice in model group were the most obvious. And the expression levels of TLR4/MyD88 dependent signaling pathway-related molecules (TLR4 and MyD88, TRAF6 and NF-κB) in affected kidneys of mice in model group were the highest. At the same time, there was no difference in the expression levels of TLR4/MyD88 independent signaling pathway-related molecules(TRAM, TRIF)among sham-operated group, model group, astragaloside IV prevention group and astragaloside Ⅳ treatment group. In astragaloside Ⅳ prevention group and astragaloside Ⅳ treatment group, the injury of affected kidney was obviously reduced, and the protein expression levels of TLR4/MyD88 dependent signaling pathway-related molecules were also correspondingly reduced; at the same time, the expressions of terminal inflammatory cytokines (TNF-α,IL-6, IFN-) were suppressed. Therefore, astragaloside Ⅳ may improve renal interstitial fibrosis in mice after IRI by inhibiting the expression of TLR4/MyD88 dependent signaling pathway and the release of inflammatory cytokines (TNF-α,IL-6, IFN-), while the TLR4/MyD88 independent signaling pathway may not be involved in the process of renal fibrosis after ischemia-reperfusion injury.
10.Comparison of Ultrasound Features of Primary Metastatic Papillary Thyroid Carcinoma and Recurrent/Persistent Metastatic Cervical Lymph Nodes.
Jing-Zhu XU ; Zhi-Yong LIANG ; Xing-Hua WANG ; Xiao-Yi LI ; Hong-Feng LIU ; Qiong WU ; Ru-Yu LIU ; Xiao YANG ; Shen-Ling ZHU ; Rui-Na ZHAO ; Xing-Jian LAI ; Xiao-Yan ZHANG ; Xue-Hua XI ; Bo ZHANG
Acta Academiae Medicinae Sinicae 2017;39(5):675-681
Objective To explore the ultrasound features and levels of cervical lymph node metastases in primary and recurrent/persistent papillary thyroid cancer (PTC).Methods We retrospectively analyzed the clinical data of 2181 patients who underwent cervical lymph nodes dissection for PTC from January 12015 to January 12016.Totally 418 PTC patients (with 622 lymph nodes) who met the inclusion criteria entered the final analysis.Patients who had not received any prior thyroid treatment (surgery with or without radioactive iodine) were categorized as the primary group (352 patients with 527 metastatic lymph nodes),and patients who had received prior treatment (thyroidectomy with or without radioactive iodine) for PTC were categorized as recurrent/persistent group (66 patients with 95 metastatic lymph nodes).Pathological results from lymph node dissections were used as the gold standards by means of level-to-level analysis.Results The mean of the minimum axis diameter of the lymph nodes in the primary group was (6.7±3.6)mm,and that of the recurrent/persistent group was (6.6±3.1)mm (U=0.180,P=0.857).The proportion of metastasis in the central area of primary group was 40.0%,which was significantly higher than that in the recurrent/persistent group (12.6%);the proportion of metastasis in the lateral area was 60.6% in the primary group,which was significantly lower than that in the recurrent/persistent group (87.4%)(χ=26.288,P<0.001).In lateral metastatic lymph nodes,Ⅲ level was the most common place in both groups.Level Ⅴ metastatic lymph was rare in both primary group and recurrent/persistent group.Calcifications (63.1% vs. 48.2%;χ=7.207,P=0.007) and peripheral vascularity (81.1% vs. 59.4%;χ= 16.147, P<0.001) were more common in the recurrent/persistent group.The round shape,absence of an echogenic hilum,hyperechogenicity,and cystic aspects were not significantly different between these two groups (all P>0.05).Conclusions Primary metastatic lymph nodes often occur in the central area of lymph nodes,while lateral metastatic lymph nodes are more common in recurrent/persistent PTC.For metastatic lymph nodes,calcifications and peripheral vascularity are more common in recurrent/persistent PTC.

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