OBJECTIVE To establish a method for determining the content of 11 antioxidants and their degradation products in recombinant Exendin-4-FC fusion protein injection by HPLC. METHODS The protein was precipitated with saturated ammonium sulfate. After centrifugation, the supernatant was transferred to a C18 solid phase extraction cartridge activated by methanol. Then the cartridge was eluted with 4 mL of methanol and 5 mL of ethyl acetate respectively, and the eluent was diluted with methanol-ethyl acetate(2∶3) mixed solvent and passed through a 0.22 µm PTFE hydrophobic filter. It was analyzed by HPLC and quantified by external standard method. Chromatographic conditions: Kinetex® XB-C18 100Å (100 mm×4.6 mm, 2.6 µm)column, the detection wavelength was 230 nm, the column oven was 30 ℃, the injection volume was 5 µL and the flow rate was 0.4 mL·min–1, mobile phase was 0.1% formic acid-methanol(A)-0.1% formic acid aqueous solution(B), the running time was 45 min. RESULTS The 11 target substances showed a good linear relationship in the range of 2.5−35 μg·mL–1 with R2 ≥0.99. At three different concentration(25, 10, 5 μg·mL–1) of spiked samples, the average recovery rates of 11 antioxidants ranged from 88.1% to 106.5%, with RSDs in the range of 0.10%–9.05%. The RSDs of 6 repeatable samples was 2.01%–4.77%, which of 12 intermediate precision samples was 2.58%–9.75%. The positive/inverted samples of three batches of recombinant Exendin-4-FC fusion protein injection were detected at 0 month, 3 months and 6 months(25 ℃), and the results showed that there was no antioxidant and its degradation leaching in all batches of samples at different detection points. CONCLUSION The method has good specificity, high accuracy and precision, good solution stability, high durability and can be used for the content detection of antioxidants in drugs.

Objective:To establish a prediction model for symptomatic radiation pneumonitis (SRP) after radiotherapy for thoracic cancer based on a longitudinal cohort and dose interval variations.Methods:Clinical data of 587 patients who received thoracic radiotherapy in Department of Radiotherapy of Yunnan Cancer Hospital from July 2022 to June 2023 were retrospectively analyzed. The National Cancer Institute common terminology criteria for adverse events (CTCAE) version 5.0 was used to grade radiation pneumonitis, and clinical factors, traditional independent dosimetric characteristics and dose interval variation characteristics were collected. Features used to predict the occurrence of SRP were screened using genetic algorithms and analyzed the correlation between the selected features and SRP occurrence. Predictive models for SRP occurrence were established using the selected features and evaluated, and the optimal predictive model was visualized using a column chart.Results:The incidence of SRP was 35.94%. Five clinical factors, seven independent dosimetric features and six dose interval variation features were screened out by genetic algorithms to effectively predict the occurrence of SRP. The area under ROC curve (AUC) of clinical factors combined with traditional independent dosimetric factors and dose interval variation factors was 76%. The AUC of clinical factors combined with traditional independent dosimetric factors and that of clinical factors combined with dose interval variation factors was 69% and 67%, respectively. The addition of the characteristics of dose interval variation factors significantly improved the effectiveness of the prediction model.Conclusions:The supplement of the characteristics of dose interval variation factors can significantly improve the performance of the SRP prediction model for thoracic tumors after radiotherapy. The SRP prediction model based on dose interval variations can effectively predict the occurrence of SRP.

