Objective To investigate the regulation of melatonin (MT) on Toll-like receptor 4 (TLR4) signaling in diabetic db/db mice kidneys.Methods The 48 10-week-old male db/db mice were randomly divided into db/db group,db/db+MT 50 μg/kg group,db/db+MT 100 μg/kg group and db/db+MT 200 μg/kg group,each consisting of 12 mice.These mice received i.p.injections of MT These mice received i.p.injections of MT [dissoved in phosphate buffer solution (PBS)/ dimethylsulfoxide (DMSO) solution,given every day].Alternatively,12 db/m mice served as the control group.db/m and db/db group were injected i.p.with the same volume of PBS/DMSO solution.The animals were sacrificed after 12 weeks of dosage administration.Blood glucose (BG),body weight (BW),kidney weight (KW) and 24 h urinary albumin excretion rate (UAER) were determined;Kidney pathological lesions were evaluated by renal pathological staining.Immunohistochemistry of renal TLR4,NF-κB p65,and ED-1 was performed to determine the immunoreactivity.Western blotting was used to detect the expression of renal TLR4,myeloid differentiation factor 88 (MyD88),TIR-domaincontaining adaptor inducing interferon-β (TRIF),interferon regulatory factor 3 (IRF-3) and NF-κB p65,while the mRNA expressions of renal tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were evaluated by real-time PCR.Results Compared with control group,the levels of BG,BW,KW and UAER were much higher in db/db mice group (P ＜ 0.01),while KW in db/db+MT (100,200 μg/kg) groups and UAER level in db/db+MT (50,100,200 μg/kg) groups were distinctly decreased compared with those in db/db group (P ＜ 0.01).In week 12 db/db mice,the glomerular mesangial expansion index and tubulointerstitial injury index were increased compared with those in db/m mice (P ＜ 0.01).The above kidney histopathologic lesions were distinctly ameliorated by 50,100,200 μg/kg MT (P ＜ 0.05).Immunohistochemistry intensity of renal TLR4,NF-κB p65 and ED-1 displayed obvious differences between db/m mice and db/db mice (P ＜ 0.01),and that were remarkably decreased in db/db+MT (50,100,200 μg/kg) mice compared with db/db mice (P ＜ 0.05).Western blotting showed that the protein expression of renal TLR4,MyD88,TRIF,IRF-3 and NF-κB p65 were stronger in db/db group compared with those in db/m group (P ＜ 0.05) and weaker in db/db+ MT (50,100,200 μg/kg) groups compared with those in db/db group (P ＜ 0.05).Futhermore,the mRNA expressions of renal MCP-1 and TNF-α were higher in db/db group compared with those in db/m group (P ＜ 0.01) and lower in db/db+MT (50,100,200 μg/kg) groups compared with those in db/db group (P ＜ 0.01).Conclusion Melatonin may partly down-regulate TLR4 signaling pathway to inhibit Inflammatory reaction and alleviate kidney injury in diabetic db/db mice.

Objective To summarize the experience in the diagnosis and treatment of intraductal papillary mucinous neoplasms (IPMN) of the pancreas.Methods The clinical data of 16 cases of intraductal papillary mucinous neoplasms of the pancreas in the First Affiliated Hospital of China Medical University from January,2000 to October,2013 was retrospectively analyzed.Results There were 9 males and 7 females,age ranging from 37 to 61 years (average 49 years).The common complaint was epigastric pain.Ultrasonography and CT scan found solid lesions in all cases,main pancreatic duct dilatation was found in 10 cases.All the cases received surgical resection of the tumor.Pathology showed adenomas in 14 cases,borderline tumors in one,and adenocarcinoma in one.14 patients were followed-up ranging from 5 to 48 months,all were alive without recurrence and metastasis.Conclusions IPMT is a special type of pancreatic tumor.Surgical resection is the most effective treatment with excellent prognosis.

