1.The biological mechanism and clinical application of boron neutron capture therapy
Pengxiang CHEN ; Qingxu SONG ; Bo CHENG ; Yuchen LIU ; Tianyu LIU ; Yufeng CHENG
Chinese Journal of Radiological Medicine and Protection 2023;43(10):845-850
Boron neutron capture therapy(BNCT), a promising radiotherapy, belongs to precision treatment for cancers. BNCT can accurately kill cancer cells and protect normal cells at the same time relying on 10B compounds with high efficacy. The research about developing new 10B compounds is in progress, and novel and efficient 10B compounds are emerging, which greatly facilitate broadening the advantages and efficacy of BNCT. Considering the mixed rays generated from the BNCT process, its biological effects on tumor cells are relatively complex, and related studies are still lacking. The molecular mechanisms underlying BNCT need to be elucidated further. BNCT has been applied in the treatment of malignant brain tumors, head and neck cancers, and malignant melanoma with favorable curative effects. This review mainly focuses on the development of 10B compounds, biological mechanisms, potential advantages, and clinical applications.
2.Influence of nonylphenol on cytoactive and the expression of G protein-coupled estrogen receptor in human colon cancer SW480 cells
Qingxu YANG ; Xiu LIU ; Tao ZHANG ; Weiwei NING ; Jie ZHANG ; Ming XIE
Chinese Journal of Digestive Surgery 2022;21(6):802-808
Objective:To investigate the influence of nonylphenol (NP) on cytoactive and the expression of G protein-coupled estrogen receptor 30 (GPR30) in human colon cancer SW480 cells.Methods:The experimental study was conducted. The human colon cancer SW480 cells were cultured in vitro. The influence of NP on proliferation, cell cycle, apoptosis and the expression of GPR30 in human colon cancer SW480 cells were analyzed by cell proliferation, cell cycle detection, cell apoptosis and gene expression and protein expression experiments. Cell grouping: SW480 cells cultured with medium were set as the control group, cultured with medium+1×10 ?8 mol/L estradiol were set as the estradiol group, cultured with medium+1×10 ?8 mol/L NP were set as the NP group, cultured with medium+1×10 ?8 mol/L NP+1×10 ?7 mol/L GPR30 specific antagonist G15 were set as the NP+G15 group, respectively. Observation indicators: (1) proliferation index of human colon cancer SW480 cells in the 4 groups; (2) cycle proportion of human colon cancer SW480 cells in the 4 groups; (3) apoptosis index of human colon cancer SW480 cells in the 4 groups; (4) GPR30 messenger RNA(mRNA) expression of human colon cancer SW480 cells in the 4 groups; (5) GPR30 protein expression of human colon cancer SW480 cells in the 4 groups. Measurement data with normal distribution were represented as Mean± SD and one way ANOVA was used for comparison between groups. The least significant difference method was used to test the pairwise comparison. Results:(1) Proliferation index of human colon cancer SW480 cells in the 4 groups. Results of the cell proliferation experiments showed that the proliferation indexes of human colon cancer SW480 cells in the control group, the estradiol group, the NP group and the NP+G15 group were 100.00±0.00, 89.19±4.86, 148.96±6.04 and 120.40±3.39, respectively, showing a significant difference among the 4 groups ( F=21.45, P<0.05). There was a significant difference between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the estradiol group, between the control group and the NP+G15 group ( P>0.05). (2) Cycle proportion of human colon cancer SW480 cells in the 4 groups. Results of the cell cycle detection experiments showed that the proportions of human colon cancer SW480 cells in the S phase of the cell cycles in the control group, the estradiol group, the NP group and the NP+G15 group were 39.96%±2.02%, 36.67%±0.62%, 43.85%±1.02% and 38.29%±1.42%, respectively, showing a significant difference among the 4 groups ( F=10.08, P<0.05). There were significant differences between the control group and the estradiol group, between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the NP+G15 group ( P>0.05). (3) Apoptosis index of human colon cancer SW480 cells in the 4 groups. Results of the cell apoptosis experiments showed that the apoptosis indexes of human colon cancer SW480 cells in the control group, the estradiol group, the NP group and the NP+G15 group were 1.67±0.18, 4.80±0.31, 0.75±0.11 and 2.20±0.19, respectively, showing a significant difference among the 4 groups ( F=136.79, P<0.05). There were significant differences between the