Objective To implement the finite discontinuity?volumetric modulated arc therapy ( FD?VMAT) in the Pinnacle planning system, and to investigate its clinical significance. Methods Eight patients with thoracic esophageal cancer in our hospital were enrolled as subjects. FD?VMAT was fulfilled in the Pinnacle planning system using a developed program. FD?VMAT, VMAT, and fixed?field intensity?modulated radiotherapy ( IMRT ) plans were designed for each patient. The conformity index ( CI ) and homogeneity index ( HI) of the planning target volume ( PTV) ,doses to organs at risk,passing rate for plan verification,number of monitor units,and treatment time were used to evaluate the plans. Comparison between different plans was made by paired t test. Results For the PTV,there was no significant difference in CI between FD?VMAT and VAMT ( P=0?186 );FD?VMAT had a significantly worse HI than VMAT ( P=0?001);however,both the CI and HI were significantly improved in FD?VMAT than in IMRT ( P=0?006, 0?002) . Compared with IMRT, FD?VMAT, retaining the advantage of VMAT, had pulmonary V20 and V30 significantly reduced by 19?79% and 20?32%,respectively (P=0?000,0?000).For the pulmonary low?dose regions (≤V5 ) ,FD?VMAT retained the advantage of IMRT and had lower doses than VMAT. Particularly, pulmonary V2 was significantly reduced by 16?79%(P=0?000).The mean lung dose was significantly lower in FD?VMAT than in VMAT or IMRT (P=0?001,0?000).There were no significant differences in D1cc to spinal cord PRV,heart V30,or passing rate for plan verification between the three therapies. The heart V40 and mean heart dose in FD?VMAT were similar to those in VMAT (P=0?175,0?468),but significantly lower than those in IMRT ( P=0?021,0?002) . FD?VMAT had a larger number of monitor units and longer treatment time than VMAT. Compared with IMRT, the number of monitor units and treatment time were reduced by 13?6% and 49?6% in FD?VMAT,respectively. Conclusions Compared with VMAT and IMRT, the application of the developed FD?VMAT in the treatment of thoracic esophageal cancer can further reduce the lung dose while keeping the PTV coverage,protection of the heart and spinal cord,and high efficacy. FD?VMAT is a new therapy available for thoracic esophageal cancer.

Objective:To evaluate the effects of a booster immunization with a candidate tetanus toxoid, reduced diphtheria toxoid and acellular pertussis combined vaccine (Tdap) in a rat model after primary vaccination with diphtheria, tetanus, acellular pertussis and Sabin strain inactivated poliovirus combined vaccine (DTacP-sIPV) or diphtheria, tetanus, acellular pertussis, inactivated poliovirus and haemophilus type b combined vaccine (DTacP-IPV/Hib) for further preclinical study.Methods:Wistar rats were randomly divided into three groups and respectively immunized with a self-developed DTacP-sIPV, a marketed DTacP-IPV/Hib and normal saline at 0, 1, and 2 months of age. Serum levels of antibody against each component in each group were detected before immunization and after each dose. A booster dose of the candidate Tdap was given 10 months after primary immunization. Serum levels of antibody against each component in each group were detected before, 1 month and 6 months after the booster immunization.Results:One month after three doses of primary immunization, the geometric mean titers (GMT, Log2) of antibodies against diphtheria toxoid (DT), tetanus toxoid (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) in the DTacP-sIPV group were 17.41, 18.34, 18.11, 19.93 and 13.91, respectively, and the seroconversion rates of these components all reached 100%. Ten months after primary immunization, the GMTs of antibodies against DT, TT, PT, FHA and PRN decreased to 15.17, 14.26, 13.60, 14.51 and 10.39, respectively, and the seroconversion rates remained above 89%. One month after booster immunization, the GMTs of antibodies against DT, TT, PT and FHA in the DTacP-sIPV and DTacP-IPV/Hib groups were 16.49/17.26, 16.80/17.63, 16.70/17.74 and 18.48/19.26, respectively, and the seroconversion rates of these components all reached 100% with no significant difference between the two groups ( P>0.05). The GMTs of anti-PRN antibody in the DTacP-sIPV and DTacP-IPV/Hib groups were 13.07 and 11.00, and the seroconversion rates were 100% and 88%, which were higher in the DTacP-sIPV group than in the DTacP-IPV/Hib group ( P<0.05). Six months after booster immunization, the GMTs of antibodies against DT, TT, PT, FHA and PRN in the DTacP-sIPV and DTacP-IPV/Hib groups decreased to 15.74/14.87, 15.07/15.14, 14.84/15.73, 16.62/16.37 and 11.44/9.96, respectively, and the seroconversion rates remained above 88%. Conclusions:Booster vaccination with the candidate Tdap vaccine induces humoral immune response following primary immunization with DTacP-sIPV or DTacP-IPV/Hib in the Wistar rat model, while the antibody titer decreases with time.

