1.Activin and Hepatocyte Growth Factor Promotes Colorectal Cancer Stemness and Metastasis through FOXM1/SOX2/CXCR4Signaling
Hong PENG ; Ting YE ; Lei DENG ; Xiaofang YANG ; Qingling LI ; Jin TONG ; Jinjun GUO
Gut and Liver 2024;18(3):476-488
Background/Aims:
Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear.
Methods:
In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored.
Results:
Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133 + subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells.Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis.
Conclusions
Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.
2.Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19.
Xiaoyan LIU ; Zhe LI ; Shuai LIU ; Jing SUN ; Zhanghua CHEN ; Min JIANG ; Qingling ZHANG ; Yinghua WEI ; Xin WANG ; Yi-You HUANG ; Yinyi SHI ; Yanhui XU ; Huifang XIAN ; Fan BAI ; Changxing OU ; Bei XIONG ; Andrew M LEW ; Jun CUI ; Rongli FANG ; Hui HUANG ; Jincun ZHAO ; Xuechuan HONG ; Yuxia ZHANG ; Fuling ZHOU ; Hai-Bin LUO
Acta Pharmaceutica Sinica B 2020;10(7):1205-1215
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.
3.Study on the correlation between iodine nutrition level and thyroid diseases in some areas of Ningxia
Liping SHA ; Ting WANG ; Qingling LU ; Haidong ZHANG ; Haili XUE ; Jinlian WANG ; Wei ZHAO ; Daoyan LI ; Hong LEI ; Lanjie HE
Chinese Journal of Endocrinology and Metabolism 2018;34(5):394-397
Objective To investigate the correlation between iodine nutritional status and thyroid diseases in some areas of Ningxia. Methods The physical examination, questionnaire survey, and measurement of urine iodine, thyroid function, thyroid associated antibodies were performed, with thyroid ultrasonography in Jingyuan County, Xingqing District and Guyuan City, Ningxia Yinchuan City, totally including 2827 adults. Results The median urinary iodine of all subjects was 258. 7(76. 6-1506. 4) μg/L. The average level of urinary iodine in rural areas [203.3(64. 6-1154)μg/L] was lower than that in cities[340. 7(114. 8-1726. 1)μg/L, Z=19. 514, P>0. 01]. The average urinary iodine level was lower in people over 65 years old[234. 2(58. 9-2285. 4) μg/L, x2=6.449, P=0. 040]. Subjects in hypothyroidism group [232. 5(69. 2-1682. 3) μg/L] had the lowest average urinary iodine level, while hyperthyroidism group[331. 9(102. 4-1862) μg/L] turned to be the highest group( x2=15. 432, P>0. 01). Compared with the normal group, TPOAb and TGAb increased group had similar median levels of urinary iodine (P>0. 05). If compared with single nodule, multiple nodules group and the normal group's median levels of urinary iodine also had no significant difference(P>0. 05). Conclusion Iodine excess was found in the studied population in these areas of Ningxia.
4.Application effect of fast track surgery for patients with esophageal cancer: A systematic review and meta-analysis
LIU Jingjing ; LU Jiaju ; SHI Jiang ; LIN Qingling ; GUO Hong ; TIAN Jinhui ; LIU Jian ; YANG Kehu
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2018;25(7):596-603
Objective To evaluate the effect of fast track surgery (FTS) after esophageal cancer surgery. Methods The randomized controlled trial (RCT) and observational studies about FTS for esophageal cancer in PubMed、EMbase、The Cochrane Library、Web of Science、CBM、CNKI and WanFang databases were searched up to May 2017. Then the studies were screened according to the inclusion and exclusion criteria by two researchers. Data were analyzed by Stata12.0 software. Results Totally 13 RCTs and 5 observational studies with 2 447 patients were eligible for analysis. Compared with the control group, incidence of postoperative complications (OR=0.53, 95%CI 0.40 to 0.71, P<0.05) significantly reduced in the FTS group, but there was no significant difference between the two groups in readmission rate (OR=1.21, 95%CI 0.83 to 1.76, P=0.313) and 30 d mortality rate (OR=0.72, 95%CI 0.43 to 1.20, P=0.207). Conclusion FTS can safely and effectively accelerate the recovery of patients with esophageal cancer and it owns important clinical values.
