A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis / 中华医学杂志(英文版)

BACKGROUND@#Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.@*METHODS@#We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.@*RESULTS@#The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1 ) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1 . The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes.@*CONCLUSION@#The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1 .@*TRIAL REGISTRATION@#No. NCT00454519 ( https://clinicaltrials.gov/ ).

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis / 中华医学杂志(英文版)

BACKGROUND@#Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1 ), the most frequently altered proto-oncogene in hepatic neoplasms.@*METHODS@#Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-catenin Δ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-catenin Δ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro . Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV ); β-catenin lox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer.@*RESULTS@#MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV ; β-catenin lox(ex3)/+ mice, which stimulated concurrent Ctnnb1- activated mutation and HBV infection in liver cancer.@*CONCLUSION@#MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Measurement and analysis of dose exposure in childhood intussusception reduction / 中国辐射卫生

Objective To investigate the dose of radiation in children under going X-ray-guided air enema reduction, and to provide a basis for reducing the risk of radiation injury in pediatric patients. Methods Data were collected from children with intussusception who were treated with air enema. The experimental conditions of high, medium, and low doses of three age groups were analyzed. Phantoms were used to simulate the operation, and the radiation dose was measured using a thermoluminescence system. Results In children with intussusception, the success rate of air enema under the guidance of X-ray was 88% (including secondary intussusception), with anearly re-intussusception rate of 8%. The effective dose of treatment ranged from 0.57 to 12.33 mSv, and the tissues and organs with high absorbed dose were mainly in the chest and abdomen. Conclusion Children in different groups are exposed to significantly differentand relatively high doses. The operators are recommended to use ultrasonic guidance. With X-ray guidance, the exposure time should be minimized and protective equipment for children should be used.

Impact of COVID-19 on chest CT scan frequency in a general hospital / 中国辐射卫生

@#<b>Objective</b> To explore the effect of coronavirus disease 2019 (COVID-19) on the frequency of chest CT scan. <b>Methods</b> A retrospective study was conducted to extract information on the number of outpatient, emergency, and inpatient visits and patients who had chest CT imaging examination from January 1 to December 31, 2020 and in the same period in 2019 through the hospital’s medical data platform for analysis, and the chi-square test was used to analyze whether the difference in the proportion of patients who had chest CT imaging examination between 2019 and 2020 was statistically significant. <b>Results</b> The proportion of outpatients and emergency patients with chest CT examination was significantly higher in 2020 than in 2019 (2.48% <i>vs</i> 1.47%, <i>χ</i>² = 581.7, <i>P</i> < 0.000). The proportion of inpatients who underwent chest CT examination was significantly higher in 2020 than in 2019 (35.47% <i>vs</i> 28.01%, <i>χ</i>² = 182.0, <i>P</i> < 0.000). <b>Conclusion</b> Under the COVID-19 epidemic, the proportion of chest CT examination in this hospital in 2020 shows a significant upward trend compared with the same period in 2019, which will increase the collective dose due to medical exposure, and the hospital should pay attention to the determination of the legitimacy of chest CT scan.

Measurement and analysis of induced radioactivity in medical electronic linear accelerator / 中国辐射卫生

Objective By measuring the induced radioactivity of the medical electron linear accelerator, and analyzing the measuring results and the measuring process, the cooling law of the induced radioactivity was studied, to provide basic data for evaluating additional doses to patients, medical staff and the public. Methods Five Medical Electron Linear accelerators were used to measure the induced radioactivity by using automes-6150AD6/H+6150AD-b/H x-γ radiation peripheral dose equivalent rate meter for environmental monitoring. Results The level of induced radioactivity of 5 medical electron linear accelerators is related to the factors such as measuring position and time: 10 second after the end of beam output, the maximum dose equivalent rate is 5.55 μSv/h around 5 cm on the surface of the head housing of the accelerator, and the maximum ambient dose equivalent rate at 1 m from the fixed point of the housing is 4.07 μSv/h, 5 minutes after the end of output, the maximum dose equivalent rate is 2.11 μSv/h around the 5 cm surface and 1.77 μSv/h around the 1 m fixed point. Conclusion The measured radioactivity induced by the medical electron linear accelerator gradually cools over time, the measurement valuesare maintained in a relatively fixed range, and the fluctuation range of the values is narrow.