Objective : To investigate the protective effect and related mechanisms of dexmedetomidine (Dex) on iron overload toxicity in mouse hippocampal neurons (HT22) induced by ferric ammonium citrate (FAC) . Methods: Selected HT22 cells in good condition were randomly divided into 4 groups: control group ( Ctrl group), FAC treatment group (FAC group), Dex treatment group (Dex group), ferroptosis inhibitor Fer⁃1 treatment group (Fer1 group) . The iron overload model was established by FAC⁃induced cells . Subsequently, the proliferation and survival rate of HT22 cells was detected by CCK⁃8 method; Western blot was used to detect the ferroptosis marker proteins prostaglandin⁃endoperoxide synthase 2 ( PTGS2 ) and acyl⁃CoA synthetase long⁃chain family member 4 (ACSL4) . The protein expressions of mammalian target of rapamycin ( mTOR), transferrin receptor 1 ( TFR1) and ferroportin (Fpn); the gene expression levels of PTGS2 and ACSL4 in HT22 cells were detected by qPCR; Reactive oxygen species (ROS) levels in HT22 cells was detected by DHE fluorescent probe; MDA detection kit was used to detect lipid oxidation levels in HT22 cells; Mito⁃FerroOrange—ferrous ion probe was used to detect ferrous ion levels in HT22 cells; electron microscopy was used to detect intracellular ultrastructural changes . Results: Dex group and Fer⁃1 group significantly decreased cell death rate after 2 h of pretreatment, the protein and gene expression levels of ferroptosis markers PTGS2 and ACSL4 significantly decreased . The degree of cell ultrastructural damage was significantly improved . The levels of ROS, lipid oxidation and Fe2 + were significantly lower than those of the FAC group (P < 0. 05) . Conclusion Dex pretreatment can attenuate FAC⁃induced iron overload toxicity in⁃ jury in HT22 cells, which may be related to the inhibition of ferroptosis .

Objective:To explore the effect of different teaching modes in medical students′education of cardiopulmonary resuscitation(CPR)skills.Methods:One hundred and fifty college students were randomly allocated to classroom teaching group(G1=50), problem-based learning(PBL)group(G2=50) and computer-based teaching group(G3=50)from March to December in 2019.The students′acquisition and retention of theoretical knowledge and skills were assessed before(baseline)and after the teaching(immediately), then 2 months and 6 months later.Results:One hundred and fifty college students participated in the study.Among them, 84(56.0%)were male, with an average age of 23 years old.Sixteen students(10.7%)had participated in similar CPR training.There was no significant statistical difference in the demographic characteristics of students among three groups.At four time points including baseline, after teaching(immediately), 2 months and 6 months later, there was no significant difference in the theoretical examination results among three groups( P>0.05). But after teaching, the scores of each group were improved.At the second time point(after teaching immediately), each group had the highest scores( P<0.05). Compared the scores of the second point, the ones of the third time point(2 months later after teaching)and the fourth time point(6 months later after teaching)decreased, but there was no significant difference between the two time points( P<0.05). There was no significant difference in the pass rates of skill exam at the time point of baseline among three groups( P>0.05). The pass rates of G2 and G3 were significantly higher than those of G1 at 2 and 6 months later after teaching( P<0.05), but there was no significant difference between two groups.After teaching, the passing rate of each group was significantly higher than that of the baseline, and there were significant differences in the passing rates of any other time points after teaching, with the passing rate decreasing.Students′ feedback showed that all of them could clearly understand the teaching objective and accept the difficulty of the course, and PBL and computer teaching modes were more acceptable. Conclusion:PBL and computer-based teaching modes have better learning effectiveness and acceptance, which can be used as supplemental training to conventional classroom teaching or as strategies to consolidate learning.Two months may be the time point for retraining.