OBJECTIVE To investigate the possible effects of meteorological and environmental factors on IL-4 gene specific DNA methylation levels in CD4+T cells of children with AR.METHODS Thirty five pediatric AR patients(6-12 years) followed up for one year from the Department of Otolaryngology, Shanghai Children Medical Center from Jan, 1, 2012 to Dec. 31, 2012 were included in this study. Data on daily particulate matter of diameter smaller than 10 micrometer(PM10) and particulate matter of diameter smaller than 2.5 micrometer(PM2.5) was available as average values derived from the data of 6 state-controlled monitoring stations distributed across Pudong District, Shanghai. We quantified IL-4(interleukin-4) gene specific DNA methylation levels in CD4+T cells from 35 patients with AR and 30 healthy controls. mRNA levels of IL-4 gene were measured by real-time reverse transcriptase-PCR. Methods of personal exposure assessment of PM2.5 and PM10 were measured.RESULTS Compared with controls, IL-4 promoter region was hypomethylated in AR CD4+T cells(P=0.038). Of all observed CpG sites in IL-4 promoter region, there was significant differences in CpG-48, CpG+54(P=0.041, 0.032). IL-4 mRNA expression was significantly increased in CD4+T cells(P=0.039). The level of IL-4 mRNA expression was negatively correlated to the mean level of methylation in IL-4 promoter region. After adjusting, level of PM10 exposure was negatively correlated with level of methylation in IL-4 promoter region(r2=0.419,β=-0.470,SD=0.781,P=0.045). CONCLUSION Level of methylation in IL-4 promoter region may be affected by PM10 exposure.

Objective To compare the dose distribution of postoperative plans with preoperative plans for 3D printing guide template assist radioactive seeds implantations,and explore the accuracy of treatment at dosimetry level.Methods A total of fourteen patients registered from Dec 2015 to Mar 2016 who were applied with 3D printing guide template assisted radioactive seed implantations in the hospital were included in this study.The preoperative planning design and 3D printing template production were performed for all patients.The dose related parameters including D90％,minimum peripheral dose (MPD),V100％,V150％,V200％,conformal index (CI),external index (EI),and homogeneity index (HI) were compared between pre-and post-operation.The paired t-test was used to perform the statistical analysis.Results A total of fourteen 3D printing individual templates were produced which included 16 treatment areas.Compared with preoperative plans,the mean value of V100％,Dg0％ and V150％ decreased while the mean value of V200％ and MPD increased in postoperative plans.However,there was no significant difference between the two groups except for V100％ (t =2.451,P ＜0.05).The differences of CI,EI,HI between two groups were not statistically significant (P ＞ 0.05).Conclusions The validation of actual dose distribution in postoperation assistied by 3D printing template in seed implantation shows that most of parameters could meet the expectation of preoperative plans,which indicates the improvement in accuracy for this new type of treatment.

Objective To compare the pre-and post-operative tumor target volume and to examine the consistency in physical dosimetric parameters of organs at risk (OAR) following 3D-printed coplanar template (3D-PCT)-assisted and CT-guided radioactive seed implantation.Methods The 3D-printed coplanar template was designed using a computer software, and the coordinate system was established where the center was used as the basis for setting the x axis and y axis.Crosses defining the center of treatment were drawn on the patient''s body and matched with the corresponding central point, x axis, and y axis of the coplanar template.3D-PCT-assisted and CT-guided radioactive seed implantation was performed based on the pre-operative plan, and the pre-operative, operative, and post-operative plans were designed to evaluate the target tumor volume and the normal dose received by the tissues.In addition, dosimetric parameters, including D90(minimum dose received by 90% of the gross target volume), V100, V150, V200(percentage of GTV that received 100%, 150%, and 200% of the prescribed dose, respectively), minimum peripheral dose (MPD), conformal index (CI), external index (EI), and homogeneity index (HI) in the pre-operative and post-operative plans were also assessed and compared using the Wilcoxon test. Results Fourteen patients treated in our institution from August to October, 2016 were included in this study. The median age of the patients was 61.5 years, and the median Karnofsky Performance Scale score was 80. A total of 14 lesions from the 14 patients were treated by seed implantation in the neck (n=4), chest (n=3), abdomen (n=5), and pelvis (n=2). Of the 14 patients that underwent implantation, 8 had previously received radiation therapy, and 6 had not received radiation therapy. Dosage optimization was performed for all patients during the operation. The median activity of the implanted seeds was 0.625 mCi (0.55-0.75 mCi,1 Ci=3.7×1010 Bq), and the preoperatively planned median number of needling and implanted seeds were 9(4-34) and 45.5(10-162), respectively. However, the actual median number of needling and implanted seeds were 9.5(4-34) and 45.5(10-162), respectively. Dosimetric analysis showed that there were no significant changes in tumor volume (P=0.135), D90(P=0.208), MPD (P=0.104), V100(P=0.542), V150(P=0.754), V200(P=0.583), CI (P=0.426), EI (P=0.326), and HI (P=0.952) after implantation. Conclusions 3D-PCT guidance and dosage optimization can result in good consistency between pre-and post-operative plans for radioactive seed implantation. 3D-PCT is a convenient and cheap technique suitable for large-scale clinical application.

