Objective To evaluate the effect of bladder volume change on the doses to normal tissues in cervical cancer patients undergoing external three-dimensional conformal radiotherapy (3DRT)plus 3D conformal brachytherapy (3DCBT).Methods The study included 56 patients with cervical cancer who were admitted to our hospital from 2012 to 2013 and received radical external 3DRT and 3DCBT.During 3DCBT,the doses to 0.1,1.0,and 2.0 cm3(D0.1 cm3,D1.0cm3,and D2.0cm3,respectively) for the rectum,small intestine,sigmoid colon,and bladder under different bladder filling status (empty,50,100,and 150 ml) were compared and analyzed by paired t-test.Results The rectum D0.1cm3 with bladder volumes of 50and 100 ml were significantly reduced compared with that with an empty bladder (P =0.000,0.000).The D0.1 cm3,D1.0cm3,and D2.0cm3 for the small intestine with bladder volumes of 50,100,and 150 ml were significantly reduced compared with those with an empty bladder (P =0.008,0.000,0.000 and 0.000,0.000,0.000 or 0.000,0.000,0.000).The D0.1 cm3,D1.0cm3,and D2.0cm3 for the bladder with bladder volumes of 100 and 150 ml were significantly increased compared with those with an empty bladder (P =0.000,0.000 and 0.000,0.000 or 0.000,0.000).Conclusions The doses to the bladder and small intestine are influenced by different bladder filling status,but the doses to the rectum and sigmoid colon show no significant variation.The increase in bladder volume is helpful in reducing the dose to the small intestine.Without any change in the bladder dose,the bladder volume of 50 ml is more beneficial to reduce the dose to the small intestine than those of 100 and 150 ml.

Objective To investigate the correlation between ICRU reference point dose and dosevolume parameters of organs at risk (OARs) under different bladder and rectal filling status in threedimensional conformal brachytherapy for locally advanced cervical cancer.Methods A total of 31 patients who received magnetic resonance imaging-guided three-dimensional conformal brachytherapy for cervical cancer in 96 fractions were enrolled.The ICRU rectal and bladder reference points were determined in the treatment planning system,and the doses at these points were recorded and compared with the dose-volume parameters of the rectum and bladder.The paired t-test was used to analyze the differences between them.Results Bladder DICRU was lower than bladder D0.1cm3 and D1 cm3 (P=0.000 and 0.000),higher than bladder D5 cm3 and D10cm3 (P=0.000 and 0.000),and similar to bladder D2 cm3 (P=0.345).Under the bladder filling status,bladder DICRU was lower than D2cm3.Rectal DICRU was lower than rectal D0.1 cm3 and D1cm3 (P =0.000 and 0.002),higher than rectal D5 cm3 and D 10 cm3 (P =0.000 and 0.000),and similar to rectal D2cm3 (P=0.058).The ICRU bladder and rectal reference point doses were positively correlated with corresponding D2 cm3.In the case of bladder volume ≥ 200 cm3,the ICRU bladder reference point dose underestimated bladder D2 cm3.In the case of rectal volume ≥ 37 cm3,the ICRU rectal reference point dose overestimated rectal D2 cm3.Conclusions In three-dimensional conformal brachytherapy,it is generally safe to use D2 cm3 as an index to evaluate OARs,but when the bladder or rectum is in an empty status,the ICRU bladder or rectal reference point doses should be considered.

Objective To investigate the dosimetric differences between Utrecht applicator and ring applicator in three-dimensional (3D) conformal brachytherapy for locally advanced cervical cancer.Methods Twenty-five patients with locally advanced cervical cancer were treated with magnetic resonance imaging-guided 3D conformal brachytherapy.Utrecht applicator and ring applicator were used interchangeably for 96 cycles.Patients were divided into two groups according to the type of applicator.Each group received 48 cycles of treatment, in which ring applicator was first applied for 26 cycles and Utrecht applicator was first applied for 22 cycles.High-risk clinical target volume ( HR-CTV) , width, thickness, and D90 at the point A level, D2 cm3 of organs at risk (OARs), V7 Gy , W7 Gy,A, V7 Gy ,A, and W/T7 Gy were evaluated and analyzed using paired t-test.Results There were no significant differences in HR-CTV and the width, thickness, and D90 at the point A level between the Utrecht group and the ring group ( P=0.487;P=0.340;P=0.857;P=0.921);there were no significant differences in D2 cm3 values of bladder, rectum, sigmoid, and bowel between the two groups ( P=0.136;P=0.802;P=0.985;P=0.458);there were no significant differences in V7 Gy and T7 Gy,A between the two groups ( P=0.076;P=0.435) .The Utrecht group had a significantly larger W/T7 Gy,A than the ring group ( P=0.002 ) .Conclusions Utrecht applicator is appropriate for patients with relatively large width and width/thickness ratio of HR-CTV at the point A level.

