Objective To explore the inhibitory effects of sorafenib combined with cisplatin (DDP) on human hepatocellular carcinoma cells HepG2 in vitro, and the possible underlying mechanisms. Methods The HepG2 cells were divided to 4 groups as control group, sorafenib group, cisplatin group and sorafenib-cisplatin group. Sorafenib and cisplatin were used in single agent or in combination against HepG2 in vitro. The inhibitory effects of sorafenib and/or cisplatin on proliferation of HepG2 were determined by MTT assay at 24h, 48h, 72h and 96h after the addition of the drugs to HepG2 culture. Cell cycle at 24h time point and apoptosis at 48h time point were examined by flow cytometry (FCM). At 24h time point, cells were labeled by Rhodamine123 and mitochondrial transmembrane potential (??m) was determined by FCM, while caspase-3 activity was assessed by caspase-3 colorimetric assay. Results MTT assay showed that sorafenib and cisplatin, when used as a single agent or in combination, could inhibit the growth of HepG2 cells and induce apoptosis in vitro, while synergistic effect was noted when lower doses of sorafenib and DDP were used in combination. It was also found that combined use of sorafenib and cisplatin arrested HepG2 cells at G0/G1 and G2 phase as shown by cell cycle analysis, and the highest apoptosis rate appeared in sorafenib-cisplatin combination group (P

ObjectiveTo study the correlation between contrast-enhanced ultrasound (CEUS) features and Nottingham prognostic index (NPI) in patients with breast carcinoma. Methods The ultrasound features and microvascular imaging manifestation of 91 breast carcinomas confirmed by pathology were retrospectively analyzed.NPI was typically stratified into 3 major groups:NPI ＜ 3.4 ( n =19 ), NPI:3.4-5.4 ( n =52 ) and NPI ＞5.4(n =21 ). Results With the increase of NPI, the rate of heterogeneous enhancement, perfusion defects, edge enhancement higher than center enhancement, and unclear border increased.The difference among the 3 groups had statistical significance (P ＜ 0.05 ).There was no significant difference in enhancement order among the 3 groups ( P ＞ 0.05 ).The lesions of the 3 groups were mainly “high enhancement” and there was no significant difference among the 3 groups ( P ＞ 0.05 ).With the increase of NPI, the rate of early enhancement and late regression increased.The difference among the 3 groups had statistical significance ( P ＜ 0.05 ).With the increase of NPI, the rate of enlarged and twisted vessels as well as peripheral vessel burr increased.There was significant difference among the 3 groups ( P ＜ 0.05 ).ConclusionCEUS festures and microvescular architecture pattern of breast carcinoma are related to NPI, which is useful in predicating the prognosis of breast carcinoma.

Objective To investigate the clinical significance of IL-27 in hepatocellular carcinoma ( HCC) in the early stage , and to compare it with alpha-fetoprotein ( AFP) in diagnostic performance .Methods Enzyme-linked immunosorbent assay was used to detect the serum level of IL-27 in the HCC group and control group .Receiver operator characteristic ( ROC) curve was used to ana-lyze two indicators and the logistic regression model predicted value ( PRE) was obtained .Results The study indicated the concentra-tion of IL-27 in HCC group [(364.19 ±177.55)pg/ml] was significantly higher than the control group [(255.49 ±94.33)pg/ml], the area under the curve (AUC) of IL-27 and AFP were (0.804) and (0.818), respectively.Logistic regression obtained the regres-sion model PRE that contains AFP and IL-27, with a predicted area under the ROC curve for HCC (0.901), while the diagnostic sen-sitivity (84.8%) and specificity (96.7%) were significantly higher than the capability of individual diagnosis of each indicator .Con-clusions In this study we obtained the model which can be used for clinical diagnosis of hepatocellular carcinoma in future .

Objective To investigate the effect of whole-body irradiation with low-dose γ-rays on the central nervous system of mice.Methods Fifty C57 mice were randomly divided into 3 groups and treated with 0,0.5,1 Gy whole-body irradiation,respectively.24 or 48 h after irradiation,brain tissue of mice was resected and homogenated.The levels of amino acid neurotransmitter,including Glu,Asp,GABA and Gly in brain homogenate were measured by high performance liquid chromatography (HPLC).Results Compared to the brain tissue of untreated mice,the contents of Glu and Asp at 0.5 and 1 Gy (t=-4.080,-3.935,-4.416,-3.630,-4.831, - 4.656,P ＜0.05) in mice brain tissue significantly increased at 24 h at 1 Gy and 48 h.However,the contents of Glu and Asp had no obvious changes in mice brain tissue 24 h after 1 Gy of irradiation. The contents of GABA and Gly had no difference between irradiated groups and untreated control group. Conclusions Short-term whole-body irradiation with low-dose γ-rays induces slight stimulation effect on the central nervous system of mice.