Objective:To verify the accuracy and feasibility of radioactive 125I seed implantation assisted by an optical navigation system and a 3D-printing non-coplanar template in the treatment of recurrent head and neck cancers. Methods:A total of 12 patients with recurrent head and neck cancer treated with radioactive 125I seed implantation assisted by an optical navigation system and 3D-printing non-coplanar template were enrolled from Dec 2018 to Dec 2019.The pre-plan and post-implant implantation needle number and implanted seed number were recorded.Meanwhile, their dosimetric parameters were compared, including D90, minimum peripheral dose (MPD), V100, V150, V200, conformity index (CI), external index (EI), and the homogeneity index (HI) of the target volume. Results:The median lesion volume was 31.5 cm 3, the median number of seeds was 61.5, and the median prescription dose was 130 Gy.The means of the pre-plan D90, MPD, V100, V150 and V200 were 134.2, 64.6, 93.3, 75.3 and 39.3 Gy, respectively, while those of post-implant D90, MPD, V100, V150, and V200 were 146.7, 68.94, 97.47, 80.40 and 48.30 Gy, respectively, with no statistically significant difference ( P>0.05). Meanwhile, there was no statistically significant difference between the pre-plan and post-implantation needle number, implanted seed number, CI, HI, and EI ( P>0.05). In terms of postoperative dose quality assessment, eight cases were rated excellent (66.6%) and four cases were rated good (33.3%). Conclusions:Radioactive 125I seed implantation assisted by an optical navigation system and 3D-printing non-coplanar template can be accurately performed in the treatment of recurrent head and neck cancer, with good consistency between pre-plan and post-implant dosimetric parameters and thus of prospective potential in clinical application.

Objective:To compare preoperative planning parameters between non-coplanar and coplanar template-assisted radioactive seed implantation in the treatment of pancreatic cancers, in order to guide clinical application.Methods:Patients with pancreatic cancers who received external irradiation in the Peking University Third Hospital from Jan 2017 to May 2019 were selected.Their image information was imported into the brachytherapy planning system, and the non-coplanar plan and coplanar plan were designed individually.Each patient′s prescription dose was set to 110 Gy, and the activity of the radioactive seeds were 0.4 mCi(1 Ci=3.7×10 10Bq), respectively.For the two plans, the dose distribution was optimized and dosimetric parameters were compared, including the implantation needle number, the implanted seed number, the minimum prescription doses delivered to 90% and 100% of the target volume ( D90 and D100), mean percentages of volume receiving 100%, 150% and 200% of the prescription doses ( V100, V150 and V200), conformity index (CI), external index (EI), and homogeneity index (HI) of the target volume, as well as the doses of 2 cm 3 and 5 cm 3 ( D2 cm 3 and D5 cm 3) of the surrounding normal organs such as the small intestines, colon, duodenum, stomach, and spinal cord. Results:The implantation needle number in the coplanar plan was slightly higher than that in the non-coplanar plan, namely 18.63 vs. 16.45 ( t=-3.239, P <0.05). The implanted seed number was equivalent, namely 90.2 vs. 91.01, with no statistical difference ( P>0.05). There was no significant difference between D90, D100, V100, V150, V200, CI, EI, and HI in the target area of the two plans ( P>0.05). Meanwhile, there was no obvious difference in D2 cm 3 and D5 cm 3 of normal organs including the small intestines, colon, duodenum, stomach, and spinal cord ( P>0.05). Conclusions:With both the coplanar plan and the non-coplanar plan, the prescription doses can be achieved and meanwhile, there are very small differences in the doses of normal organs.Given that 3D-printing non-coplanar and coplanar templates have their own characteristics, it is necessary to choose them according to specific situations.