Objective To explore the correlation between the dose measured in the rectum and reference dose in three?dimensional brachytherapy ( 3DBT ) for cervical cancer, and to evaluate the significance of the dose measured in the rectum. Methods Fifty patients receiving radiotherapy for cervical cancer were selected, and 3DBT was performed after pelvic external beam radiotherapy. According to the rectal monitoring method recommended in the report ICRU38, in vivo monitoring was applied to obtain the dose measured in the rectum, reference point dose ( DICRU ) , and D2 cm3 , and the planned dose was obtained from the planning system. The differences in these values were determined by the paired t?test and correlation analysis was performed with Pearson test. Results The dose measured in the rectum was higher than the planned dose (3. 48 vs. 3. 25,P=0. 000), and lower than DICRU(3. 48 vs. 3. 71,P=0. 000) and D2 cm3(3. 48 vs. 3. 87,P=0. 002). A linear relationship existed between the dose measured in the rectum and the planned dose, with a deviation percentage of-20% to 40% and an average deviation of 8. 16%;63%of the patients with cervical cancer had a deviation of<± 10%;the maximum deviation was 60%. The dose measured in the rectum had a strong correlation with DICRU(r=0. 722), but a weak correlation with D2 cm3 ( r=0. 284) . Conclusions During 3DBT for cervical cancer, the dose measured in the rectum has certain deviations, but has a linear correlation with the planned dose. Both the dose measured and the planned dose underestimate the dose at the reference point in the rectum, and in vivo rectal monitoring may be an effective method for quality control.

Objective To investigate the clinical application of Utrecht applicator in three-dimensional image-guided brachytherapy (3D-IGBT) for locally advanced cervical cancer,as well as its application discipline in intracavitary/interstitial (IC/IS) therapy.Methods A retrospective analysis was performed for the clinical data of 45 patients with locally advanced cervical cancer who received radical radiotherapy,and the patients received external beam radiotherapy followed by 3D-IGBT.A total of 130 times (n =45) of IC/IS therapy were performed,and the patients who received such therapy were all enrolled.The patients who met the target dose fractionation defined in the plan were enrolled as group A (n=37,86 times),and the other patients were enrolled as group B (n=22,44 times).Two groups difference was analyzed with Group t-test.Results The frequencies of use of 15-,20-,and 25-mm ovoids by the applicator were 50.0％,20.0％,and 30.0％,respectively,and the 30-mm ovoid was not used.A total of 499 needles were used,and the frequencies of use of 6,7,10,and 11 insertion holes were 23.1％,21.2％,21.2％,and 24.1 ％,respectively.Group A had a significantly lower mean number of the needles than group B (3.7 vs.4.2,P=0.008).Compared with group B,group A had a significantly lower mean high-risk clinical target volume (CTV)(40.71±18.43 cm3 vs.51.81±14.74 cm3,P=0.001),as well significantly lower width and height of high-risk CTV (P=0.011 and 0.006),but the thickness of high-risk CTV was similar between the two groups (P=0.595).The difference between height and insertion depth (DH) was similar between the two groups (P=0.366).Group A had a smaller difference between width and pinhole distance Dw than group B (P=0.007).Conclusions When IC/IS therapy is performed for locally advanced cervical cancer,the 15-,20-,and 25-mm ovoids of Utrecht applicator and 6,7,10,and 11 insertion holes are frequently used.When the number of needles is no less than 4 and the depth is no less than 3 cm,width is the major factor which affects the planned dose.

