OBJECTIVE: To establish RP-HPLC method for the determination of fluconazole in human plasma.METHODS: After liquid-liquid extraction,the plasma sample was analyzed on Diamonsil C18 column with column temperature set at room temperature.The mobile phrase consisted of methanol-0.07% aqueous solution of triethylamine(50∶ 50) with a flow rate of 1mL? min-1.The UV detection wavelength was set at 210nm,and phenacetin was used as the internal standard.RESULTS: The linear range of fluconazole was 0.15～ 10.0mg? L-1(r=0.999 2),with lower quantification limit at 0.15mg? L-1.The intra-day RSD was between 3.37% and 7.48% and the inter-day RSD was between 7.03% and 12.05%;the method recovery was 103.64%(RSD=5.04%),and the average extraction recovery was between 83.81%(RSD=5.77%).CONCLUSION: This method was sensitive,accurate,rapid and reproducible,and suitable for the content determination of fluconazole in plasma.

Objective To observe diffusion changes of epiphysis of femoral head with ischemia of difference phases by line-scan diffusion weighted imaging(LSDWI),and determine whether LSDWI can provide temporal information and severity about ischemia of epiphysis.Methods lschemia was surgically induced in one hip of each piglet(n=25)and the other hip served as a normal control.Piglets were imaged before surgery and at 3 hours,72 hours and 1,3 and 6 weeks after surgery by using LSDWI.Apparent difrusion coefficients(A DC)in epiphysis of the femoral heads were calculated.Significant difierences in ADC values between ischemia group and control group were found by using paired t-test.After scan at individual time points,5 piglets were sacrificed for histological study each time.Results The ADC value in the ischemic femoral heads f(1.22±0.37)×10-3 mm2/s]decreased significantiy at 3 hours after surgery (t=3.914,P＜0.01),compared to that in control[(1.73±0.33)×10-3mm2/s},and increased at 72 hours[(2.15±0.32)×10-3mm2/s versus(1.70±0.22)×10-3 mm2/s](t=3.348,P＜0.01).Then ADC valne kept increasing until 6 weeks after surgery[(1.61±0.27)×10-3mm2/s in ischemia side vs (1.11±0.45)×10-3mm2/s in the control](t=4.136,P＜0.01).rrhe percentage change of the ADC value significandy increased at 3 hours,72 hours,1 and 3 week(s)after the surgery(P＜0.01),compared to that at the prior neighboring time point.No significant increase in the percentage change of ADC value was found between the 3rd week and the 6th week after the surgery(t=2.29.P＞0.05).Histological examinations revealed abnormal thickening within epiphyseal cartilage,and cartilaginous islands within ossified tissues.Growth disturbante wag found in form of focal growth plate disruption.Conclusions Dynamic changes of ADC values were found with the prolonged ischemia of the femoral head by LSDWI.It could serve as a useful marker for evaluating duration and extent of ischemic epiphyseal disruption.

Objective To explore the remodeling modes and the plaque distribution of atherosclerotic BA at 3.0T high resolution MRI.Methods 90 symptomatic patients with atherosclerotic stenosis of BA on digital subtraction angiography (DSA) (50 ％-99 ％) were recruited consecutively.Luminal area,vessel area of maximal narrow sites and the reference sites were measured.The differences of involved imaging parameters between negative group and positive group were analyzed.Results 51 patients with required imaging quality were enrolled finally.Among the 51 patients,the rate of positive remodeling cases was 72.5％ (37/51) and negative remodeling took over 27.5％ (14/51).Compared with the negative remodeling group,the positive remodeling group had greater plaque size,larger plaque burden percentage,and higher maximal wall thickness at maximal lumen narrowing sites.The plaques were mainly located at ventral wall of the vessel.Conclusion 3.0T high-resolution MR imaging could be applied in assessing the remodeling modes and plaque distribution of BA stenosis.