control group and the estradiol group, between the control group and the NP group ( P<0.05), and there was no significant difference between the control group and the NP+G15 group ( P>0.05). (4) GPR30 mRNA expression of human colon cancer SW480 cells in the 4 groups. Results of quantitative real-time polymerase chain reaction detection showed that the relative expression rates of GPR30 mRNA in human colon cancer SW480 cells of the control group, the estradiol group, the NP group and the NP+G15 group were 1.00±0.00, 0.86±0.05, 1.89±0.27 and 0.64±0.12, respectively, showing a significant difference among the 4 groups ( F=26.61, P<0.05). There were significant differences between the control group and the NP group, between the control group and the NP+G15 group ( P<0.05), and there was no significant difference between the control group and the estradiol group ( P>0.05). (5) GPR30 protein expression human colon cancer SW480 cells in the 4 groups. Results of Western blot detection showed that the relative expression rates of GPR30 protein in human colon cancer SW480 cells of the control group, the estradiol group, the NP group and the NP+G15 group were 1.83±0.16, 1.68±0.15, 3.10±0.30 and 1.26±0.11, respectively, showing a significant difference among the 4 groups ( F=34.05, P<0.05). There were significant differences between the control group and the NP group, between the control group and the NP+G15 group ( P<0.05), and there was no significant difference between the control group and the estradiol group ( P>0.05). Conclusion:Low dose of NP can increase the proliferation index and the proportion of cells in the S phase of the cell cycles, decrease the apoptosis index, and promote the mRNA and protein expression of GPR30 in human colon cancer SW480 cells.
3.CT angiography in the evaluation of the risk of pulmonary embolism in patients with iliac vein compression syndrome and acute iliofemoral vein thrombosis
Zhanguo SUN ; Detao DING ; Qingxu LIU ; Yueqin CHEN ; Zhiying QI
Chinese Journal of Radiology 2021;55(11):1161-1166
Objective:To evaluate the risk and influencing factors of pulmonary embolism in patients with iliac vein compression syndrome (IVCS) and acute iliofemoral vein thrombosis by CT pulmonary angiography combined with CT venography of inferior vena cava.Methods:The data of 166 patients with acute left iliofemoral vein thrombosis diagnosed in the Affiliated Hospital of Jining Medical University from July 2016 to June 2020 were analyzed retrospectively. All patients underwent one-stop CT pulmonary angiography combined with inferior vena cava CT venography. The patients were divided into IVCS group (101 cases) and non-IVCS group (65 cases) according to the presence or absence of IVCS. The general data of the patients, the stenosis rate of left common iliac vein, the presence of inferior vena cava floating thrombosis, the presence of large pelvic collateral veins, the detection of pulmonary embolism and the pulmonary artery obstruction index of the two groups were compared, and multivariate logistic regression and multiple linear regression were used to analyze the influencing factors of the incidence and severity of pulmonary embolism in IVCS group.Results:There were significant differences in the stenosis rate of left common iliac vein [(68±8)% vs (25±14)%, t=-25.300, P<0.001], the incidence of inferior vena cava floating thrombosis [25/101, 31/65, χ2 =9.310, P=0.002], the length of inferior vena cava floating thrombosis [17.2 (10.9, 27.8)mm vs 27.4 (20.1, 55.9) mm, Z=-2.316, P=0.021], the incidence of pulmonary embolism (43/101 vs 41/65, χ2 =6.651, P=0.010) and the pulmonary artery obstruction index [(10.0% (5.0%, 17.5%) vs 22.5% (10.0%, 30.0%), Z=-3.490, P<0.001] between IVCS group and non-IVCS group. In the IVCS group, multiple logistic regression analysis revealed that the stenosis rate of left common iliac vein [β=-1.964, OR(95%CI) 0.140(0.031-0.638), P=0.011] and inferior vena cava floating thrombosis [β=1.212, OR(95%CI) 3.360(1.566-7.209), P=0.002] was independent factors for the occurrence of pulmonary embolism. Multiple linear regression showed that the influence of inferior vena cava floating thrombosis on the pulmonary artery obstruction index was statistically significant (b=0.352, t=2.410, P=0.021). Conclusion:The incidence and severity of pulmonary embolism in patients with IVCS and acute left iliofemoral vein thrombosis are lower than those without IVCS, and the presence or absence of inferior vena cava floating thrombosis is an important factor affecting the severity of pulmonary embolism.
