Objective:To investigate the effects and mechanisms of copper transporter 1 (CTR1) in radiation induced intestinal injury in vitro. Methods:Human small intestinal epithelial cells (HIEC) were irradiated with 2, 4, 6, 8 Gy of X-rays and rat intestinal epithelial cells (IEC-6) were irradiated with 5, 10, 15, 20 Gy of X-rays. At 2, 4, 8, 24, and 48 h after irradiation, the expression of CTR1 was detected by Western blot assay. In some experiments, HIEC and IEC-6 cells were transfected with CTR1 shRNA and then exposed to X-rays. Copper levels were detected by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The radiosensitivity of cells was verified by colonogenic assay, the cellular reactive oxygen species (ROS) level and DNA damage were detected to further explore the related mechanism. In addition, Western blot was applied to detect the expressions of antioxidants and cuproptosis associated proteins in enterocytes after silencing CTR1 or irradiation.Results:The expression of CTR1 was increased by X-ray irradiation in a dose-dependent manner ( t=3.53, 3.45, 6.37, 11.11, 11.13, P<0.05). CTR1 expression was successfully diminished by CTR1 shRNA adenovirus vectors. According to the survival curves, the enhancement ratios of the radiosensitivity of HIEC and IEC-6 cells with CTR1 knocking-down were 1.146 and 1.201, respectively. Radiation-induced copper accumulation was alleviated after CTR1 silencing in IEC-6 cells ( t=3.10, P<0.05). At 0.5 h after irradiation, the ROS production in the CTR1 knockdown group was significantly lower than that in the control group ( t=5.23, 2.96, P<0.05). At 1 h after irradiation, the protein expression of γ-H2AX in the CTR1 knockdown group was obviously lower than that in the control group ( t=7.50, 4.29, P<0.05). The expressions of Nrf2 and HO-1 were increased after irradiation, which could be further increased after CTR1 silencing. In addition, cuproptosis associated protein DLAT, LIAS and FDX1 were reduced post-irradiation, which were recovered after CTR1 silencing. Conclusions:The radioresistance of HIEC and IEC-6 cells was enhanced after CTR1 silencing, possibly through the intracellular ROS and cuproptosis pathway.

Objective To investigate the accuracy of sequential organ failure assessment (SOFA) scoring in emergency physicians in Beijing. Methods Emergency physicians from 8 hospitals in Beijing in January 2018 were demanded to complete a SOFA questionnaire which was developed on ''wenjuanxing'' website and submit via cell phone. All participants were divided into urban center group (UC group) and no-urban center group (NUC group) based on the hospital's location. The accuracy rate of components and total score of SOFA along with the mistakes were evaluated, and the results of the two groups were compared. Results ① The questionnaire was sent to 217 emergency physicians of the 8 hospitals, and 197 qualified questionnaires were received with 109 of NUC group and 88 of UC group, respectively, the total response rate was 90.8%. Compared with those from NUC group, UC physicians had older ages [years:37 (32, 42) vs. 34 (29, 40), Z = -2.554, P = 0.011] and higher education level [postgraduate degree 76.1% (67/88) vs. 40.4% (44/109), χ2= 25.327, P < 0.001], and more of them experienced SOFA scoring [62.5% (55/88) vs. 45.9% (50/109), χ2= 5.409, P = 0.020]. Other baseline characteristics such as gender, working years, professional title and training experience were not different between the two groups. ② The accuracy rate of total SOFA score was 62.4% (123/197) in the whole cohort, and UC group was lower than that of NUC group, but the difference was not significant [56.8% (50/88) vs. 67.0% (73/109), χ2= 2.141, P = 0.143]. While comparing the accuracy of individual variable/system of SOFA, the accuracy rate of norepinephrine of UC group was much higher than NUC group [80.7% (71/88) vs. 66.1% (72/109), χ2= 5.235, P = 0.022], but the accuracy of Glasgow coma scale (GCS) was much lower in NUC group [38.6% (27/70) vs. 81.6% (71/87), χ2= 30.629, P < 0.001]. Other variables of SOFA were not different between the two groups. ③Based upon the results of all submitted questionnaires, 566 mistakes were identified. It was indicated that the mistakes per capital was 2.9 in the whole cohort and in the two groups. The first type mistakes which caused by carelessness (including calculating error, filling error, choosing error) were 233 times. The calculating error in norepinephrine from NUC physicians was higher than the UC group [33.9% (37/109) vs. 19.3% (17/88), χ2= 5.235, P =0.022], there was no significant difference in any other first type mistakes between the two groups. The total second type mistakes caused by misunderstanding of SOFA (including using wrong variables, not using the worst value within 24 hours, and incorrect GCS score) were 333 times in the whole cohort. GCS error [61.8% (42/88) vs. 16.9% (14/109), χ2=32.292, P<0.001], and using urine output per hour instead of urine output per 24 hours [15.9% (14/88) vs. 4.6% (5/109), χ2= 7.162, P = 0.007] were much higher in UC group than NUC group. Conclusions The total accuracy of SOFA scoring in the investigated emergency physicians of 8 hospitals in Beijing was not good. Mistakes causing by carelessness or misunderstanding of score rules were similar. It is necessary to apply strict training in SOFA scoring.

OBJECTIVETo study the relationship between non-alcoholic steatohepatitis (NASH) and atherosclerosis in young and middle-aged patients, and to provide clinical evidence that will aid in prevention and prediction of development of atherosclerosis or cardiovascular diseases in patients with non-alcoholic fatty liver disease (NAFLD).

METHODSFifty-one patients with biopsy-proven NAFLD (18 to 60 years in age) were divided into two groups: cases with simple non-alcoholic fatty liver (NAFL, n = 11) and cases with NASH (n = 40). All subjects underwent physical examination and anthropometric measurements. Fasting serum was assayed by blood biochemistry. Insulin resistance was estimated by the homeostatic model assessment index (HOMA-IR). Serum levels of high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) were detected by enzyme-linked immunosorbent assay. Carotid intima-media thickness (CIMT) was estimated by carotid ultrasound. Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index were estimated using a volume-plethysmographic apparatus. Data for the two groups were summarized as mean +/- SD or interquartile range and intergroup differences were evaluated by paired t-test or Wilcoxon test, with two-sided P-values less than 0.05 indicating significance.

RESULTSThe serum levels of hs-CRP, sICAM-1, and ET-1 were significantly higher in the NASH group than the NAFL group (all P less than 0.001). In addition, the CIMT and baPWV were significantly higher in the NASH group than the NAFL group (both P less than 0.05). The HOMA-IR was also significantly higher in the NASH group than the NAFL group (P less than 0.001).

CONCLUSIONLiver inflammation and insulin resistance may play important, and possibly collaborative, roles in promoting arterial endothelial dysfunction and atherosclerosis in NAFLD patients. NASH patients, especially those who are young and middle-aged, may benefit from early monitoring and prevention strategies to help decrease the risk of developing severe cardiovascular diseases.

Adolescent ; Adult ; Atherosclerosis ; pathology ; C-Reactive Protein ; metabolism ; Carotid Arteries ; diagnostic imaging ; Carotid Intima-Media Thickness ; Endothelin-1 ; blood ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Intercellular Adhesion Molecule-1 ; blood ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; blood ; diagnostic imaging ; Young Adult