This study was aimed to prepare the spraying agent of prescriptions of Miao nationality herb and investigate the effect of Miao nationality herbs spray for serum SOD, MDA, and expression of Fas and Caspase-3 mRNA in lung tissues of silica-treated rats. The healthy SD rats were divided into 5 groups. Silica dust suspension was used in the model establishment of 4 groups. After the model was successfully established, 3 groups were randomly selected and given glucocorticoids atomization inhalation, Miao nationality herbs spray, Miao nationality herbs spray combined with intragastric administration of herbal medicine, respectively. After 40-day treatment, water-solubletetrazolium salt (WST-1) was used in the detection of serum superoxide dismutase (SOD). Thiobarbituric acid (TBA) was used in the detection of malondialdehyde (MDA). The mRNA expression variance of the Fas and Caspase-3 were detected by RT-PCR. The results showed that compared with the silica dust suspension group, the SOD activity of serum in the Miao nationality herbs spray group was significantly increased (P< 0.05). MDA content and the mRNA of Fas and Caspase-3 were significantly lower in the Miao nationality herbs spray group (P< 0.05). It was concluded that Miao nationality herbs spray group was able to increase the SOD activity of serum, decrease MDA content, and obviously decrease the expression of Fas and Caspase-3 of lung tissues among silica dust suspension rats.

Objective To investigate the ability of quantitative radiomic method based on highresolution magnetic resonance imaging (HR-MRI) to distinguish between culprit plaques and non-culprit plaques of intracranial atherosclerosis.Methods Patients with middle cerebral artery and basilar artery stenosis underwent HR-MRI in Changhai Hospital Affiliated to the Naval Medical University from September 2013 to October 2016 were analyzed retrospectively.The minimum lumen area,plaque burden,severity of luminal stenosis,intraplaque hemorrhage (IPH),enhancement rate,and 109quantitative radiomic characteristics of the culprit and non-culprit plaques were measured.For clinical features and traditional plaque morphology,multivariate logistic regression models were used to determine independent risk factors for culprit plaque.A random forest-supervised machine learning method was used to determine the radiomic characteristics of distinguishing between symptomatic plaques and asymptomatic plaques.The receiver operating characteristic (ROC) curve was constructed,and the diagnostic efficacy was described by the area under the curve (AUC).Results During the study,158 subjects were enrolled,and they aged (59.42± 11.62) years.The plaques of 75 patients were located in middle cerebral artery,and the plaques of 83 patients were located in basilar artery.There were 111 symptomatic patients and 47 asymptomatic patients.Multivariate logistic regression analysis showed that smoking (odds ratio [OR] 2.724,95％ confidence interval [CI] 1.200-6.183),IPH (OR 11.340,95％ CI 1.441-89.221),and enhancement rate (OR 6.865,95％ CI 1.052-44.802) were the independent risk factors for culprit plaques.The AUC of these three characteristics for predicting symptomatic plaques were 0.605,0.584,and 0.590,respectively.The combination of the three cloud improve the test efficacy for the intracranial atherosclerotic culprit plaques,AUC could reached 0.714.Radiomic analysis showed that 22 radiomic characteristics extracted from T-2 weighted imaging,T1 weighted imaging,and contrast-enhanced T1 weighted imaging were associated with the culprit plaques.Their AUCs were 0.801,0.835,and 0.846,respectively.After the combination of all morphological and radiomic characteristics,AUC could reach 0.976,the accuracy rate was 87.4％.However,the difference was not statistically significant compared to the combined AUC of all radiomic characteristics (0.953) (P=0.275).Conclusion Radiomic analysis could accurately distinguish between the culprit plaques and non-culprit plaques of intracranial atherosclerosis,and is superior to the traditional morphological methods.

