This study aims to explore possible effect of RNA polymerase I subunit D (POLR1D) on proliferation and angiogenesis ability of colorectal cancer (CRC) cells and mechanism herein. The correlation of POLR1D and Yin Yang 1 (YY1) expressions with prognosis of CRC patients in TCGA database was analyzed. Quantitative realtime polymerase chain reaction (qRT-PCR) and Western blot were applied to detect expression levels of POLR1D and YY1 in CRC cell lines and CRC tissues. SW480 and HT-29 cells were transfected with si-POLR1D or pcDNA3.1-POLR1D to achieve POLR1D suppression or overexpression before cell migration, angiogenesis of human umbilical vein endothelial cells were assessed. Western blot was used to detect expressions of p38 MAPK signal pathway related proteins and interaction of YY1 with POLR1D was confirmed by dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). TCGA data showed that both POLR1D and YY1 expressions were up-regulated in CRC patients. High expression of POLR1D was associated with poor prognosis of CRC patients. The results showed that POLR1D and YY1 were highly expressed in CRC cell lines. Inhibition or overexpression of POLR1D can respectively suppress or enhance proliferation and angiogenesis of CRC cells. YY1 inhibition can suppress CRC progression and deactivate p38 MAPK signal pathway, which can be counteracted by POLR1D overexpression. JASPAR predicted YY1 can bind with POLR1D promoter, which was confirmed by dual luciferase reporter gene assay and ChIP. YY1 transcription can up-regulate POLR1D expression to activate p38 MAPK signal pathway, thus promoting proliferation and angiogenesis ability of CRC cells.

Objective To monitor the indoor radon concentration of urban residents in Shiyan, China, and to analyze the related influencing factors. Methods From April to July, 2019, RSKS standard detectors were used to measure the indoor radon concentration of 125 households in Shiyan, and the results were analyzed. Results The indoor radon concentration of residents in Shiyan showed a skewed distribution, ranging from 13.8 to 145 Bq/m³, and M (P₂₅,P₇₅) was 38.3 (29.0,62.0) Bq/m³. The estimated annual effective dose of radon and radon daughters from inhalation was 0.52-5.50 mSv, and M (P₂₅,P₇₅) was 1.45 (1.10, 2.36) mSv, which was consistent with literature. Building structure (H = 14.10, P < 0.001), floor (H = 24.41, P < 0.001), and geographical region (H = 8.963, P < 0.05) were influencing factors of indoor radon concentration, and the differences were significant. Conclusion The indoor radon concentration of urban residents in Shiyan is lower than the national standard limit. However, in daily life, it is still necessary to take appropriate measures to reduce the concentration of indoor radon as much as possible.

Objective To determine the current status of occupational internal exposure to ¹³¹I in the thyroid of nuclear medicine workers, to explore the influencing factors for internal exposure, and to provide a basis for the radiation safety management of nuclear medicine. Methods The cluster sampling method was used to select 162 workers practicing ¹³¹I treatment in 24 hospitals in Hubei Province, China. Thyroid ¹³¹I activity levels were measured in vitro using a portable γ-spectrometer, and the committed effective dose was estimated. Results The thyroid ¹³¹I activity detected in 13 (54.17%) hospitals was above the lower limit of detection of the instrument. Two hospitals had the highest detection rates, 62.50% and 61.90%; the difference was significant compared with the remaining 11 hospitals (P < 0.0001). Thyroid ¹³¹I was detected in 34 workers in total, with a detection rate of 20.99% and a mean activity of 179.09 ± 138.71 (6.02-589.74) Bq. The highest detection rates were found in cleaners and nurses, which were 35.71% and 33.33%, respectively, with no significant difference in detection rate between positions (least P > 0.08). The mean value of the committed effective dose was 0.68 ± 0.52 (0.02-2.22) mSv/a in the 34 workers. Conclusion The ¹³¹I consumption and workplace ventilation may be important factors affecting the level of internal exposure. It is important to strengthen the training of nuclear medicine workers on radioprotection and workflow management, as well as the regular monitoring of occupational internal exposure for ¹³¹I treatment-related workers.

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.
Humans ; Male ; Antiviral Agents/therapeutic use* ; China ; Hepatitis C/drug therapy* ; Hepacivirus ; Logistic Models

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3

Objective:To provide a retrospective analysis of the levels of occupational external exposure of radiation workers in Hubei province from 2009 to 2018 in a way to prevent and control its risks.Methods:The external individual doses were surveyed for 50 070 radiation workers between 2009 and 2018 by the effort of the Hubei Provincial Center for Disease Control and Prevention. Under the relevant national standards, the external radiation doses to radiation workers were conducted by using TLDs.Results:The average annual collective effective dose to radiation workers in a 10 years period was 1.93 man·Sv, the median of average annual effective dose of 0.14 mSv ( P25- P75: 0.06-0.30 mSv), and the average annual effective dose of 0.40 mSv. The annual effective doses received by 46 562 workers were less than 1 mSv, accounting for 92.99% of the total monitored workers. The annual effective dose varied dependent on occupational categories, showing a year-by-year decline trend and staying at a low level after 2012. The relative high radiation doses were seen in nuclear medicine and interventional radiology in medical applications, non-destructive testing and well logging in industrial applications, and other types of radiation applications. Conclusions:The average annual effective dose decreased year in a by year manner and kept at a low level. This indicated that the radiological protection measures taken during the 10 years ensure the health of workers. The continuous monitoring result suggest that much more attention should be paid to such categories workers as nuclear medicine, interventional radiology, non-destructive testing, well logging and others through improving radiation protection measures.