4.Silencing lncRNA HOTTIP affects radiosensitivity of non-small cell lung cancer cell lines by up-regulating miR-663a
Shaoxian WEI ; Rui NIU ; Hailin YANG ; Xia LI ; Qingxu WANG ; Jun LIU ; Yongqiang HU
Chinese Journal of Radiation Oncology 2020;29(7):563-568
Objective:To investigate the effect of lncRNA HOTTIP on the radiosensitivity of four non-small cell lung cancer cell lines cultured in vitro by regulating the expression of miR-663a. Methods:Four non-small cell lung cancer cell lines (H838, H157, A549, and H1299) were irradiated with different radiation intensities (0, 2, 4, 6, and 8 Gy). Cell survival was detected by colony formation assay. The expression levels of HOTTIP and miR-663a were detected by qRT-PCR. A549 and H1299 cells were selected for the subsequent experiment. After silencing HOTTIP and/or over-expressing miR-663a, cell survival was detected by colony formation assay. Cell apoptosis was detected by flow cytometry. The expression levels of Cleaved caspase-3, Cleaved PARP andγ-H 2AX were quantitatively measured by Western blot. The targeting relationship between HOTTIP and miR-663a was vefiried by dual luciferase reporter assay and qRT-PCR. Results:The expression of HOTTIP was up-regulated, whereas that of miR-663a was down-regulated in the radiation-resistant H157, A549 and H1299 cells. Silencing HOTTIP or over-expressing miR-663a inhibited the survival of A549 and H1299 cells (radiosensitization ratios were 1.562 and 1.507, respectively), promoted the expression of Cleaved caspase-3, Cleaved PARP and γ-H 2AX, and accelerated cell apoptosis induced by radiation exposure. miR-663a was a target gene of HOTTIP, and HOTTIP negatively regulated the expression of miR-663a. The inhibition of miR-663a reversed the effect of silencing HOTTIP on the radiosensitivity of non-small cell lung cancer cells. Conclusion:Silencing HOTTIP can suppress the survival of non-small cell lung cancer cells and promotes cell apoptosis by up-regulating the expression of miR-663a, thereby enhancing the radiosensitivity of non-small cell lung cancer cell lines.
5.HPLC specific chromatograms of Xingnaojing injection.
Li-Xin YANG ; Wei-Hong FENG ; Bo-Hou XIA ; Li-Mei LIN ; Wei-Wei LIU ; Wan-Qing MIAO ; Guo-Feng GAN ; Ji-Gao ZOU ; Chun LI
China Journal of Chinese Materia Medica 2016;41(9):1640-1645
To establish and analyze the HPLC specific chromatograms of Xingnaojing injection manufactured by different factories. The separation was performed on a Thermo BDS Hypersil C₁₈ column (4.6 mm×250 mm, 5 μm), with the mobile phase consisting of acetonitrile-0.02% formic acid aqueous solution for gradient elution. The flow rate was 1.0 mL•min⁻¹, and the column temperature was 35 ℃. The detection wavelength was set at 254 nm, and the sample size was 20 μL. Eleven chromatographic peaks were identified as characteristic peaks of HPLC specific chromatograms of Xingnaojing injection, after analyzing 29 batches of Xingnaojing injection samples. Compared with the reference substances, seven of them were identified as eucarvone, camphor, curcumenone, curcumenol, curdione, curzerenone and germacrone, respectively. HPLC specific chromatograms of Xingnaojing injection manufactured by three factories could be easily classified into three categories after investigation with computer-aided similarity evaluation system combined with principal component analysis. The established HPLC specific chromatograms provide a basis for scientific evaluation and effective control of the quality of Xingnaojing injection.
