Background and purpose: Primary liver cancer is the malignant tumor of liver cells or intrahepatic bile duct epithelium with familiar metastasis and postsurgical recurrence. The purpose of this study was to investigate the effects of miR-148a on the invasion and migration of hepatocellular carcinoma cells and the underlying mechanisms. Methods: The supernatant containing LV-miR-148a lentivirus particles was used to infect SMMC-7721 cells. The expression of miR-148a was determined by RT-PCR. Wound healing assay and transwell assay were performed to detect the effects of miR-148a on the invasion of hepatocellular carcinoma cells. Gelatin zymography assay was used to detect the effects of miR-148a on the enzyme activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The expression of MMP-2, MMP-9, E-cadherin and vimentin proteins was detected by Western blot assay. Results:RT-PCR showed the expression of miR-148a was upregulated in the infected SMMC-7721 cells. Transwell assay and wound healing assay showed ectopic expression of miR-148a suppressed cell migration and invasion abilities. miR-148a overexpression led to the decrease of the enzyme activities of MMP-2 and MMP-9 (P<0.05). Western blot assay showed that the protein expression of MMP-2, MMP-9 and vimentin proteins was signiifcantly decreased, the expression of E-cadherin had no changes. Conclusion:miR-148a is able to inhibit the migration and invasion of human SMMC-7721 cells in vitro, and the possible mechanisms may be related to decrease the enzyme activities of the MMP-2 and MMP-9 and the down regulation expression of MMP-2, MMP-9 and vimentin.

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.

Objective:To investigate the dosimetry advantage of 3D-printed minimally invasive guided template used in local advanced cervical cancer intracavitary combined with interstitial radiotherapy.Methods:A total of 68 cases with locally advanced cervical cancer who were admitted to Hebei Cangzhou Hospital of intergrated traditional Chinese medicine and western medicine from May 2016 to August 2019 were selected. All the patients had eccentric tumor or large tumor (tumor diameter >5 cm) after radiotherapy. Intensity modulated radiotherapy was used for external radiotherapy, and intracavitary combined with interstitial radiotherapy was used for brachytherapy. The prescription dose of high-risk clinical target volume (HR-CTV) is 6 Gy/fraction, once a week, five fractions in total. Sixty-eight patients were randomly divided into two groups, 35 cases in the template group who received minimally invasive 3D printing guided template assisted intrauterine tube implantation and insertion needle implantation, and 33 patients in the free implantation group who received free hand intrauterine tube implantation and insertion needle implantation. The position and depth of the insertion needle were adjusted by CT-guidance, and the final CT image was transmitted to the Oncentra Brachy treatment planning system, then the target volume and organs at risk were delineated for planning and treatment.Results:A total of 340 brchytherapy plans were made, including 175 in the template group and 165 in the free implantation group. The D90 values of the HR-CTV and intermediate-risk clinical target volume (IR-CTV) in the template group were increased ( t=3.63, 2.45, P<0.05), and D2 cm3 values (dose of 2 cm 3 of organ at risk) of bladder, rectum and sigmoid colon were significantly decreased ( t=-2.81, -2.54, -2.33, P<0.05). At the same time, the average CT scanning times of each treatment in the template group was (1.78±0.53) times, the average duration of each treatment was (11.35±3.98) min, and the average number of needles used in each implant treatment was (5.21±1.37). The result of free implantation group was higher than that of the template group. The differences were statistically significant ( t=-2.26, -4.53, -3.21, P<0.05). Conclusions:For localized advanced cervical cancer patients with eccentric or large tumors, the 3D printed minimally invasive guided template for intracavitary and interstitial implantation has obvious dosimetry advantages, and the operation is simpler and the duration is shorter.