Objective To assess the medical radiation exposure frequency and find out the main factors related to the collective dose derived from X-ray diagnosis procedures. Methods A survey of 3 178 hospitals was conducted to collect the basic information such as types of medical radiation, allocation of radiological diagnosis and treatment devices, the frequency of radiologic examinations, etc. By using a stratified sampling method，36 hospital were selected and more specific details, including 26 types of diagnostic radiologic examinations, were collected to estimate the collective dose to the population in Hubei, combining with the previous literature. Results A total number of 6 843 radiological diagnosis and treatment devices were covered and 33 771 855 medical radiologic procedures were counted in this survey. The result showed a annual frequency of 569.79 examinations per 1 000 population for all types of procedures. A large variation was revealed among different areas and the highest area was with a 4-fold frequency of the lowest area. Although tertiary hospitals accounted for 4.40% of the total hospitals, 48.42% procedures were carried out in them. The collective effective dose from X-ray diagnosis in Hubei was 65 399.55man·Sv, and the average annual effective dose was 1.10mSv, while contribution from CT scans accounted for 86.90% of the dose. Conclusion The frequency of medical radiologic procedures presented a consistent increase in Hubei province, with a uneven development among hospitals from urban and rural areas, or from different regions, or from different levels. Among all types of X-ray examinations, CT scan frequency had the fastest growth rate and accounted for the major annual collective effective dose. In order to reduce the health risk from medical radiologic exposure, CT scan need to be applied more properly and the radiation dose per single CT scan need to be limited to a reasonable level.

Objective: To study a method to measure the doses to planned target volume (PTV) and organ at risk (OAR) and 2D dose distribution in IMRT by using TLD and radiochromic film for a verification purpose. Methods: Totally 7 different types of medical linear accelerators were selected from seven hospitals in Hubei province. A polystyrene phantom provided by IAEA was CT scanned and then the scanned images were returned to the Treatment Planning System (TPS) for determining the prescribed doses to PTS and OAR and the corresponding MU. After the phantom was irradiated with 6 MV X-ray, the TLDs and films were transmitted to the secondary standard dosimetry laboratory of China CDC for measurement and estimation. Results: The IAEA required the relative deviations between TLD-measured and TPS-planned doses to OAR and PTV be within ±7.0%. For PTV, the measured-to-planned deviation values for 7 accelerator were within -5.4% to 6.5%, all consistent with the IAEA requirements. For OAR, the values for 5 accelerators were within -2.2% to 6.7%, not consistent the requirements, whereas the values for the other 2 were -8.6% and 8.2% respectively, beyond the required values. The IAEA required that the 2D dose distribution 3 mm/3% pass rate be higher than 90%. The measured values for 7 accelerators were in the range of 90.3%-98.9%, all consistent with the requirements. Conclusions It is feasible scientifically and easy to operate in practice for using TLD and film to carry out dose verification in IMRT. It would be advisable to apply this method to quality verification in IMRT in medical institutions to the extent possible.

Objective To verify the leaf positioning accuracy of multi-leaf collimator (MLC) in intensity modulated radiation therapy (IMRT) by using radiochromic films to provide references for IMRT quality control.Methods Medical linear accelerators of different designs,owned by 7 first-class hospitals at grade-3 in Hubei,were selected for this verification study.Five strip picket fence pattern was created by treatment planning system (TPS).Each strip was 0.6 cm wide with a 3 cm strip separation.MLC leaf positions,positioning bias and opening widths were then measured with EBT2 radiochromic films.Results According to IAEA standards,the film-measured and TPS planned MLC leaf position difference was ±0.5 mm.The difference of MCL strip position of No.5 and No.7 accelerator was 0.7 and-1.0 mm,respectively,not in line with the IAEA standards.The difference of film-measured MLC leaf position between each pairs and all pairs of leaves of 7 accelerators were all within ± 0.5 mm,in line with the IAEA requirements.As required by IAEA,the difference of opening width of MLC leave of each pair relative to the averaged widths of all pairs should be within ±0.75 mm.The filem-measured values from 7 accelerators ranged from-0.6 to 0.5 mm,all in line with the IAEA standards.Standard deviation of opening width of all leaves were required to be within 0.3 mm.The measured values from 7 accelerators ranged from 0.1 to 0.2 mm,in line with the IAEA standard.Conclusions The use of EBT2 radiochromic films to verify MLC leaf positioning accuracy is an important means of quality control owing to its simplicity and high measurement accuracy.It is recommended for verification use at a large scale.