Objective:To study the clinical prognosis and related factors affecting optimal medical therapy (OMT) compliance of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).Methods:A prospective study was conducted to select 3 818 patients who were diagnosed with CAD and successfully underwent PCI in TEDA International Cardiovascular Hospital from October 2016 to September 2017. The clinical information and application of OMT during hospitalization and 1 year later were collected for research.The patients were divided into OMT group and non OMT group according to whether they adhered to OMT during follow-up one year after discharge. After comparing the imbalance baseline data of hypertension,diabetes and hyperlipidemia with propensity score,demographic characteristics, coronary revascularization history, CAD, laboratory related laboratory examinations,and the use of OMT drugs were compared between the two groups. Cox regression model was used to analyze the relationship between long-term OMT and clinical prognosis in patients with CAD.Multivariate binary logistic regression was used to analyze the related factors affecting long-term OMT compliance.Results:A total of 3 818 cases of CAD patients were matched by propensity score and 2 596 patients were included in the study. There were 1 609 males and 987 females. The age was (62.51±9.56) years old.One year later,1298 patients (50%) insisted on OMT,including dual antiplatelet therapy(DAPT), statins, β-blockers and ACEI/ARB were 97.0% (2 517/2 596),94.5%(2 454/2 596),69.6% (1 806/2 596) and 64.2% (1 666/2 596), especially angiotensin converting enzyme inhibitors / angiotensin receptor blockers and β Receptor blockers decreased the most.Cox regression analysis showed that after adjusting for other factors, compared with non-adherence to OMT group,OMT after PCI was associated with better prognosis ( HR=0.416,95% CI 0.270-0.641, P<0.001). The prognosis of CAD patients with history of old myocardial infarction ( HR=1.804,95% CI 1.070-3.041, P=0.027),cardiac insufficiency ( HR=2.074,95% CI 1.161-3.702, P=0.014),multivessel coronary disease ( HR=2.211,95% CI 1.228-3.983, P=0.008) and BMI>24 ( HR=1.570,95% CI 1.037-2.377, P=0.033) were related to worse clinical outcomes. Multi-factor binary Logistic regression showed that OMT at hospitalization was a strong influencing factor of long-term adherence to OMT ( OR=41.278,95% CI 29.961-56.871, P<0.001). Patients with higher education,employee medical insurance and with history of PCI tend to persist in OMT. Conclusion:The medication compliance of patients with long-term OMT after PCI is still poor,while the high compliance of OMT is related to the lower incidence of adverse cardiovascular events,including death, nonfatal myocardial infarction and stroke. If there is no obvious contraindication,all patients after PCI should adhere to OMT.

Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy. Among vascular coagulation agents, the extracellular domain of coagulation-inducing protein tissue factor, truncated tissue factor (tTF), is the most widely used. Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation, free tTF cannot be used for cancer treatment on its own but must be combined with other moieties. We here developed a novel, tumor-specific tTF delivery system through coupling tTF with the DNA aptamer, AS1411, which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells. Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors, thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects. This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.

Objective:To summarize the effect of Chinese Children′s Cancer Group (CCCG) Wilms tumor (WT)-2015 protocol.Methods:This was a prospective study. CCCG-WT-2015 protocol was revised on the basis of the CCCG-WT-2009 protocol. Clinical data of 288 children diagnosed with newly diagnosed kidney neoplasms in fourteen pediatric centers between September 2015 to December 2018 were summarized. The age of onset, distribution of pathological subtypes, staging, curative effect and prognostic factors of these children were analyzed. Kaplan-Meier method was used for survival curve and Log-Rank method was used for univariate analysis.Results:Among 288 cases with kidney neoplasms, there were 261 cases of WT, including 254 cases (97.3%) with favorable histology (FH) WT and 7 cases (2.7%) with unfavorable histology WT (UFHWT). The 3 year events free survival (EFS) rate for FHWT and UFHWT were (88.9±2.1)% and (80.0±17.9)%, which were better than that in WT-2009 (81.2% and 71.7%). In the 96 cases of stage Ⅲ/Ⅳ FHWT with indications for radiotherapy, 76 cases received radiation, another 20 cases received M protocol chemotherapy (cyclophosphamide, etoposide, gentamycin, vincristine and adriamycin) instead of radiation. The 3 year EFS rate for these two groups were (84.7±4.3)% and (84.7±8.1)%(χ 2=0.015, P=0.902). There were 22 renal clear cell sarcoma and 5 malignant rhabdoid tumor, 3 year EFS rate of them was (94.4±5.4)% and (20.0±17.9)%. Univariate analysis was performed for age, gender, pathological type, stage, whether rupture occurred during operation, whether complete remission (CR) occurred at the end of treatment and radiotherapy. Pathological types (χ 2=44.329, P<0.01) and failure to achieve CR at the end of the treatment (χ 2=49.459, P<0.01) were independent factor for predicting survival. Conclusion:Compared with CCCG-WT-2009, treatment of renal tumors in CCCG-WT-2015 study yielded good survival outcome, which can be further applied.