Objective To investigate the effect of ionizing radiation on the invasion of the pulmonary adenocarcinoma cell line A549.Methods The invasiveness of A549 cells irradiated with 2 and 4 Gy doses of γ-rays was detected by using transwell invasion assay.The expression levels of matrix metalloproteinase (MMP)-2 mRNA and protein and phosphorylated signal transducers and activators of transcription 3 ( STAT3 ) protein were detected by reverse transcription PCR and Western blot.Results After irradiation with 2 or 4 Gy, the invasiveness of A549 cells increased by 200.0% ( F = 111.7, P ＜ 0.01 ) and 390.9% ( F = 593.7, P ＜ 0.01 ), respectively, compared with that in untreated A549 cells.Furthermore, the transcription and protein expression of MMP-2 24 h after irradiation and the phosphorylation of STAT3 12 h after irradiation were promoted.The irradiation-induced elevation of MMP-2 protein expression was suppressed using STAT3 phosphorylation specific inhibitor (AG490).Moreover,compared with 4 Gy of irradiation alone, treatment with 4 Gy of irradiation plus AG490 decreased the number of invasive cells by 76.1% ( F = 555.9, P ＜ 0.01 ), and the number of invasive cells in 4 Gy of irradiation plus AG490 group made up only 117.8% of that in untreated group ( F = 3.6, P ＞ 0.05 ).Conclusions Ionizing radiation could activate STAT3, which triggers the transcription of MMP-2, and then promote the invasiveness of A549 cells.

Objective To investigate the effects of signal transducer and activator of transcription 3 (STAT3) RNAi on the content of reactive oxygen species (ROS) and the DNA damage in glioma cells.Methods Glioma cells of the line U251 cells were cultured and transfected with STAT3 RNAi plasmid (pSilencer2.1-STAT3,STAT3 group) and pSilencer2.1-GFP (GFP control group) respectively.Part of the U251 cells were irradiated with γ-rays of 60Co as positive control group of smear phenomenon.The levels of ROS and malondialdehyde (MDA) in the cells were detected 24,48,and 72 h later by flow cytometry and fluorescence chamoluminescence analyzer,respectively.The DNA damage in the transfected U251 cells was examined by using single cell gel electrophoresis assay,and the cell cycle distribution was examined using FACS PI staining 12,24,and 36 h later.Results At 24 h after the transfection,the ROS level of the siSTAT3-transfected ceils was 8.91 times that of the control group (F = 89.296,P < 0.05),and returned to the normal level 48 h later.There were not significant differences in the MDA level of the cells 24,48,and 72 h later between the siSTAT3 group and siGFP group.Compared with the 8 Gy irradiation positive group with obvious smear phenomenon,smear phenomenon was shown in part of the ceils in the siSTAT3 group 6 h later,became less 12 h later,and disappeared completely 24 h later.Compared with the control group,lag of S stage rate was 17.22% and the lag of G2/M stage rate was 6.4% 12 h later in the siSTAT-transfected group,and the G0/G1 stage lag rate was 18.44% 24 h later,and the lag of S stage rate was 17.99% 36 h later.Conclusions Inhibition of STAT3 results in the change of oxidoreduction status in glioma cells,as well as damage and reparation of DNA.

Objective To assess the efficacy of gonadotropin-releasing hormone analogue(GnRHa)with or without recombinant human growth hormone(rhGH)treatment in Chinese short pubertal children with non-growth hormone deficiency.Methods Of 42 short pubertal children(14 males,28 females)without growth hormone deftcieney,the average age was(11.6±0.8)year.30 children were treated with slow release GnRHa with initial dose (100μg·kg-1·d-1,28d)and maintenance dose(60-80μg·kg-1·d-1,28d)labd rgGH with initial dose(0.15IU·kg-1·d-1)and maintenance dose(0.10-0.15IU·kg-1·d-1)for at least 1year.16 of them were still ongoing till the end of the second year.12 children were treated with GnRHa alone by initial dose(100μg·kg-1·d-1,28d)and maintenance dose (60-80μg·kg-1·d-1,28d),and 7 of them remained on it for 2 years.Dynamic changes including annual growth velocity(GV),bone age(BA)/chronologic age(CA)ratio,Tanner stage,height SDS for CA (HtSDSCA),height SDS for BA(HtSDSBA),and predicted adult height (PAHSDS)were observed.Results By the end of the first year tretment with combination therapy,the following parameters:GV,HtSDSCA,HtSDSBA,and PAHSDS all increased significantly(all P<0.05).Treatment with GnRHa alone did not yield significant changes in GV,HtSDSCA,HtSDSBA,and PAHSDS(all P>0.05).Changes in GV,HtSDSBA,and PAHSDS between these two groups were statistically significant(all P<0.05).By the end of the second year treatment,in the combination group,GV slowed from 6.7 to 5.5 cm/year(P<0.05).HtSDSCA,HtSDSBA,PAHSDS increased(all P<0.05).In the group with GnRHa treatment alone,GV slowed from 4.0 to 3.6 cm/year(P>0.05).HtSDSCA,HtSDSBA,PAHSDS increased(all P>0.05).Changes in GV,HtSDSCA,HtSDSBA,and PAHSDS between these 2 groups were statistically significant respectively(all P<0.05).Conclusion This combined treatment regimen significantly impreved the growth by increasing growth rate and delaying bone matumtion in pubertal chidren without growth hormone deficiency.Further study is needed to verify beneficial effects on the final height gain.