Objective To compare the preoperative and postoperative dosimetric results of radioactive seed implantation assisted by 3D printing template in the treatment of chest malignant tumor, and to examine the effect this technique on the precision of radioactive seed implantation.Methods A total of 21 patients who received 3D printing template-assisted CT-guided 125I seed implantation for chest tumors in 2016 were included in the study.The prescribed dose of the treatment was 110-180 Gy.Preoperative planning, individual template production, and puncture and seed implantation were performed in all patients, and the postoperative dosimetric results were then compared with the preoperative plan by assessing various dosimetric parameters including D90, MPD, V100, V150, CI, EI, and HI of gross tumor volume (GTV), D2cc of the spinal cord and aorta, and Dmean and V20 of the affected side of the lung.Statistical analysis was performed using the Wilcoxon non-parametric test.Results A total of 21 3D printing templates were designed and produced.The mean GTV volume (preoperative) of all patients was 77.1 cm3, and the mean number of implanted seeds was 68.In addition, the mean D90 of the postoperative GTV was 147.3 Gy.There were slight changes in the dosimetric parameters after treatment (P>0.05).Conclusions 3D printing template allows for accurate positioning and implantation of radioactive seeds during the treatment of chest tumor.Postoperative dosimetric parameters were consistent with those in the preoperative planning, indicating that the 3D printing template provides high precision for the treatment of chest tumor.

Objective To investigate the accuracy of 3D-printing non-coplanar template (3D-PNCT) assisted 125I seed implantation with CT guidance in the pelvic recurrent cervical between the preplan and post-plan dosimetric parameters.Methods Nine patients with pelvic recurrent cervical cancer received 125I seed implantation under CT guidance assisted with 3D-PNCT.A pre-plan based brachytherapy treatment planning system (B-TPS) assisted with 3D-PNCT for seed needle depth,direction and angle was designed.The dosimetry parameters including homogeneity index (HI),dose of 90％ target volume (Dg0),mPD,volume percent of 100％,150％ and 200％ prescribed dose V100,V150 and V200 and organ at risk between the pre-plan and post-plan were compared.Results Total seeds number was 675 (median 44,25-114) according to pre-plan,and 669 (median 47,25-113) seeds were implanted actually.138 needles need implant according to preplan,and 132 needles was implanted actually.The median angle deviation was 1.99 ° ± 2.94°(0 °-13 °).There was no significant difference of HI,EI and CI between perand post-plan.The differences of D90,MPD,V100,V150 and V200 between pre-and post-plan were not significant.Conclusions The confidence of pre-plan and post-plan for 3D-PNCT assisted 125I seed implantation in the pelvic recurrent cervical cancer could be accurately performed under CT guidance.

Objective To study the influence of fluoride on the expression of osteoprotegerin(OPG) mRNA and protein in suckling rat osteoblasts. Methods Osteoblasts obtained from calvarial of suckling Wistar rats were cultured in vitro in the media supplemented with NaF at a series of doses[O(control), 1,2 and 4 mg/L groups], and OPG mRNA expression and protein were evaluated by RT-PCR and ELISA methods, respectively. Results OPG mRNA expression in suckling rat osteoblasts cultured in vitro significantly increased after exposure to NaF for 48 h and 72 h(F=333.48,808.34,P<0.05). OPG mRNA expression in suckling rat osteoblasts cultured in vitro after exposure to NaF for 48 h at different doses(0.810±0.003, 0.819±0.031 and 0.870±0.044 for 1,2 and 4 mg/L groups, respectively) compared with that of control (0.800±0.040, all P<0.05). OPG mRNA expression further increased for 72 h exposure to NaF(0.933±0.047,1.031±0.051,1.240±0.062 for 1,2 and 4 mg/L, respectively), significantly higher than that of the control (0.805±0.020,all P<0.05) and corresponding groups at 48 h. NaF doses and time exposure exhibited a significant synergistic effect on OPG mRNA expression(F=2004.16, P<0.05). NaF also enhanced OPG protein expression in suckling rat osteoblasts cultured in vitro. Significant differences were observed only in 4 mg/L group(0.228±0.014,0.277±0.048) and control(0.205±0.012,0.229±0.010) at 48 h and 72 h (P<0.05). In addition, OPG protein expression at 72 h post-exposure was higher than that at 48 h,but there was no synergistic effect between concentration and time(F=1.21,P>0.05). Conclusions The results suggested that NaF could increase OPG mRNA and protein expression in suckling rat osteoblasts with a synergistic effect between the doses and exposure time.