Objective To explore the dosimetric advantages of computed tomography-based and ultrasound-guided three-dimensional image-quided brachytherapy (3D-IGBT) combined with intracavitary/interstitial (IC/IS) brachytherapy for locally advanced cervical cancer.Methods A total of 45 patients with FIGO (2009) stage ⅠB2-ⅣA locally advanced cervical cancer who received radical external beam radiotherapy and 3D-IGBT combined with IC/IS brachytherapy in our hospital from 2013 to 2014 were analyzed.After the treatment with 192Ir-based IC/IS brachytherapy,patients had needles removed from the original images and received treatment only from IC radiation sources.Dosimetric differences in the planning D90 for high-risk clinical target volume (HR-CTV),D90 for intermediate-risk CTV (IR-CTV),and D2 cm3 for the bladder,rectum,sigmoid colon,and small intestines were determined and analyzed by paired t-test.Results A total of 260 after-loading treatment plans,including IC/IS treatment plans for 130 patients and IC treatment plans for 130 patients,were made.The D90 for HR-CTV and D90 for IR-CTV in the IC/IS brachytherapy group were significantly higher than those in the IC brachytherapy group (P =0.000;P =0.000).Moreover,the average D2cm3 values for the bladder and rectum were significantly reduced in the IC/IS brachytherapy group compared with those in the IC brachytherapy group (P =0.000;P =0.006).Conclusions The 3D-IGBT combined with IC/IS brachytherapy not only achieves a higher dose for the target volume,but also reduces the radiation dose to the bladder and rectum in the treatment of locally advanced cervical cancer.

Objective To compare target volume and dosimetry between computed tomography (CT)?and magnetic resonance imaging (MRI)?guided three?dimensional (3D) conformal brachytherapy for locally advanced cervical cancer, and to provide evidence for optimization of the image?guided approach and improvement of treatment regimen. Methods Thirteen patients with locally advanced cervical cancer who were treated with radical radiotherapy in our hospital in 2014 were enrolled as subjects. All patients received MRI?guided 3D conformal intracavitary/ interstitial brachytherapy. All patients received MRI and CT scans for each brachytherapy fraction, based on which the target volume delineation, intracavitary/ interstitial regimen design, and intracavitary?only treatment regimen design were performed. Comparison of data between MRI and CT scans was performed using paired t test. Results The width and volume of the high?risk clinical target volume ( HR?CTV) were significantly smaller in the MRI simulation than in the CT simulation ((38.0±9?? 4) mm vs. (45.1±8?? 7) mm, P= 0?? 000;(34.2±15?? 3) cm3 vs. (42.9±20?? 4) cm3 , P= 0?? 002), and the width, thickness, and volume of the intermediate?risk clinical target volume (IR?CTV) were also significantly smaller in the MRI simulation than in the CT simulation ((58.8±9?? 4) mm vs. (65.4±10?? 3) mm, P= 0?? 000;(34.8±6?? 3) mm vs. (37.5±6?? 3) mm, P= 0?? 001;(90.9±28?? 5) cm3 vs. (109.0±36?? 4) cm3 , P= 0?? 000). The D90 values for HR?CTV and IR?CTV were significantly higher in the MRI simulation than in the CT simulation (87?? 6 Gy vs. 85?? 8 Gy, P= 0?? 013;67?? 7 Gy vs. 66?? 3 Gy, P= 0?? 005), while the average D2 cm3 values for the bladder and rectum were significantly lower in the MRI simulation than in the CT simulation ( 73?? 1 Gy vs . 75?? 5 Gy , P= 0?? 011 ; 61?? 0 Gy vs . 65?? 7 Gy , P= 0?? 000 ) . Conclusions Compared with the MRI simulation, the CT simulation overestimates the width of target volume. MRI has substantial advantages in dosimetry for target volume and normal tissues. The intracavitary/ interstitial treatment can make up the reduced dose for the target volume resulting from the CT simulation.