5.Expression of VEGF, NRP1 and cancer stem cell marker CD44 in gastric carcinoma and their correlations
Jiajia YANG ; Lin ZHANG ; Maojin ZHENG ; Qingling WANG ; Yuting XU ; Hong LIU
Chinese Journal of Clinical and Experimental Pathology 2015;(2):124-127,131
Purpose To investigate the expression of VEGF, NRP1 and the cancer stem cell marker CD44 in gastric carcinoma and their correlations. Methods High throughput technology of tissue microarray and immunohistochemical SP method were employed to investigate the expression of VEGF, NRP1 and CD44 proteins in 72 gastric carcinoma specimens and 52 normal gastric tissues. Immu-nohistochemistry records were reviewed, their correlations and the clinicopathological characteristics were evaluated. Results ( 1 ) The positive rates of VEGF, NRP1 and CD44 proteins were 76. 4%, 66. 7%, and 83. 3% in gastric carcinoma, respectively, with sig-nificant differences from normal gastric tissues (P<0. 01). (2) The positive expression of VEGF and NRP1 were closely correlated with infiltration depth, lymph node metastasis and TNM stage (P<0. 05). The positive expression of CD44 was closely correlated with Lauren type, differentiation degree, lymph node metastasis and TNM stage (P<0. 05). (3) In addition, the expression of CD44 was significantly correlated with VEGF and NRP1 in gastric carcinoma (rs =0. 578, rs =0. 278, rs =0. 316, P<0. 05). Conclusions VEGF, NRP1 and the cancer stem cell marker CD44 are highly expressed in gastric cancer, which are closely related to the biological behaviors of gastric cancer. Synergistic effects are observed between VEGF and NRP1, and they are closely related to the expression of the cancer stem cell marker CD44, which remains to be further studied.
6.Clinical study of hand foot and month disease with acute flaccid paralysis
Dongyue YANG ; Xiuhua DAI ; Qingling TIAN ; Xue FENG ; Peng SONG ; Yuan HONG
Chinese Pediatric Emergency Medicine 2015;22(11):762-766
Objective To investigate the epidemiological and clinical characteristics and prognosis of 31 children with hand foot and mouth disease(HFMD) complicated with acute flaccid paralysis(AFP).Methods Thirty-one HFMD children complicated with AFP served as study objective,who were admitted to Tangshan Maternity and Children Health Hospital from Jun 2011 to Dec 2014.The clinical manifestations and follow-up outcomes of 31 children with HFMD followed by AFP were retrospectively reviewed.Results Participants in this study consisted of 31 children(16 males,15 females,age from 3 months to 9 years) who met the criteria for HFMD with AFP.Among the 31 cases,27(87.1%)cases were less than 3 years old and 29(93.5%) cases were from countryside.Eleven cases (35.5%)were infected by enterovirus 71,1 case (3.2%) was infected with coxsackieviruses A16 and 19 cases(61.3%) were infected by other enteroviruses.AFP developed(7.1 ±2.9) days after the onset of fever and progressed to maximum severity within 1-2 days.All of the cases presented with fever and skin rash,38.7% cases presented with limbs tremor and 87.1% cases presented with startle and skip.Besides AFP of limbs, 100% cases complicated with encephalitis.Thirty-one cases showed poliomyelitis-like syndrome(20 cases with one flaccid limb,5 cases with lower limbs,4 cases with upper limbs and 2 cases with left hemiplegia).In these cases, the muscle power varied from level 0 to level 4.The muscle strengthen and muscle tone in 21 patients were recovered within 2 weeks,and the other cases showed recovery 2 to 3 weeks later.After four weeks, the muscle strengthen in 19 cases recovered to 5 level(10 cases with single lower limb,5 cases with single upper limb,3 cases with two lower limbs and 1 case with two upper limbs).Conclusion HFMD complicated with AFP most commonly occurs in children aged less than 3 years old.The majority of cases were from countryside.Enterovirus 71 is still relatively common pathogen.All the 31 cases complicated with encephalitis.Cases clinically presented one flaccid limb, lower limbs, upper limbs and hemiplegia.AFP may be to some degree reversible in HFMD cases.In most cases described here, paralysis occurred in a single lower extremity and recovered more rapidly than those with two fimbs affected or with single upper extremity impairment.
7.Correlation of liver X receptor and abnormal lipid metabolism in school-age children with obesity
Qingling ZHU ; Xinhua YE ; Shengping YANG ; Qian LIU ; Hong CHEN
Journal of Clinical Pediatrics 2014;(2):147-150
Objectives To explore the relevant factors of liver X receptor (LXR) and lipid metabolism in school-age chil-dren with obesity. Methods A total of 80 obese children were selected by indexes of physical growth from pupils in Grades 1-6, aged 7-14 years from June 2011 to October 2011. Fifty-one age and sex matched children with normal BMI were chosen as nor-mal controls. The metabolic indexes including aspartate transaminase (AST), alanine aminotransferase (ALT), glutamyl transpep-tidase (GGT), total cholesterol (CHOL), triacylglycerol (TG), high density lipoprotein cholesterol (HDL-C), low density lipopro-tein cholesterol (LDL-C) and expression of LXR were detected in fasting blood. Results The expression level of LXR in obese children (9.14 ± 1.15) was higher than that in control children (2.84 ± 3.68) with significant difference (t=4.55,P=0.000). Eighty percent (80%) of obese children were LXR>1 (64/80) which was higher than that of control children (23/51, 45.1%), and signifi-cant difference was found between the two groups (χ2=17.01, P=0.000). Compared to controls, the levels of AST, ALT, GGT, CHOL, TG and LDL-C were higher while the level of HDL-C was lower in obese children (P<0.05). The correlation analysis found that AST, ALT, CHOL, LDL-C and BMI were positively correlated with LXR (r=0.18~0.26,P<0.05). Logistic regression ana-lysis showed that AST≥40IU/L (OR=1.076), ALT≥40IU/L (OR=1.036), CHOL≥5.20 mmol/L (OR=2.038), LDL-C≥3.36 mmol/L (OR=2.176) and BMI≥18.9 kg/m2 (OR=1.131) were risk factors for LXR>1 (P<0.05). Conclusions Obesity in school-age chil-dren can up-regulate the expression of liver X receptor and cause liver damage and abnormal lipids metabolism.