6.Clinical significance of monitoring bone turnover markers changes before and after growth hormone treatment of prepubertal children with idiopathic short stature
Fei WANG ; Zhiying ZHU ; Qingxu LIU ; Jing XU ; Pin LI
Chinese Journal of Applied Clinical Pediatrics 2016;31(20):1541-1545
Objective To detect the levels and study the clinical significance of serum procollagen type Ⅰ amino-terminal propeptide (PINP) and β-C-telopeptides of type Ⅰ collagen (β-CTX) as bone turnover markers in recombinant human growth hormone (rhGH) treatment of prepuberty idiopathic short stature (ISS) children.Methods Forty patients of ISS (18 boys and 22 girls) had been collected and treated with GH 0.15 IU/(kg · d) injection every night.Serum levels of PINP,β-CTX,insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) were measured by electrochemiluminescence immunoassay in ISS before treatment and after 3,6 months,and they were also measured in 50 healthy children of the healthy control group,and the height,weight,body mass index,height standard difference score (HtSDS),bone age and growth rate were recorded.Results (1) In ISS group,the serum level of PINP[(479.51 ± 134.61) μg/L] was lower than that of the healthy control group [(651.31 ± 212.41) μg/L],the level of β-CTX[(0.84 ± 0.33) μg/L] was higher than that of the healthy control group [(0.50 ± 0.15) μg/L].The differences were statistically significant (t =2.276,-2.709,all P < 0.05).(2) The serum levels of PINP and β-CTX had no significant difference in 18 boys and 22 girls before and after GH treatment (P>0.05) of ISS.After 3 months of GH treatment,the serum levels of PINP[(736.15 ± 156.59) μg/L] and β-CTX [(1.08 ± 0.27) μg/L] were higher than those before treatment in 40 cases,and the difference was statistically significant (t =4.736,2.497,all P < 0.05),as the increase of PINP was particularly significant.HtSDS (-2.95 ±0.43),compared with before treatment (-2.69 ± 0.58),was significantly different (t =2.714,P < 0.05).However,after 6 months of GH treatment,the levels of PINP[(860.90 ±254.59) μg/L] and β-CTX[(0.94 ±0.32) μg/L] increased slowly (t =1.366,-0.831,all P > 0.05).HtSDS (-2.51 ± 0.54) showed no significant difference (t =1.609,P > 0.05) compared with 3 months of treatment.(3) The serum level of PINP was positively correlated with IGF-1 and IGFBP3 (r =0.636,0.673,all P < 0.05),and there was no correlation with β-CTX (r =0.336,P >0.05).PINP and β-CTX had significant correlation with HtSDS (r =0.655,0.782,all P < 0.05).Conclusions The serum PINP and β-CTX as bone turnover markers in serum can be used as one of the early supplementary indicators to predict GH response of ISS.
7.Progress in male sex determination and differentiation
International Journal of Pediatrics 2016;43(8):635-637
Sex determination and differentiation mean the process that the bipotential gonads develop into ovaries or testes.There are many genes involved in male(s) sex determination and differentiation.The changes of the regulating genes may lead to disorders of sex development.Sex-determining region Y (SRY) gene was the first discovered gene related to abnormal sexual development.Serval studies have found that SRY-related HMG box 9 (SOX9) and fibroblast growth factor 9 (FGF9) are associated with disorders of sex development in recent years.This article aims to provide an review of recent study of the role of SRY,SOX9 and FGF9 in sex determination and differentiation.It will provide a foundation for diagnosis and treatment of genetic disease related with male(s) sex determination and differentiation.
8.Expression and clinical significance of moesin and E-cadherin in invasive carcinoma of breast, no specific type
Xiaojuan PEI ; Xiufen XUE ; Yingling ZHU ; Shaojie LIU ; Anjia HAN ; Qingxu YANG
Chinese Journal of Pathology 2016;45(8):550-555
Objective To investigate the correlation of moesin and E-cadherin with biological behavior of breast cancer and its mechanism by comparing expression of moesin and E-cadherin in breast invasive carcinoma of no specific type (BIC-NST),breast ductal carcinoma in situ (BDCIS) and normal breast tissues adjacent to carcinoma.Methods Breast cancer cases of the Huizhou Municipal Center People Hospital were collected between Jan 2008 and Dec 2010,expression of moesin and E-cadherin in 104 cases of BIC-NST,84 cases of BDCIS and 53 cases of normal breast tissues adjacent to carcinoma were detected by tissue-microarray and SP immunohistochemical staining.Western blot was used to detect moesin expression of 16 BIC-NST fresh tissues.Results Expression rate of moesin in BIC-NST and BDCIS were significantly higher than normal tissues(P < 0.01),but the expression rate of E-cadherin in BIC-NST and BDCIS were significantly lower than those of normal tissues(P < 0.01).Expression rate of moesin in BIC-NST grade Ⅲ group was significantly higher than that of the grade Ⅰ group.There was a significantly positive correlation between histological grade and moesin expression(P < 0.05).However,E-cadherin expression rate in BICNST grade Ⅲ group was significantly lower than that in grade Ⅰ group,and there was a significantly negative correlation between histological grade and E-cadherin expression (P < 0.05).Moreover,no significant correlation was observed between moesin and E-cadherin expression in BDCIS tissues.Expression of moesin in clinical stage Ⅱ + Ⅲ BIC-NST was significantly higher than that in stage Ⅰ (P < 0.01).Expression of moesin was significantly associated with lymph node metastasis (P < 0.01).But no significant correlation was observed between moesin expression and age,tumor size and vascular invasion.However,expression of E-cadherin in clinical stage Ⅱ + Ⅲ BIC-NST was significantly lower than that in stage Ⅰ (P < 0.01).Expression of E-cadherin was significantly associated with lymph node metastasis and vascular invasion (P < 0.01).But no significant correlation was observed between E-cadherin expression,age and tumor size.There was a negative correlation between expression of moesin and E-cadherin in BIC-NST(P =0.021)and BDCIS(P =O.032).Conclusion Higher moesin and lower E-cadherin signal transduction is closely related to the recurrence and development of breast carcinoma,therefore moesin and E-cadherin might provide new targets for gene therapy in breast carcinoma.