Objective:To explore the application situation and hotspots of the Q method in the field of nursing research and provide a reference for the nursing workers in China to learn and apply the Q method.Methods:Literature retrieval was conducted based on Web of Science, and statistical analysis was conducted on the number of articles published, countries, journals, institutions, authors, highly cited papers, research directions and high-frequency co-occurrence words by using the analysis function of Web of Science and visual imaging of VOSviewer.Results:A total of 686 authors from 25 countries and 23 institutions published 326 papers in 157 journals applying the Q method in nursing research, showing an overall increasing trend. South Korea (12.27%) , the United States (7.98%) , the United Kingdom (7.06%) ranked the highest number of articles published, and China ranked the sixth (3.68%) The number of citations per article was the highest in the United Kingdom (33.78 times) , followed by Canada (19.67 times) . Psychology and health care were the most interdisciplinary subjects. The research hotspots expanded from methodological discussions to nursing education, clinical practice, psychological nursing and health promotion.Conclusions:Q method is still in its infancy in the field of nursing in China and has not been widely promoted and practiced. China's publication volume and influence are relatively weak. In the future, international exchanges and cooperation should be expanded and academic frontiers and research hotspots should be grasped to improve the level and quality of research.

Objective:To explore the value of 3.0 T high resolution MRI (HR-MRI) in the follow-up of drug treatment in acute and non-acute ischemic stroke caused by middle cerebral artery (MCA) plaque.Methods:The perspective study enrolled patients with ischemic stroke caused by MCA stenosis from October 2012 to October 2015 in the department of Neurology and Neurosurgery of Changhai Hospital Affiliated to Naval Medical University. All the patients underwent HR-MRI and then were divided into acute and non-acute stroke groups according to the intervels of the last symptom onset to the time of HR-MRI examination. All patients were informed consent to receive antiplatelet drug and intensive lipid therapy and followed up with HR-MRI. The HR-MRI sequence including T 2WI, T 1WI and contrast-enhanced T 1WI of vessel wall, and T 2WI and DWI of brain were routinely performed. T-test of paired samples was used to evaluate the changes of stenosis rate of vascular lumen, plaque enhancement degree, plaque volume and plaque burden on HR-MRI, and the NIHSS score of nervous system and blood biochemical indicators of the patients before and after treatment. Chi square test was used to compare the difference in ischemic event recurrcence between the acute and the non-acute stroke group. Results:A total of 31 acute stroke patients and 20 non-acute stroke patients were enrolled in the study. The mean follow-up time of acute stroke group was (671.71±522.86) days. Compare with the baseline, the stenosis rate of vascular lumen ( P=0.039), plaque enhancement degree ( P<0.001), plaque volume ( P=0.024) and plaque burden ( P=0.031) were all improved after the drug treatment, the NIHSS score of nervous system was also significantly improved, and the levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in 12 patients were significantly decreased. The mean follow-up time of patients with non-acute stroke was (695.35±555.90) days. The stenosis rate of vascular lumen, plaque enhancement degree, plaque volume and plaque burden were slightly improved, but without statistical significance ( P>0.05). There were no significant changes in NIHSS score of nervous system, TC, triglyceride (TG) and LDL-C ( P>0.05), however the high density lipoprotein cholesterol (HDL-C) was significantly increased than that in the baseline ( P=0.02). During the follow-up period, no new cerebral infarction was found in the DWI images of the two groups. Six patients had transient ischemic attack (TIA) recurrence in the acute stroke group and 5 patients in the non-acute stroke group, there was no significant difference between both groups(χ 2=0.229, P= 0.632). Conclusion:HR-MRI can be used as an important evaluation method for the follow-up of MCA atherosclerotic plaque therapy. After antiplatelet therapy and intensive lipid-lowering therapy, the plaque volume and burden of MCA offending plaque, and plaque enhancement decreased in acute stroke patients but there was no significant change in non-acute patients.