Monitoring results and analysis of 131I in the air of workplace treated with iodine / 中华放射医学与防护杂志

Objective:To understand the activity concentration of 131I aerosol in the air of the iodine treatment workplace and estimate the internal dose of 131I inhaled by medical staff in nuclear medicine. Methods:Using CF-1001BRL portable large capacity air sampler, the 131I aerosol in the iodine treatment workplace of nuclear medicine department of 6 hospitals in Shandong province was collected by iodine box, and the HPGe-γ energy spectrometer was used to measure the samples. The 131I activity concentration in iodine treatment workplace at 6 hospitals was obtained, and the internal dose to medical staff was estimated. Results:The 131I activity concentration in the air in iodine treatment workplaces at 6 hospitals ranged from 3.64 to 2.94×10 3 Bq/m 3. The 131I activity concentration in the controlled area (ward, patient passageway, subpacking room, operation administration room) was significantly higher than that in the supervised area. The highest 131I activity concentration, 2.62×10 2 Bq/m 3, in the supervised area was found in the medical care passageway. The estimated effective dose to nuclear medicine workers was 0.07-5.68 mSv, not exceeding the national limit. Conclusions:The phenomenon of 131I aerosol contamination still exists in the iodine treatment workplaces of nuclear medicine departments in hospitals, so it is necessary to carry out internal radiation monitoring for nuclear medicine departments all around the country, and explore more reasonable protection standards and methods.

Simulated experimental measurement of exposure dose to patients from endoscopic retrograde cholangiopancreatography operation / 中华放射医学与防护杂志

Objective@#To estimate the doses to patients from ERCP operation through experimental measurements.@*Methods@#A retrospective analysis was made of 56 ERCP operations in three hospitals, and meanwhile, the tube voltage and current, fluoroscopy time, accumulated doses, DAPs (dose-area product) and photographic frames were also recorded for statistical analysis. Three cases of RECP operation that had led to high, medium and low DAP values were selected, respectively, as high, medium and low dose groups based on anthropomorphic phatom (AP). ERCP operation was simulated on AP on the basis of putting TLDs in it. The absorbed doses of organs were measured while effective doses while calculated.@*Results@#The effective doses for high, medium and low groups were 2.69, 11.52 and 39.27 mSv, respectively. The effective dose was 14 times higher in high dose group than that in low group. The highest organ doses for three groups were all concentrated in the irradiation fields.@*Conclusions@#Organ doses from ERCP phantom experiments vary largely in different groups. Compared with phantom experiments of other interventional types, ERCP can be regarded as one of interventional means leading to high-dose. It is advisable to reasonably and safely use intervention diagnosis and therapy and in order optimize radiation doses to patients.

Simulated experimental measurement of exposure dose to patients from endoscopic retrograde cholangiopancreatography operation / 中华放射医学与防护杂志

Objective To estimate the doses to patients from ERCP operation through experimental measurements.Methods A retrospective analysis was made of 56 ERCP operations in three hospitals,and meanwhile,the tube voltage and current,fluoroscopy time,accumulated doses,DAPs (dose-area product) and photographic frames were also recorded for statistical analysis.Three cases of RECP operation that had led to high,medium and low DAP values were selected,respectively,as high,medium and low dose groups based on anthropomorphic phatom (AP).ERCP operation was simulated on AP on the basis of putting TLDs in it.The absorbed doses of organs were measured while effective doses while calculated.Results The effective doses for high,medium and low groups were 2.69,11.52 and 39.27 mSv,respectively.The effective dose was 14 times higher in high dose group than that in low group.The highest organ doses for three groups were all concentrated in the irradiation fields.Conclusions Organ doses from ERCP phantom experiments vary largely in different groups.Compared with phantom experiments of other interventional types,ERCP can be regarded as one of interventional means leading to high-dose.It is advisable to reasonably and safely use intervention diagnosis and therapy and in order optimize radiation doses to patients.