Objective To investigate the correlation between serum miR-320b and carotid atherosclerosis in patients with acute ischemic stroke.Methods From January 2017 to December 2017,patients with acute ischemic stroke visited the Department of Neurology,the Affiliated Hospital of Yangzhou University were enrolled.According to the findings of carotid artery ultrasonography,they were divided into plaque group and plaque-free group.The baseline clinical data such as demographic data,vascular risk factors,and blood biochemical indicators were collected.Reverse transcription quantitative polymerase chain reaction was used to detect the expression level of serum miR-320b.Multivariatelogistic regression analysis was used to determine the independent risk factors for carotid atherosclerosis.Results A total of 135 patients with acute ischemic stroke were enrolled in this study,including 58 females and 77 males,aged 58.4 ± 10.6 years.There were 85 patients in the plaque group and 50 in the plaque-free group.The total cholesterol (t =5.523,P =0.023) and low-density lipoprotein cholesterol (t =4.415,P =0.044) in the plaque group were significantly higher than those in the plaque-free group,while high-density lipoprotein cholesterol (t =5.849,P=0.017) and serum miR-320b (t =4.331,P=0.039) were significantly lower than those in the plaque-free group.Multivariate logistic regression analysis showed that referring to the highest quartile group,the low serum miR-320b level might be an independent risk factor for carotid atherosclerosis (the first quartile group:odds ratio 2.701,95％ confidence interval 1.154-6.321,P =0.022;the second quartile group:odds ratio 2.521,95％ confidence interval 1.249-5.091,P =0.010;and the third quartile group:odds ratio 1.849,95％ confidence interval 1.041-3.283,P=0.036).Conclusion The low serum miR-320b level might be an independent risk factor for carotid atherosclerosis in patients with acute ischemic stroke.

The clinical application of doxorubicin (DOX) in cancer chemotherapy is limited by its life-threatening cardiotoxic effects. Chrysophanol (CHR), an anthraquinone compound isolated from the rhizome of L., is considered to play a broad role in a variety of biological processes. However, the effects of CHR׳s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide (3AB) and ABT888. Ectopic expression of PARP1 effectively blocked this CHR׳s cardioprotection against DOX-induced cardiomyocyte injury in H9C2 cells. Furthermore, pre-administration with both CHR and 3AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague-Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy.

Objective: To study the clinical efficacy of Sini-Moxibustion in the treatment of cancer-induced fatigue in patients with yang- deficiency gastrointestinal cancer. Methods: A total of 120 patients with gastrointestinal cancer treated in our department from January 2017 to January 2018 were randomly divided into 2 groups: the fire moxibustion group and the conventional group. The conventional group and the fire therapy group were treated with basic treatments such as anti-cancer and nutritional support. The conventional group added Sini-Moxibustion to the basic treatment, and the fire therapy group added"Sini-Moxibustion"therapy for a period of 1 month. Tthe indicators of the 2 groups of patients with Piper fatigue scale and grade, quality of life, symptoms of yang deficiency symptoms, clinical efficacy and blood tests of patients with chemotherapy were evaluated. Results: After the treatment, the degrees of fatigue in the fire moxibustion group was lower than that in the conventional group with statistically significant difference ( χ2 =4.24, P =0.037 ＜ 0.05). The scores of improvement in the quality of life scale and five subscales in the fire moxibustion were higher than those in the conventional group with statistically significant difference (P ＜ 0.01), and the improvement score of the body yang deficiency in the fire moxibustion group was greater than that of the conventional group (P ＜ 0.01). The scores of fatigue, nausea and vomiting, insomnia, anorexia, and diarrhea in the fire moxibustion group were higher than those in the conventional group with statistically significant difference (P ＜ 0.05 or P ＜ 0.01). After treatment, the total effective rate was 76.67％ in the fire moxibustion treatment group, which was higher than the conventional group 91.53％ with statistically significant difference ( χ2 =5.64, P =0.012 ＜ 0.01). Hemoglobin improvement value of 3.92 ± 1.18 in the fire moxibustion group was higher than that of the conventional group 1.02 ± 0.52 with statistically significant difference (t =7.212, P =0.003 ＜ 0.01). Conclusion: Sini-moxibustion can improve the CRF of patients with yangdeficiency gastrointestinal cancer, reduce the symptoms of yang deficiency, improve the quality of life, and increase the hemoglobin content in patients with chemotherapy.