Objective: To build risk prediction models for acute kidney injury (AKI) in severely burned patients, and to compare the prediction performance of machine learning method and logistic regression model. Methods: The clinical data of 157 severely burned patients in August 2nd Kunshan factory aluminum dust explosion accident conforming to the inclusion criteria were collected. Patients suffering AKI within 90 days after admission were enrolled in group AKI, while the others were enrolled in non-AKI group. Single factor analysis was used to choose independent factors associated with AKI, including sex, age, admission time, features of basic injuries, initial score on admission, treatment condition, and mortality on post injury days 30, 60, and 90. Data were processed with Mann-Whitney U test, chi-square test, and Fisher′s exact test. Variables with P<0.1 in single factor analysis and those with possible clinical significance were brought into the establishment of prediction model. Logistic regression and XGBoost machine learning algorithm were used to build the prediction model of AKI. The area under receiver operating characteristic curve (AUC) was calculated, and the sensitivity and specificity for optimal threshold value were also calculated for each model. Nonparametric resampling test was used to compare the significance of difference of AUC of the two models. Results: (1) Eighty-nine (56.7%) patients developed AKI within 90 days from admission. Compared with 68 patients in non-AKI group, 89 patients in group AKI were older (Z=-2.203, P<0.05), with larger total burn area and full-thickness burn area (Z=-5.200, -6.297, P<0.01), worse acute physical and chronic health evaluation (APACHE) Ⅱ score, abbreviated burn severity index score, and sequential organ failure assessment (SOFA) score on admission (Z=-7.485, -4.739, -4.590, P<0.01), higher occurrence rate of sepsis (χ²=33.087, P<0.01), higher rates of accepting tracheotomy, mechanical ventilation, and continuous renal replacement therapy (χ²=12.373, 17.201, 43.763, P<0.01), larger first excision area (Z=-2.191, P<0.05), and higher mortality on post injury days 30, 60, and 90 (χ²=7.483, 37.259, 45.533, P<0.01). There were no statistically significant differences in sex, open decompression, admission time, 24-hour fluid volume after admission, 48-hour fluid volume after admission, the first 24-hour urine volume, the second 24 hour urine volume, the first excision time, and inhalation injury (χ²=0.529, 3.318, Z=-1.746, -0.016, -1.199, -1.824, -0.625, -1.747, P>0.05). The rates of deep vein catheterization of patients in the two groups were both 100%. (2) There were twenty possible prediction variables for preliminary establishment of model according to the difference results of single factor analysis and clinical significance of variables. (3) The logistic regression prediction model had three variables: APACHE Ⅱ score [odds ratio (OR)=1.36, 95% confidence interval (CI)=1.20-1.53, P<0.001], sepsis (OR=2.63, 95% CI=0.90-7.66, P>0.05), and the first 24-hour urine volume (OR=0.71, 95% CI=0.50-1.01, P>0.05). The AUC of the logistic regression prediction model was 0.875 (95% CI=0.821-0.930), with the specificity and sensitivity of optimal threshold value 84.4% and 77.7%, respectively. (4) XGBoost machine learning model had seven main predictive variables: APACHE Ⅱ score, full-thickness burn area, 24-hour fluid volume after admission, sepsis, the first 24-hour urine volume, SOFA score, and 48-hour fluid volume after admission. The AUC of machine learning model was 0.920 (95% CI=0.879-0.962), higher than that of logistic regression model (P<0.001), with the specificity and sensitivity of optimal threshold value 89.7% and 82.0%, respectively. Conclusions Sepsis and fluid resuscitation are two important predictive variables that can be intervened for AKI in severely burned patients. Machine learning method has a better performance and can provide more accurate prediction for individuals than logistic regression prediction model, and therefore has good clinical application prospect.

Ferroptosis is closely associated with the progression of various diseases.There are a series of anti-ferroptosis systems in the cell,the main function of which is to eliminate lipid peroxides and inhibit the occurrence of ferropto-sis.Ubiquitination is a crucial type of post-translational protein modification which can influence the degradation,intracellular localization,or function of substrate proteins.Ubiquitination modification plays an important role in regulating key proteins in-volved in ferroptosis pathways,such as SLC7A11,GPX4,FSP1,iron metabolism-related proteins,and other critical proteins in ferroptosis pathways.This review aims to summarize the research progress on ubiquitination modification of these key proteins in ferroptosis pathways,thereby elucidating the specific role of ubiquitination in ferroptosis pathways.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.