Objective: To investigate the application of 3D-printed minimally-invasiveguided template in the treatment of recurrent cer-vical cancer after surgery, assisting interstitial brachytherapy. Methods: From July 2017 to April 2018, a total of 10 patients admitted to Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei province with recurrent cervical cancer after radi-cal surgery underwent the 3D-printed customized template-assisted interstitial brachytherapy. According to the specific conditions of patients, different vaginal localization templates were selected for CT simulation localization. The main guidance needle space distribu-tion was designed, and 3D minimally-invasive guidance templates were printed. Then, needles were inserted according to the main guide channel of the template commissioned by medical photosensitive resin. The high-risk clinical target volume (HR-CTV) of 6 Gy/fraction was administered (4 to 6 fractions). Results: Overall, 10 patients were treated with implantation for a total of 52 times. Treat-ment with average scanning CT number for each brachytherapy was (1.58±0.70) times. The average elapsed time for each brachythera-py implant treatment, from plug implant to inserting planting needle satisfactorily with the location of the tumor, was (10.88±2.94) minutes. The mean number of metal needles used was (5.69±1.91) in each brachytherapy. The mean D90 value for high-risk clinical tar-get volume (HR-CTV) was (6.41±0.29) Gy. The cumulative D2cm3 values for the bladder, rectum, and sigmoid colon were (4.75±0.37) Gy, (3.93±0.26) Gy, and (4.33±0.24) Gy, respectively. After 3 months of treatment, the efficacy was evaluated in 8 cases with CR and 2 cas-es with PR. Conclusions: The technology of 3D-printed minimally-invasive guided template shows the advantage of accurate location and superior repeatability in the application of interstitial brachytherapy in treating recurrent cervical cancer after operation, which in-volves less time and insertion needles. The patients had minor aches and few complications. The tumor shrank significantly, which indi-cated a bright future of the technology's clinical application.

Objective: To evaluate the efficacy and safety of bevacizumab in the treatment of radiation brain necrosis, and to provide guidance for rational clinical application. Methods: A retrospective analysis was made of 14 patients with radiation brain necrosis who had failed to receive mannitol and hormone treatment or had been treated for the first time. All the patients were divided into two groups according to different treatment regimens (5.0 mg/kg repeated every 14 d and 7.5 mg/kg repeated every 21 d). The changes of enhanced lesions in MRI T1W1 phase and edema in T2W1 phase were compared separately in the two groups. The clinical symptoms, changes of KPS score and adverse drug reactions were recorded. Results: Totally 14 patients completed at least two cycles of treatment. After two cycles of treatment, the KPS scores of both groups were improved. The KPS scores of 5.0 mg/kg group were increased by 31.66 points on average compared with those before treatment. The KPS scores of 7.5 mg/kg group were increased by 27.50 points on average compared with those before treatment. The volume of CRN lesions were decreased(46.0±9.4)%(t=6.57, P<0.05) and the volume of edema lesions decreased(68.9±8.9)%(t=3.32, P<0.05) in 5.0 mg/kg group. In 7.5 mg/kg group, these two parameters were reduced by(53.9±10.7)%(t=7.89, P<0.05 and (77.1±14.3)%(t=4.22, P<0.05), respectively. There was no significant difference in the reduction of the mean volume of CRN lesions and the volume of edema area between the two groups (P>0.05). In this study, the incidence of adverse events in the 5.0 mg/kg group was similar to that in the 7.5 mg/kg group, with no significant difference(P>0.05). Conclusions Bevacizumab can significantly improve the clinical symptoms and quality of life of patients with radiation brain necrosis. The safety of 5.0 mg/kg treatment regimen repeated every 14 d is similar to that of 7.5 mg/kg treatment regimen repeated every 21 d, which can be used for reference in the treatment of CRN.

OBJECTIVE: Acetaminophen (APAP) overdose is a common cause of liver injury. This study aimed to investigate the protective effect of honokiol (Hon) against APAP-induced hepatotoxicity and its potential mechanism. METHODS: C57BL/6 mice were administrated with Hon (10 and 30 mg/kg) after APAP (300 mg/kg) treatment. On 1.5 h and 5 h after Hon treatment, mice were sacrificed. Serum and liver were collected. And then, liver injury-related indexes, APAP metabolism-related indexes, mitochondrial respiratory chain function-related indexes, and mitochondrial membrane function-related protein expression were evaluated. RESULTS: It was found that Hon significantly decreased serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity and glutathione (GSH) depletion, increased hepatic catalase (CAT) and GSH peroxidase (GSH-Px) activities, reduced hepatic MDA and 3-nitrotyrosine contents, inhibited hepatic CYP1A2 activity and APAP protein adducts (APAP-CYS) formation. Meanwhile, oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV in mitochondrial respiratory chain was increased, whereas the release of H₂O₂ in the mitochondria was decreased following Hon treatment. Furthermore, Hon markedly down-regulated p-JNK in both cytosol and mitochondria, and obviously inhibited the release of apoptosis inducing factor (AIF) and endonuclease G (EndoG) from mitochondria to cytosol. CONCLUSION Hon alleviated APAP-induced liver injury through the following pathways: Reducing the production of APAP-CYS by inhibiting CYP1A2 activity; Ameliorating hepatic oxidative stress by increasing the levels of hepatic CAT, GSH-Px and GSH; Improving mitochondrial respiratory chain function by promoting oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV; Improving the function of mitochondrial membrane by inhibiting p-JNK and its translocation to mitochondria, thereby reducing the release of AIF and EndoG.