Objective:To assess the shielding requirements of low energy X-ray intraoperative radiotherapy room under the domestic and foreign standards and guidelines, to measure the sured transmission factors for a range of shielding materials, the ambient dose equivalent rate around concerned positions and the shielding effect of protective devices, so as to provide references for shielding design of such radiotherapy units and applications of radiological protection devices.Methods:The required shielding thicknesses for a treatment room with INTRABEAM intraoperative radiotherapy system were calculated under the Chinese national standard GBZ 121, IPEM report No. 75 and NCRP report No. 151, respectively. The transmission factors for a range of shielding materials including solid water slab, shielding sheet and shielding apron were measured. Moreover, the ambient dose equivalent rates were measured under the simulated working conditions and the shielding effectiveness of a lead screen was evaluated.Results:The required lead thicknesses calculated under different standards and guidelines were less than 0.6 mm for all the concerned points, with the differences at sub-millimeter level. The low energy X-rays generated by this equipment attenuated rapidly in the shielding materials. The measured transmission factors of 0.05 mm lead equivalent shielding sheet and 0.25 mm lead equivalent shielding apron were 0.068 and 0.003 8, respectively. When the radiation was delivered using spherical applicator without any attenuation, the ambient dose equivalent rates at 1 m and 2 m from the X-ray source were 10.7 and 2.6 mSv/h, respectively. The corresponding measurement values decreased to 3.8 and 0.9 μSv/h, respectively, when the spherical applicator was inserted into a small water tank. Meanwhile, the ambient dose equivalent rate at 2 m was reduced to the background level when using protective screen.Conclusions:The shielding requirements for a low energy X-ray intraoperative radiotherapy facility are minimal, with low effective energy of X-rays generated by this equipment, but the dose rate close to the unshielded radiation source is high. The shielding scheme of treatment room should be optimized in design and the protective device should be used in a reasonable way.

Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Here we investigated that signal transducer and activator of transcription 3 (STAT3)-mechanistic target of rapamycin (mTOR) signaling mediates the suppression of ghrelin induced by IL-27. Co-localization of interleukin 27 receptor subunit alpha (WSX-1) and ghrelin was observed in mouse and human gastric mucosa. Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57BL/6J mice and high-fat diet-induced-obese mice. IL-27 inhibited the production of ghrelin in mHypoE-N42 cells. Inhibition of mTOR activity induced by siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells. siRNA also abolished the inhibitory effect of IL-27 on ghrelin. IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells. In conclusion, IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.

Arrhythmogenic cardiomyopathy (ACM), a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes, accounts for 20% of sudden cardiac death and lacks effective treatment. It is often caused by mutations in desmosome proteins, with Desmoglein-2 (DSG2) mutations as a common etiology. However, the mechanism underlying the accumulation of fibrofatty in ACM remains unknown, which impedes the development of curative treatment. Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2 (CS-Dsg2 ^-/-). Heart failure and cardiac lipid accumulation were observed in CS-Dsg2 ^-/- mice. We demonstrated that these phenotypes were caused by decline of fatty acid (FA) β-oxidation resulted from impaired mammalian target of rapamycin (mTOR) signaling. Rapamycin worsened while overexpression of mTOR and 4EBP1 rescued the FA β-oxidation pathway in CS-Dsg2 ^-/- mice. Reactivation of PPARα by fenofibrate or AAV9-Pparα significantly alleviated the lipid accumulation and restored cardiac function. Our results suggest that impaired mTOR-4EBP1-PPARα-dependent FA β-oxidation contributes to myocardial lipid accumulation in ACM and PPARα may be a potential target for curative treatment of ACM.