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.

Background and objective In the clinical treatment of patients with non-small cell lung cancer (NSCLC), the primary and acquired resistance of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) limits its clinical application, this need to explore new strategy or method to overcome this problem. Recently, some literatures have indicated that the antitumor role of heat shock protein 90 (HSP90) inhibitors by a variety of pathways may provide new strategy for resolving this problem. In this study, we examined the effect of 17-DMAG on NSCLC cell lines A549 and H1975 which were primary and acquired resistant to EGFR-TKI respectively, the purpose was to explore its inlfuence on cell prolifera-tion, apoptosis and the expression of EGFR in vitro as well as possible mechanism. Methods Atfer A549 and H1975 cell lines were treated with different concentrations of 17-DMAG respectively, the inhibitory rate of cell proliferation was measured by MTT assay in 24 h, 48 h and 72 h. We investigated the effect of 17-DMAG on the cell apoptosis with lfow cytometry and the ex-pression of HSP90 and EGFR with Western blot atfer treated with 17-DMAG for 48 h. Results Atfer treated with 17-DMAG, the inhibitory rate of different concentrations and time groups was signiifcant (P<0.01), and the effect was in time-and dose-dependent manner;the apoptosis rate of both two cell lines in all treated groups were signiifcantly higher than control group (P<0.01), and the effect was in dose-dependent manner. By Western blot analysis, there was no signiifcant difference between all treated groups and control group for the expression of both HSP90 and EGFR protein in A549 cell line and HSP90 protein in H1975 cell line atfer exposed to 17-DMAG for 48 h (P>0.05), while the difference was signiifcant for the expression of EGFR protein in H1975 cell line (P<0.01). Conclusion 17-DMAG inhibited the proliferation of NSCLC cell lines A549 and H1975 and also induced apoptosis of both cell lines. It down-regulated the expression of mutant EGFR protein while this phe-nomenon was not observed in EGFR-wild type cell line. hTis suggested that the mechanism maybe different between A549 and H1975 cell lines with different genetic backgroud. Our study provided new strategy for treatment with NSCLC being resistant to EGFR-TKI.

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.

China ; History, 20th Century ; Humans ; Portraits as Topic ; Zoology/history*

Objective:To evaluate the effect of unilateral pediatric kidney donation for adult kidney transplantation.Methods:Retrospective analysis was conducted on the cases of children who donated unilateral donor kidney for adult kidney transplantation recipients in our hospital, and those who were followed up for more than three years were included in this study. The body weight of the recipients in group A was ≤50 kg, and the body weight of the recipients in group B was ≤70 kg.The recipients were divided into 0-5 year old donor group (group A) and 6-17 year old donor group (B group). Clinical data, recipient/kidney survival, graft function and growth, and complications of the recipient were analyzed.Results:A total of 45 adult recipients were enrolled, including 12 in group A and 33 in group B. The renal survival rate at 3 years after operation was (100%, 96.9%)/(91.6%, 93.9%). One week after the operation, the early postoperative recovery of renal function in group B was better than that in group A, and the difference of serum creatinine was statistically significant ( P<0.05), while the difference of serum creatinine in other postoperative follow-up time points was not statistically significant ( P>0.05). Within a year, both groups of grafts continued to grow, reaching adult levels in one year. There was no statistical significance in the incidence of complications between the two groups ( P>0.05). The incidence of protein in the two groups was 33.3% and 6.1%, respectively, 1 case in each group still had proteinuria at 1 year after surgery, and only 1 case in the infant donor kidney recipient in group A had proteinuria at 3 years after surgery. Conclusions:Unilateral donor kidney transplantation from children can provide good results for adult patients with uremia by selecting suitable donors according to the weight of the recipient.

Objective:To explore whether hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) preconditioning can relieve inflammation, reduce cell apoptosis and alleviate renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly divided into three groups of sham operation (sham), ischemia reperfusion injury (IRI) and IRI+ HIF-PHI ( n=6 each). In IRI+ HIF-PHI group, mice received an intragastric dose of roxadustat (20 mg/kg) every other day one week before. After renal IRI modeling, serum creatinine (SCr) level was monitored and hematoxylin-eosin (HE) staining employed for observing the pathological changes of renal tissue and scoring injury degree. Apoptosis of renal tubular epithelial cells was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mRNA expressions of HIF-1α, TNF-α and IL-1β in renal tissues. Immunofluorescence and immunohistochemistry were employed for detecting the expressions of hypoxia-inducing factor 1α (HIF-1α), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results:As compared with IRI group, SCr level declined markedly in IRI+ HIF-PHI group ( P<0.01), renal tissue injury improved markedly, semi-quantitative score of renal tubule injury dropped ( P<0.01), apoptotic cells decreased ( P<0.01) and the expression levels of TNF-α and IL-1β declined ( P<0.05). Compared with sham group, the mRNA expression of HIF-1α was not significantly elevated in IRI group ( P>0.05). Immunofluorescence showed that the expression of HIF-1α in medulla of renal tissues was up-regulated in IRI group, but not markedly in cortex. While the mRNA expression of HIF-1α was markedly up-regulated after a pretreatment of HIF-PHI ( P<0.05), the expression spiked markedly in renal cortex, but was weaker in medulla than that in IRI group. Conclusions:HIF-PHI can boost the expression level of HIF-1α, reduce the expression of inflammatory factors, relieve the inflammatory response, reduce cell apoptosis, improve renal function and alleviate renal ischemia reperfusion injury.

Objective:To conduct a comparative analysis of the radiation damage to zebrafish embryos and the associated biological mechanism after ultra-high dose rate (FLASH) and conventional dose rate irradiation.Methods:Zebrafish embryos at 4 h post-fertilization were exposed to conventional and FLASH irradiation (9 MeV electron beam). The mortality and hatchability of zebrafish after radiation exposure were recorded. Larvae at 96 h post-irradiation underwent morphological scoring, testing of reactive oxygen species (ROS) levels, and analysis of changes in oxidative stress indicators.Results:Electron beam irradiation at doses of 2-12 Gy exerted subtle effects on the mortality and hatchability of zebrafish embryos. However, single high-dose irradiation (≥ 6 Gy) could lead to developmental malformation of larvae, with conventional irradiation showing the most significant effects ( t = 0.87-9.75, P < 0.05). In contrast, after FLASH irradiation (≥ 6 Gy), the ROS levels in zebrafish and its oxidative stress indicators including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were significantly reduced ( t = 0.42-15.19, P < 0.05). There was no statistically significant difference in ROS levels in incubating solutions after conventional and FLASH irradiation ( P > 0.05). Conclusions:Compared to conventional irradiation, FLASH irradiation can reduce radiation damage to zebrafish embryos, and this is in a dose-dependent manner. The two irradiation modes lead to different oxidative stress levels in zebrafish, which might be a significant factor in the reduction of radiation damage with FLASH irradiation.