Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the microcirculatory perfusion of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.Methods:This study was an experimental study. Thirty-two male big ear white rabbits aged 6-8 months were assigned into electric burn group of 20 rabbits with high-voltage electric burns in the right lower limb and control group of 12 rabbits with sham injury in the right lower limb using the random number table method. At 0.5, 24.0, 48.0, and 72.0 h post injury, the lower limbs of rabbits in the two groups underwent axial fast spin echo T1-weighted imaging, fast spin echo T2-weighted imaging, and DCE-MRI examination. A reference region-based hemodynamic model was applied to obtain the blood perfusion parameters of skeletal muscle in the injured limbs, including the volume transfer constant K trans value and rate constant K ep value. The skeletal muscle tissue from the electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury and the control group of rabbits at 0.5 h post injury was harvested for immunohistochemical staining to observe the microvascular changes and calculate the microvascular density (MVD). The correlation between the K trans and K ep values and the MVD of skeletal muscle tissue in electric burn group of rabbits at 0.5-72.0 h post injury was analyzed. The number of samples was 5 in the electric burn group, and the number of samples was 3 in the control burn group. Results:From 0.5-72.0 h post injury, the K trans and K ep values in skeletal muscle tissue of electric burn group of rabbits exhibited the trends of increase first and decrease then, both of which reached peak values at 24.0 h post injury. The K trans values at 0.5, 24.0, 48.0, and 72.0 h post injury (with t values of -15.77, -14.91, -40.35, and -40.25, respectively, P<0.05) and the K ep values at 0.5, 24.0, and 48.0 h post injury (with t values of -5.39, -6.82, and -6.83, respectively, P<0.05) in skeletal muscle tissue in electric burn group of rabbits were significantly higher than those in control group. The MVD in skeletal muscle tissue in control group of rabbits at 0.5 h post injury and in electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury was (24.7±3.5), (21.8±2.2), (40.8±9.1), (16.4±2.4), and (9.8±0.8) per mm2, respectively. The MVD in skeletal muscle tissue in electric burn group of rabbits at 24.0 h post injury was significantly higher than that in control group at 0.5 h post injury ( t=2.89, P<0.05), and the MVD in skeletal muscle tissue at 48.0 and 72.0 h post injury was significantly lower than that in control group at 0.5 h post injury (with t values of 4.01 and 9.52, respectively, P<0.05). The K trans and K ep values of skeletal muscle tissue in rabbits in electric burn group were significantly positively correlated with microvascular density at 0.5 to 72.0 h post injury (with both r values of 0.95, P<0.05). Conclusions:The quantitative perfusion parameters K trans and K ep values of DCE-MRI can effectively reflect the microcirculatory perfusion changes of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To explore the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the microcirculatory perfusion of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.Methods:This study was an experimental study. Thirty-two male big ear white rabbits aged 6-8 months were assigned into electric burn group of 20 rabbits with high-voltage electric burns in the right lower limb and control group of 12 rabbits with sham injury in the right lower limb using the random number table method. At 0.5, 24.0, 48.0, and 72.0 h post injury, the lower limbs of rabbits in the two groups underwent axial fast spin echo T1-weighted imaging, fast spin echo T2-weighted imaging, and DCE-MRI examination. A reference region-based hemodynamic model was applied to obtain the blood perfusion parameters of skeletal muscle in the injured limbs, including the volume transfer constant K trans value and rate constant K ep value. The skeletal muscle tissue from the electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury and the control group of rabbits at 0.5 h post injury was harvested for immunohistochemical staining to observe the microvascular changes and calculate the microvascular density (MVD). The correlation between the K trans and K ep values and the MVD of skeletal muscle tissue in electric burn group of rabbits at 0.5-72.0 h post injury was analyzed. The number of samples was 5 in the electric burn group, and the number of samples was 3 in the control burn group. Results:From 0.5-72.0 h post injury, the K trans and K ep values in skeletal muscle tissue of electric burn group of rabbits exhibited the trends of increase first and decrease then, both of which reached peak values at 24.0 h post injury. The K trans values at 0.5, 24.0, 48.0, and 72.0 h post injury (with t values of -15.77, -14.91, -40.35, and -40.25, respectively, P<0.05) and the K ep values at 0.5, 24.0, and 48.0 h post injury (with t values of -5.39, -6.82, and -6.83, respectively, P<0.05) in skeletal muscle tissue in electric burn group of rabbits were significantly higher than those in control group. The MVD in skeletal muscle tissue in control group of rabbits at 0.5 h post injury and in electric burn group of rabbits at 0.5, 24.0, 48.0, and 72.0 h post injury was (24.7±3.5), (21.8±2.2), (40.8±9.1), (16.4±2.4), and (9.8±0.8) per mm2, respectively. The MVD in skeletal muscle tissue in electric burn group of rabbits at 24.0 h post injury was significantly higher than that in control group at 0.5 h post injury ( t=2.89, P<0.05), and the MVD in skeletal muscle tissue at 48.0 and 72.0 h post injury was significantly lower than that in control group at 0.5 h post injury (with t values of 4.01 and 9.52, respectively, P<0.05). The K trans and K ep values of skeletal muscle tissue in rabbits in electric burn group were significantly positively correlated with microvascular density at 0.5 to 72.0 h post injury (with both r values of 0.95, P<0.05). Conclusions:The quantitative perfusion parameters K trans and K ep values of DCE-MRI can effectively reflect the microcirculatory perfusion changes of skeletal muscle in rabbit limbs in the early stage after high-voltage electric burns.