Objective To study the activation of Janus protein tyrosine kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and its inhibitor-signal transducer and activator of transcription-1(SOCS-1) in patients with systemic lupus erythematosus. Methods A total of 45 patients with active systemic lupus erythematosus (SLE) and 30 healthy controls were randomly selected. Western blot was performed to measure the expression of Stat1 protein and phospho-Stat1 protein (an activated form of Stat1 protein) in the monocytes after stimulation with recombinant high mobility group box1 (rHMGB1) at various time points. Expression of Stat1 protein in the skin or lesional skin was also detected. Phasic expressions of SOCS-1 mRNA in the monocytes after rHMGB1 stimulation were detected by real-time reverse transcription-polymerase chain reaction. SOCS-1 gene expression in the skin or lesional skin was also detected. Results The expression level of Stat1 proteins in the monocytes from patients with SLE was higher than that from healthy controls (t=9.16,P＜0.01) and positively correlated with SLE disease activity index (SLEDAI) (r=0.59,P＜0.01). Expression of phospho-Stat1 in the monocytes from SLE patients was time-dependently upregulated after stimulation with rHMGB1 at various time points, while expression of SOCS-1 mRNA remained unchanged(all P＞0.05). Expressions of phospho-Stat1 protein and SOCS-1 mRNA in the monocytes from healthy controls were increased transiently after stimulation with rHMGB1(all P＜0.05). Both expressions of phospho-Stat1 protein and SOCS-1 gene in the lesional skin from patients with SLE were upregulated compared with those in normal skin from healthy controls (all P＜0.01). Conclusion There are hyperactivation of JAK-STAT1 signaling pathway and negative feedback down-regulation of SOCS-1 in patients with systemic lupus erythematosus. HMGB-1 may be partly involved in the pathogenesis of SLE by the abnormal mediating function of JAK-STAT1 signal transduction pathway.

Objective To evaluate therapeutic effects and complications of concurrent three-dimensional conformal radiotherapy (3DCRT) and chemotherapy in patients with limited-stage small cell lung cancer (LSCLC).Methods From June 2000 to August 2005, 93 histologically proved LSCLC patients were randomized into two groups:3DCRT group (n =46) and conventional group (n =47).In both groups, patients received one cycle chemotherapy, followed by concurrent chemoradiotherapy and then received consolidate chemotherapy.Chemotherapy was four to six cycles of PE regimen.Conventional irradiation field was setup in conventional group, while in 3 DCRT group clinical target volume (CTV) only involved visible tumor and adjacent lymphatic region.Radiotherapy was delivered at 2 Gy per fraction, 5 fractions per week to a median total dose of 60 -64 Gy.Those who achieved a complete response were treated with prophylactic cranial irradiation (PCI) with 30 Gy in 10 fractions.Results The follow-up rate was 100% in both groups.The number of patients completed 1-, 2-and 3-year follow-up were 36, 34 and 16 in 3DCRT group, 14, 7 and 8 in conventional group, respectively.The complete and overall response rate were 52% and 89% in 3DCRT group, while 47% and 85% in conventional group, respectively.The 1-, 2-and 3-year survival rates were 78%, 35% and 15% in 3DCRT group, 72%, 30% and 17% in conventional group, respectively.The median survival time was 23.2 and 22.8 months, respectively.There was no statistical difference in short-term (Χ~2 = 0.34 ,P = O.759) and long-term outcomes (Χ~2 = 0.18 ,P = 0.92).In 3DCRT group, the incidence of grade 1 +2 acute radiation pneumonitis and esophagitis, grade 1 +2 and grade 3 chronic radiation pneumonitis were lower than those in conventional group.There was no grade 3 or 4 acute radiation pneumonitis or esophagitis, or grade 4 chronic radiation pneumonitis in both groups.There was no difference in grade 1 + 2, grade 3 or grade 4 acute myelo-suppression between the two groups.Conclusions In the treatment of LSCLC, concurrent 3DCRT and chemotherapy can achieve satisfactory short-term and long-term outcomes with acceptable complications.

Objective: To observe the morphologic changes of pituitary adrenocorticotrophic hormone (ACTH) cells in Wistar rats at different altitudes, and clarify the mechanism of stress reaction to hypoxia in ACTH cells. Methods: Wistar rats were divided into three groups and moved to different altitudes (1700 m, 3100 m, 4050 m). After 12 days, changes of ACTH cells were observed by using immunohistochemisty, image analysis and electron microscopy. Results:The ratio (R) of immunoreactive cell area to scanned area and mean optical density (A) increased at higher altitude with statistically different R values between groups of 1700 m and 4050 m (P