Survey on frequency of medical X-ray diagnosis in Shandong province / 中华放射医学与防护杂志

Objective To analyze the distribution characteristics and influencing factors of X-ray diagnostic imaging in Shandong province,and to estimate the application frequency of X-ray diagnostic imaging in the province,and provide data support for X-ray equipment.Methods A random sampliug method was used to extract 32 medical institutions as respondents from 10 prefecture-level cities in Shandong province.The basic information of medical institutions and the age,sex,examination and procedure of the subjects were analyzed.The distribution of the X-ray application was analyzed and estimated by using a multiple linear regression model.Results Totally 14 694 085 subjects were surveyed,and the proportion of male and female in the sample was not completely uniform.A total of 2 099 155 X-ray diagnostic information was collected in 2016,and the frequency of conventional radiography was the highest,accounting for 59.49％.The next was CT examination,accounting for 28.34％.The frequency of the two examinations showed an increasing trend with the age of subjects.For the total frequency of conventional diagnostic radiography and CT examination,the tertiary hospitals accounted for the highest proportion of the total,up to 52.13％,while the secondary hospitals accounted for the relatively low proportion of 30.09％,and the primary hospitals the lowest with 17.77％.The chest radiography had the highest proportion in conventional radiography accounting for 32.79％ of the total frequency of X-ray diagnostic imaging,and the head procedure had the highest proportion in CT examination,accounting for 10.07％ of the total frequency of X-ray diagnostic imaging.The fluoroscopy,mammography and dental radiography were mainly concentrated in the tertiary hospitals,and the primary hospitals had mainly radiography.Multiple linear regression models showed that the frequency of application of conventional X-ray diagnostic imaging (including radiography,fluoroscopy,dental radiography and mammography) was positively correlated with equipment quantity,number of outpatient and emergency patients,and tertiary hospitals (t=4.334,3.615,2.339,P＜ 0.05).CT examination was positively correlated with equipment quantity and the number of inpatient (t =2.167,2.595,P＜0.05).The frequency of conventional X-ray diagnostic imaging and CT examination in Shandong province were estimated about 491.17 examinations per 1 000 population and 258.17 examinations per 1 000 population respectively.Conclusions The frequency of X-ray exposure in Shandong province increased significantly compared with that during the " 9th Five-Year Plan" period.All relevant departments should take effective measures to strengthen medical radiation protection and reduce radiation risk.

Establishment of a model of hydrogen peroxide-induced injury in pulmonary artery endothelium cells and relevant mechanisms of oxidative stress / 中华心血管病杂志

Objective@#To establish a hydrogen peroxide (H2O2) induced injury model of pulmonary artery endothelial cells (PAECs) and explore the molecular mechanisms of oxidative stress on the structure and function of PAECs in this model.@*Methods@#Human PAECs were treated with H2O2 at different concentrations (25, 50, 100, 200, 400, 800, 1 600, 3 200, 6 400 μmol/L) for 4 and 24 h, respectively. The PAECs survival curve was obtained according to the cell viability measured by CCK-8 assay. The cell apoptosis of PAECs was detected by flow cytometry. The reactive oxygen species (ROS) generation and mitochondrial activity were measured using small molecule fluorescent probes. Proteins were extracted and the phosphorylation levels of signal molecules in PAECs were detected by Western blot assays.@*Results@#(1) The effect of H2O2 at various concentrations on cell viability of PAECs: cell viability of PAECs decreased in proportion to increasing concentration of H2O2 after incubation for 4 h. The half maximal inhibitory concentration (IC50) of PAECs exposed to H2O2 for 4 and 24 h were 397.00 and 488.77 μmol/L, respectively. (2) The effect of H2O2 on cell apoptosis of PAECs: After H2O2 incubation for 4 h, proportions of PAECs at late-apoptosis ((22.58±3.69) %) and necrotic stage( (11.86±4.27)%) were significantly higher than those of control PAECs at late-apoptosis stage( (3.41±1.44)%, P<0.01) and at necrotic stage ((1.94±1.15) % , P<0.05). The survival rate of PAECs post H2O2 was dramatically lower than that of control PAECs ((7.98±3.21)% vs. (48.89±8.08)%, P<0.01). However, there is no statistical difference between both groups regarding to the early apoptosis. (3) The effect of H2O2 on mitochondrial activity and ROS production of PAECs: the mitochondrial activity and ROS generation of PAECs treated by H2O2 were significantly increased compared to those in control PAECs (P<0.01). (4) The effect of H2O2 on signaling molecules in PAECs: there was a significant increase in phosphorylation level of Akt in PAECs incubated with H2O2 for 30 minutes compared to that in control PAECs (P<0.01), while there was no significant difference in levels of Akt between H2O2 treated PAECs and control PAECs. Phosphorylation level of JNK as well as p38 were also significantly upregulated in H2O2 treated PAECs (P<0.01).@*Conclusion@#H2O2 at the concentration of 400 μmol/L could induce human PAECs injuries via the regulation of Akt and MAPK signaling pathways.