Objective To construct a risk prediction score model for serious adverse event (SAE) after cardiac catheterization in patients with adult congenital heart disease (ACHD) and pulmonary hypertension (PH) and verify its predictive effect. Methods The patients with PH who underwent cardiac catheterization in Wuhan Asian Heart Hospital Affiliated to Wuhan University of Science and Technology from January 2018 to January 2022 were retrospectively collected. The patients were randomly divided into a model group and a validation group according to the order of admission. The model group was divided into a SAE group and a non-SAE group according to whether SAE occurred after the catheterization. The data of the two groups were compared, and the risk prediction score model was established according to the results of multivariate logistic regression analysis. The discrimination and calibration of the model were evaluated using the area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test, respectively. Results A total of 758 patients were enrolled, including 240 (31.7%) males and 518 (68.3%) females, with a mean age of 43.1 (18.0-81.0) years. There were 530 patients in the model group (47 patients in the SAE group and 483 patients in the non-SAE group) and 228 patients in the validation group. Univariate analysis showed statistical differences in age, smoking history, valvular disease history, heart failure history, N-terminal pro-B-type natriuretic peptide, and other factors between the SAE and non-SAE groups (P<0.05). Multivariate analysis showed that age≥50 years, history of heart failure, moderate to severe congenital heart disease, moderate to severe PH, cardiac catheterization and treatment, surgical general anesthesia, and N-terminal pro-B-type natriuretic peptide≥126.65 pg/mL were risk factors for SAE after cardiac catheterization for ACHD-PH patients (P<0.05). The risk prediction score model had a total score of 0-139 points and patients who had a score>50 points were high-risk patients. Model validation results showed an area under the ROC curve of 0.937 (95%CI 0.897-0.976). Hosmer-Lemeshow goodness-of-fit test: χ2=3.847, P=0.797. Conclusion Age≥50 years, history of heart failure, moderate to severe congenital heart disease, moderate to severe PH, cardiac catheterization and treatment, general anesthesia for surgery, and N-terminal pro-B-type natriuretic peptide≥126.65 pg/mL were risk factors for SAE after cardiac catheterization for ACHD-PH patients. The risk prediction model based on these factors has a high predictive value and can be applied to the risk assessment of SAE after interventional therapy in ACHD-PH patients to help clinicians perform early intervention.

Malnutrition is relatively common in patients with cardiovascular diseases and is closely related to the poor prognosis of the disease. This article reviewed the main contents and application status, advantages and disadvantages of various nutritional assessment tools for the patients with cardiovascular diseases to provide the basis for healthcare professionals to select the appropriate nutritional assessment method of patients with cardiovascular diseases, identify their malnutrition as early as possible, and implement targeted nutritional interventions.