Objective To observe the final adult height (FAH) outcome and influencing factors in Turner′s Syndrome(TS) children treated with recombinant human growth hormone ( rhGH ).Methods Thirty TS children treated with rhGH were compared with 16 TS children without rhGH treatment and were followed up to achieve their FAH.Comparisons were made regarding predicted adult height (PAH),height standard deviation score for chronological age( HtSDScA ),height SDS for BA( HtSDSRA ),and growth velocity ( GV ) between rhGH treatment and without treatment groups and between the onset and by the end of rhGH treatment group.The factors determining FAH were also evaluated.Results FAH in rhGH treatment group was obviously improved as compared with untreatment group[ ( 149.5±6.3 vs 142.4±5.2) cm,P＜0.01 ].FAH in treatment group was positively correlated with height standard deviation score for chronological age ( Ht0 SDSCA ),Hto SDS for BA ( Hto SDSBA ),height age ( HA0 ) at preliminary diagnosis,and correlated with duration of rhGH therapy,duration of estrogen-free rhGH therapy,and PAH0SDS at preliminary diagnosis.Stepwise regression analysis indicated that duration of estrogen-free rhGH therapy and PAH0 SDS were the variables with the greatest identified influence on FAH (F =11.56 and F =86.91,P＜ 0.01 ).FAH in the 45,XO group was significantly different from the mosaicism group (45,XO/46,XX ) [ ( 147.2 ± 6.3 vs 153.3±6.4) cm,P =0.038].Conclusion rhGH treatment is efficacious in improving FAH of TS children,but a variability in the magnitude of the response to rhGH is recognized.Duration of estrogen-free rhGH therapy and PAH0SDS are the variables with the greatest identified influence on FAH,and karyotype may be one of the influence factors.rhGH treatment should be initiated as early as possible and sufficient course of estrogen-free rhGH therapy is needed to yield a satisfactory FAH.

Objective To assess the value of contrast-enhanced ultrasound (CEUS) in differential diagnosis of BI-RADS-US 4 breast lesions.Methods A total of 123 lesions underwent CEUS.The CEUS features of lesions were categorized into 5 malignant or benign indexes respectively,lesions displaying any two of the five features were diagnosed as malignant or benign.The diagnostic effect of CEUS for BI-RADS-US 4 lesion was analyzed according to the pathological results as the gold standard.Results CEUS of the 123 BI-RADS-US 4 breast lesions indicated that 75 lesions were malignant while 48 were benign.Pathological results confirmed that there were 72 malignant lesions and 51 benign.The proportions of malignant lesions in 4A category,4B category and 4C category were 16.2 ％,58.5 ％ and 93.3 ％ respectively.The accuracy,sensitivity,specificity,positive predictive value,and negative and positive predictive value of CEUS for the diagnosis of BI-RADS-US 4 lesions were calculated as 92.7％,95.8％,88.2％,92.0％ and 93.7 ％ respectively.Lesions showing false positive in CEUS mainly needed surgical treatment,such as fibroma with active growth mesen-chyme,intraductal papilloma and granulomatous mastitts.Conclusions Surgical treatment rather than aspiration biopsy are suggested for those diagnosed being malignant in CEUS of the BI-RADS-US-4 lesions,as they can be treated as BI-RADS5 lesions.Short-term visit or aspiration biopsy are suggested for BI-RADS-US-4 lesions diagnosed being benign in CEUS.

Objective To investigate the effect of ionizing radiation on the expression of transcription factor STAT3 target genes in the pulmonary adenocarcinoma cell line A549.Methods The expressions of VEGF,Bcl-2 and Survivin in A549 cells with or without STAT3 inhibition were detected by RT-PCR and/or Western blot 24 h after 2 or 4 Gy of γ-ray irradiation.Results After γ-ray irradiation with 2 or 4 Gy,the expression of VEGF and Survivin increased significantly.However,the expression of Bcl-2 was not affected by γ-ray irradiation.Furthermore,the increased expression of VEGF and Survivin induced by radiation was found to be inhibited after radiation-induced activation of STAT3 was blocked by AG490 inhibiter.Conclusions γ-ray irradiation could up-regulate the expression of Survivin and VEGF via activating STAT3.The increase of Survivin might partly inhibit the radiation-induced apoptosis of A549 cells,and the up-regulation of VEGF might contribute to the tumor angiogenesis.