8.Application effect of evidence-based nursing and individual nursing in pregnancy patients with lupus nephritis
Ting CHEN ; Yanfang HE ; Peizhuang ZHENG ; Qingling HONG
The Journal of Practical Medicine 2014;(12):1996-1999
Objective To investigate the application effect of evidence-based nursing and individual nurs-ing in pregnancy patients with lupus nephritis. Methods Sixty-five patients were randomly divided into control group and observation group. They were treated with routine care and evidence-based nursing respectively. The complications, pregnancy outcome and satisfaction of patients were compared between the two groups. Results There were not significant difference in renal failure , pregnancy induced hypertension , ecalampsia , heart failure , HELLP syndrome and other complications between observation group and normal group (P > 0.05). The pregnan-cy outcome had no significant difference between two groups (P > 0.05). In observation group, the health score was significantly higher than that of control group(P < 0.05). The mental health score in control group was sig-nificantly higher than that of observation group (P < 0.05). There werenot significant difference in social health and overall health score between the two groups (P > 0.05). Conclusion The application of evidence-based nursing and individual nursing in pregnancy patients with LN not only reduce the incidence of complications , but also reduce the chance of premature birth, stillbirth. And it could improve the cognition on the nursing work of this disease and the satisfaction of patients. But individual nursing is better in improving the patient′s mental health, while the evidence-based nursing is better in improving the health status.
9.In vitro inhibitory effects of chlorogenic acid and isochlorogenic acid on Aspergillus fumigatus biofilm
Yiqiang CHEN ; Jinliang KONG ; Ke WANG ; Hong HUANG ; Lihong WU ; Qingling JING
Chinese Journal of Infection and Chemotherapy 2014;(4):327-333
Objective To investigate the in vitro destructive effect of chlorogenic acid (CRA)/isochlorogenic acid (IRC)on Aspergillus fumigatus biofilm in a model of biofilm formation.Methods The in vitro biofilm model was established using clinical isolates of A.fumigatus.The minimum inhibitory concentrations (MIC)of antimicrobial agents against A.fumigatus were determined by microdilution method.Scanning electron microscope (SEM)and laser confocal scanning microscope (CLSM)were used to characterize the biofilm.Crystal violet staining method was used for biofilm quantitation.Results After reaction with CRA/IRC for 24 h or 48 h,observation of biofilm showed that A.fumigatus extracellular matrix was thinner than the control group.Biofilm quantitation showed that the optical densities were 1.05±0.19,1.14±0.26,0.99±0.14 for CRA group (1 024 mg/L,512 mg/L,256 mg/L);1.39±0.06,1.41±0.06,1.60±0.04 for IRC group (1 000 mg/L,500 mg/L,250 mg/L)at 24 h,and 1.91±0.17 for control group (P<0.05).The quantitation of biofilm showed that the optical densities were 2.25±0.05,2.27±0.05,2.31±0.03 for CRA group,2.26 ± 0.02,2.27±0.02,2.29±0.04 for IRC group at 48 h,and 2.36±0.01 for control group (P<0.05).Conclusions CRA/IRC has some inhibitory effect on the formation of A.fumigatus biofilm.
10.Serum uric acid level and its related factors in school-age children with obesity
Qian LIU ; Weiying LIU ; Qingling ZHU ; Xinhua YE ; Xinhui YUAN ; Hong CHEN
Journal of Clinical Pediatrics 2013;(9):842-844
Objectives To investigate the serum uric acid level and its related factors in obese children. Methods Obese children were selected from all pupils (ages 7-14) of 3 primary schools. Age-and sex-matched children with normal body mass index (BMI) were chosen as normal controls. Fasting venous blood samples were collected to detect uric acid (UA), glucose (GLU), total cholesterol (CHOL), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipopro-tein cholesterol (LDL-C). Results Sixty-eight (2.2%) obese children (57 boys and 11 girls) were detected from 3 000 children. Compared with 136 normal controls, the blood pressure (BP), levels of UA, CHOL, TG and LDL-C, and waist circumference (WC) were higher while HDL-C was lower in obese children (P<0.05). The detection rate of hyperuricemia in obese children (35.3%) were signiifcantly higher than that in normal controls (5.9%) (P<0.05). UA was positively related with WC, BMI, BP and TG, negatively related with HDL-C. Conclusions Obesity can lead to higher serum UA, higher BP and abnormal lipid metabolism. The level of serum UA was correlated with BP and abnormal lipid metabolism.

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