Imaging findings of primary bone malignant fibrous histiocytoma in long bone / 中国医师进修杂志

Objective To investigate the imaging findings of primary bone malignant fibrous histiocytoma (PBMFH) in long bone. Methods MRI and XV ray examinations were performed in 10 patients with PBMFH in long bone confirmed by histology. CT scans were performed in 6 cases. Results Nine cases had single and 1 case had multiple lesions of single bone. Seven cases showed osteolytic bone destruction, and 3 cases showed mixed bone destruction. Only 1 case showed periosteal reaction. Gross bony ridge was seen in 3 cases on CT scan. All the patients demonstrated isointensity or hypointensity on T1WI, and slight hyperintensity signal on T2WI. Necrosis was seen in the lesion of 10 cases. Four cases showed obvious but heterogeneous enhancement after contrast medium injection. Eight cases had soft tissue mass beyond the scope of bone destruction. Conclusions Some imaging features may suggest the diagnosis of PBMFH in long bone.

Clinical research of single glucocorticoid treatment and glucocorticoid joint cyclophosphamide treatment on thyroid-associated ophthalmopathy / 中国基层医药

ObjectiveTo explore the effect of single glucocorticoid treatment and glucocorticoid joint cyclophosphamide treatment on thyroid-associated ophthalmopathy.MethodsRetrospective analysis of clinical data of 35patients used single glucocorticoid( single medicine group) and 16 patients used glucocorticoids joint cyclophosphamide(joint group) was carried out.ResultsThe effective rate of joint group(93.8％ ) was significantly higher than single drug group (68.6％) ( x2 =3.87,P ＜ 0.05).Simple using glucocorticoid had significant treatment effect at CAS score,prominent eyes degrees,soft tissue inflammation score,but the curative effect was significantly lower than the joint group ( P ＜ 0.05 ).The adverse reaction rate had no significant difference between two groups.ConclusionCompared to single glucocorticoid treatment,the glucocorticoid joint cyclophosphamide treatment had better effect and lower adverse reaction rate,especially suitable for patients who had no effect or low effect on hormone therapy.

The study of relationship between insulin resistance and dyslipidemia in type 2 diabetes associated with nonalcoholic fatty liver / 中国基层医药

Objective To study the relationship between insulin resistance(IR) and dyslipidemia and nonalcoholic fatty liver disease(NAFLD) in type 2 diabetes mellitus(T2DM).Methods Seventy-two patients were divided into fatty liver group and non-fatty liver group.Blood lipid,blood glucose(BG),blood pressure,fasting and 2-hour serum insulin were measured.At the same time,HOMA-IR,body weight index(BMI),the waist hip ratio(WHR) were calculated.the diagnosis of the fatty liver was learned from the check according to an image.Results Compared with the non-fatty liver group,the average levels of TG,LDL-C,FIns,2hIns,HOMA-IR,BMI,WHR,alanine aminotransferase(ALT),?-glutamyl transpeptidase(?-GT),uric acid and diastolic pressure were significantly higher in fatty liver group(P0.05).Conclusion Compared with the non-fatty liver patients,T2DM patients complicated with NAFLD have more serious IR,dyslipidemia and obesity.It indicates that IR has a significant influence on the outbreak of the fatty liver;The NAFLD is probably one of components of metabolic syndrome.