Objective To observe the value of apparent diffusion coefficient(ADC)for quantitatively evaluating progressive muscle injury of rabbit limbs in early stage of high-voltage electrical burn.Methods Twenty healthy adult rabbits were selected to establish limb high-voltage electrical burn models,which were randomly divided into 0.5,24,48 and 72 h groups(each n=5).MR diffusion weighted imaging(DWI)was collected for each group at 0.5,24,48 and 72 h after modeling,and the injured core muscles of the right hind limb and the normal muscles of the contralateral limb were taken for HE staining.The muscle's ADC,muscle fiber density(MFD)and muscle fiber diameter(D)values at the injured core of current entry and exit were compared,and those of normal muscle were also analyzed.The correlations of ADC values in injured core muscle and MFD or D values were investigated.Results There were significant differences of ADC values of injured core muscle at both the entry and exit and normal muscle,also of ADC values of injured core muscle at the entry and exit within each group(all P＜0.05).ADC values of injured core muscle at the entry and exit decreased with time going(all P＜0.05),but ADC values of normal muscle were not significantly different among different time points(P＞0.05).MFD values of injured core muscle at the entry and exit decreased with time going(all P＜0.05),while MFD values of the normal muscle,D values of the injured core muscle at the entry and exit and normal muscle were not significantly different among time points(all P＞0.05).ADC value of the injured core muscle was positively correlated with MFD value and negatively correlated with D value(rs=0.846,r=-0.507,both P＜0.05).Conclusion ADC could quantitatively evaluate the progressive muscle injury of rabbit limbs in early stage of high-voltage electrical burn.

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

Objective:To investigate the role of chloroquine (CQ) during inducing the death of hepatic carcinoma cells and to explore the clinical application of autophagy‐related agents .Methods:Three kinds of hepatic carcinoma cell lines were chosen and treated with CQ at different concentrations for 24 hours .Then MTT assay was applied to determine the proliferation ,and prodium iodide (PI) stalning assay was used to detect the cell death .The specific apoptosis was examined by Hochest 33342 stalning , TUNEL stalning and Western blotting (caspase‐9 ) . The autophagic function was explored by GFP‐LC3 redistribution ,Western blotting (LC3) ,and electron microscopy .Results:MTT assay revealed that the proliferation of hepatic carcinoma cells was significantly inhibited by using CQ for 24 hours .The PI‐positive cells increased significantly after the treatment with CQ (≥ 20 μmol/L) .Hochest33342 stalning assay showed karyopyknosis and karyorrhexis .Meanwhile , TUNEL positive cells significantly increased and caspase‐9 was activated .However ,there was no significant change in the number of PI‐positive cells after the CQ treatment at concentrations of 5 μmol/L and 10 μmol/L .CQ treatment resulted in significant increase of GFP‐LC3‐positive cells and expression of LC3‐II .When the caspase inhibitor Z‐VAD‐FMK and 3‐MA or Atg5 siRNA were applied at the same time , 40 μmol/L CQ‐induced M HCC97‐L cell death was significantly inhibited . Conclusions:CQ can inhibit the autophagic degradation of hepatic carcinoma cells , and resulted in the accumulation of autophagosomes and autophagic proteins .High‐dose CQ directly induces the death of hepatic carcinoma cells ,and the death has both characteristics of apoptosis and autophagic death .

Chronic hepatitis C virus (HCV) infection has become a major public health burden worldwide. Twenty-two sophocarpinic acid or matrine derivatives were synthesized and their anti-HCV activities were evaluated in vitro. The structure-activity analysis revealed that (i) sophocarpinic acids with a D-seco 3-ring structure scaffold were more favorable than matrines with a 4-ring scaffold; (ii) the introduction of an electron-withdrawing group on the phenyl ring in 12-N-benzenesulfonyl Δ (βγ) sophocarpinic acids was beneficial for the antiviral activity against HCV. Among them, compounds 9h and 9j exhibited the most potent inhibitory activities on HCV replication with selectivity indies of 70.3 and 30.9, respectively. Therefore, both were selected as antiviral candidates for further investigation.