Objective To explore the effects of signaling pathways inducing activation of DC-SIGN promoter on the activity of HIV-1 5'LTR.Methods The sequences of DC-SIGN promoter and HIV-1 5'LTR were amplified by PCR and then cloned into pGL-3/Basic plasmid to constructluciferase reporter plasmids for DC-SIGN promoter and HIV-1 5'LTR.Differentiated THP-1 cells stimulated by PMA (phorbol myristate acetate) were used as the in vitro model of DCs.The activaties of DC-SIGN promoter and HIV-1 5'LTR induced by IL-4 in differentiated THP-1 cells were studied using luciferase reporter plasmids.The signaling pathways were identified by using specific inhibitors.Results IL-4 induced signaling pathways could increase the activities of HIV-1 5'LTR and DC-SIGN promoter for more than two times in THP-1 cells transfected with luciferase reporter plasmids.However,the activity of HIV-1 5'LTR was weaker than that of DCSIGN promoter.ERK/JAK-STAT/NF-κB signal pathway blockers could inhibit the luciferase activity driven by DC-SIGN promoter,of which ERKI/2 blocker showed the strongest inhibitory effect that almost completely blocked IL-4 induction.NF-κB blocker had a significant inhibitory effect on HIV-1 5'LTR activity at a rate of 52.32％,followed by the ERK blocker at a rate of 43.31％.Conclusion This study suggested that IL-4-induced signaling pathways mediate the activation of DC-SIGN promoter and HIV-1 5'LTR through NFκB and ERK.

OBJECTlVE To study the reIationship between microRNA(miRNA)-122 and Iiver injury in-duced by anti-tubercuIosis drugs,and to discover the new biomarkers for earIy diagnosis of this type of Iiver injury. METHODS mice were given 2 mL isoniazid oraIIy at 90 mg·kg-1 . BIood and Iiver tissue sampIes were coIIected at 1,3,5,7,14,21 and 28 d after administration of isoniazid. Serum gIutamic-pyruvic transaminase( GPT)and gIutamic-oxaIoacetic transaminase( GOT)IeveIs were determined using an automatic biochemicaI anaIyzer. Cu/ Zn-superoxide dismutase( Cu/ Zn-SOD ) activity and maIondiaIdehyde( mDA)content were detected by biochemicaI method. ReaI-time qPCR was used to measure the expression of miRNA-122. RESULTS GPT and GOT IeveIs were significantIy higher at 14 and 21 d(P﹤0.05)than in the controI. Cu/ Zn-SOD began to decIine whiIe mDA began to increase after 5 d(P﹤0.05). miRNA-122,which progressiveIy decreased after administration,was reduced to the mini-mum 0.58 ±0.02 at 14 d. There were good correIations between miRNA-122 and GPT,Cu/ Zn-SOD, mDA(the correIation coefficients were -0.370,0.268,and -0.298,respectiveIy),but no correIation with GOT was observed. CONCLUSlON The tissue miRNA-122 profiIe can be used as a sensitive marker for anti-tubercuIosis drug-induced Iiver injury,which couId contribute to the earIy diagnosis of Iiver injury.

Objective To compare the dosimetric differences between intracavitary brachytherapy in combination with interstitial brachytherapy or not for locally advanced cervical cancer.Methods From May 2016 to March 2017,35 patients with locally advanced cervical cancer treated with combined external beams and intracavitary/interstitial brachytherapy were selected in this study.The prescription of intensity-modulated radiation therapy was:46.8-50.4 Gy/26-28 fractions,1.8 Gy/fraction.The prescription for combined intracavitary/interstitial brachytherapy was 7 Gy/fraction × 4,once per week.Each patient was first implanted with a three tube applicator for brachytherapy,and the CT images were acquired for treatment planning.The three tube applicator was removed before a uterine tube and needles were implanted,thereafter planning images were acquired again.Dose to the targets and organs at risk were evaluated respectively for the two groups.Results A total of 212 brachytherapy plans were developed,including 106 intracavitary and 106 endoluminal combined interstitial plans.The target dose in endoluminal combined interstitial brachytherapy was significantly higher than that of intracavitary treatment alone,where D90 of the high-risk clinical target volume (CTV) and moderate CTV were both significantly increased (t =-6.01,-2.73,P ＜ 0.05).The D2 cm3 of the bladder,rectum and sigmoid colon were significantly reduced (t=3.07,4.52,2.91,P＜0.05).Conclusions The application of the endoluminal combined interstitial brachytherapy for locally advanced cervical cancer can significantly increase the target dose,and reduce the dose to organs at risk such as the bladder,rectum and sigmoid colon.