9.Effect of intracavitary therapy on acute pulmonary embolism
Qingxu GUO ; Liguo YANG ; Yunlong LIU ; Chuang MA
Clinical Medicine of China 2014;30(2):180-182
Objective To explore the effect of intracavitary therapy on acute pulmonary embohsm.Methods Fifteen patients were selected as our subjects,who suffered acute pulmonary embolism and received percutaneous catheter thrombus crashing and catheter directed thrombolysis in Beijing Military.Region General Hospital from January 2009 to June 2011.Local injection of Urokinase was performed with a total amount of 500 000 U in catheter directed thrombolysis.After thrombolysis,low molecular Heparin was administered to patients for 7-10 days and oral administration of Warfarin was performed for 3-6 months.Clinical symptoms,improvement of physical signs,complications,changes of mean pulmonary arterial pressure(mPAP) and arterial partial pressure of oxygen(PO2),and the opening of pulmonary artery were recorded.Results The pulmonary arteries of the 12 patients were completely opened,and partially opened in 3 patients.The effective rate was 100% (15/15).mPAP was reduced from (40.07 ±5.97) mmHg to (20.00 ±4.66) mmHg (t =-1.128,P < 0.05),PO2 was increased from (50.26 ± 9.30) mmHg to (80.49 ± 9.04) mmHg (t =1.246,P < 0.05).Patients were followed-up for 3-6 months and no recurrence case was seen.Conclusion The interventional therapy is effective,safe and practicable in the treatment of acute pulmonary embolism.
10.Recombinant expression and biological activities of fusion protein EspA-Stx2B from enterohemorrhagic E. coil O157:H7
Qingxu WANG ; Xuhu MAO ; Yan PENG ; Yanqing LIU ; Shu YU ; Jianping CHENG ; Quanming ZOU
Chinese Journal of Microbiology and Immunology 2009;29(3):258-262
Objective To clone the gene encoding protein of EspA and Stx2B from EHEC OI57:H7 by DNA recombinant technology, construct prokaryotic expression vector pET-28a ( + )-espAstx2B, express fusion protein of EspA-Stx2B and to analyze the biological and immunological characteristics of the fusion protein. Methods the sequence encoding the protein of EspA and Stx2B was amplified by PCR from the enterohemorrhagic Escherichia coli strain. The amplified products were connected with linker by recombinant technology and cloned into pET-28a( + ) vector. The vector was then transferred to the host cells E. Coli BL21 strain (DE3). Following, the protein expression was induced by IPTG. The expression quantities and style of fusion protein was then determined by SDS-PAGE. Its immunoreactivity was analyzed by Western blot. Finally, BALB/c mice were injected with the preliminarily purified recombination protein EspA-Stx2B, then oral challenged these mice with EHEC O157-SMR2 and counteracted toxic substances with O157 ultrasonic supernatant. Results The determination of the sequence encoding of the espA-stx2B fusion gene has 100% of consistency with the sequence from GenBank Sakai strain and contrivable linker. This fusion protein EspA-Stx2B was expressed as inclusion body formation and the percentage is approximately 40%. Western blot suggested the fusion protein has excellent immunoreactivity. Titer of antiserum of the mice to EspA-Stx2B increased evidently. EspA-Stx2B could not decrease bacterial number attached to the intestinal tract of mice based on fecal shedding of Oi57 in mice. In the test of death of BAI,B/c causing by conteracting toxic substances with O157 ultrasonic supernatant, immunoprotection of EspA-Stx2B rate was 66.7%. Conclusion A recombinant plasmid that has high performance on expression of EspA-Stx2B prorein was successfully constructed in present study, and the fusion protein has excellent immunoreactivity and immunogenicity. EspA-Stx2B could not decrease bacteria] number attached to the intestinal tract of mice based on fecal shedding of O157 in mice, but evidently decrease the mortality rate of the mice. The antiEspA and anti-Stx2B had immunoprotection effect by different means. These results may provide the foundation for the further development on EHEC O157:H7 double subunit vaccine.

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