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With the enormous resources having been invested in oncology drugs development in China in recent years, the Center for Drug Evaluation (CDE) of National Medical Products Administration has been issuing a number of technical guidelines to further standardize the requirements on implementation and registration of domestic oncology clinical trials. As data is the cornerstone of clinical trials, data integrity and quality will directly decide the outcome of clinical studies. Given the specific characteristics of oncology therapeutic clinical trials, and combined with the clinical data standards established by the Clinical Data Interchange Standards Consortium (CDISC) and the issued industrial guidelines, this article introduces the general considerations of clinical data management for oncology clinical trials, with the aim of emphasizing normative data collection and timely data monitoring to ensure the data quality and reliability of results of the study. This article discusses the impact of complex study design on CRF, design CRF according to CDASH, develop DVP scientifically, rolling submissions and data cut-off.
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Objective:To investigate the correlation between neutrophil/lymphocyte ratio (NLR) combined with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and severity of coronary lesions in patients with acute coronary syndrome (ACS).Methods:Patients who were diagnosed with ACS due to chest pain and received emergency coronary angiography in the First Affiliated Hospital of University of Science and Technology of China and the Affiliated Hospital of Anhui Medical University from January 2017 to June 2020 were enrolled in the final analysis. The data of gender, age, body mass index (BMI), past history, emergency blood routine indicators [neutrophil (NEU), lymphocyte (LYM), monocyte (MON), eosinophil (EOS), basophil (BAS), red blood cell (RBC), mean corpuscular volume (MCV), blood red cell distribution width (RDW), mean platelet volume (MPV), platelet volume distribution width (PDW)], blood lipid index [triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, very low-density lipoprotein cholesterol (VLDL-C)], and coronary angiography were collected. The results of coronary angiography were evaluated by the Gensini score. According to the Gensini score, the patients were divided into the control group (Gensini score = 0, 55 cases) and the study group (Gensini score > 0, 889 cases), and then the patients in the study group were divided into the low-Gensini-score group (Gensini score < 66, 419 cases) and the high-Gensini-score group (Gensini score ≥ 66, 470 cases). The differences in the general baseline data of the four groups were compared, and the correlation between the statistically significant data and the Gensini score was linearly analyzed, and then the combined diagnostic factors (NLR combined with LDL-C/HDL-C ratio) were obtained by Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of NLR combined with LDL-C/HDL-C ratio in predicting the severity of coronary artery lesions in patients with ACS. Finally, multivariate linear regression analysis was used to establish the predictive model between NLR combined with LDL-C/HDL-C ratio and Gensini score.Results:A total of 944 patients were finally included. The differences in gender, age, BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, EOS, RDW, TC, HDL-C, LDL-C, NLR, LDL-C/HDL-C ratio between the control group and the study group were statistically significant. The differences in BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, EOS, TG, TC, HDL-C, LDL-C, NLR and LDL-C/HDL-C ratio between the low-Gensini-score group and the high-Gensini-score group were statistically significant. Linear regression analysis showed that compared with other indicators, the correlation between NLR, LDL-C/HDL-C ratio and Gensini score was stronger in the study group ( r values were 0.634 and 0.663, respectively, both P < 0.05). Binary Logistic regression analysis of the indicators related to Gensini score showed that NEU, LYM, HDL-C and LDL-C were independent risk factors for coronary stenosis in patients with ACS [odds ratio ( OR) were 0.189, 10.309, 13.993, 0.251, 95% confidence intervals (95% CI) were 0.114-0.313, 4.679-22.714, 3.402-57.559, 0.121-0.519, respectively, all P < 0.05]. ROC curve analysis showed that NLR combined with LDL-C/HDL-C ratio had higher predictive value in predicting the severity of coronary lesions in ACS patients [area under the ROC curve (AUC) was 0.952, 95% CI was 0.93-0.969], when the cutoff value was -3.152, the sensitivity was 98.20%, and the specificity was 81.60%. According to the results of multivariate linear regression analysis, the prediction model between NLR, LDL-C/HDL-C ratio and Gensini score was established, and the formula was Gensini score = -7.772+15.675×LDL-C/HDL-C ratio+8.288×NLR ( R2 = 0.862). Conclusion:There is a significant correlation between emergency NLR combined with LDL-C/HDL-C ratio and Gensini score in patients with ACS at admission, which has a certain predictive value for the severity of coronary artery stenosis in patients with ACS, and can be used as a predictor for evaluating the severity of coronary artery disease.
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Objective To investigate the effect of hypobaric hypoxia on the respiratory function of C5 spinal cord injury rats by simulating the environment of low pressure and low oxygen in air transport. Methods 20 male SD rats were randomly divided into 3 groups: sham operation group (n=4), spinal cord injury group (n=8) and spinal cord injury + low pressure group (n=8). Spinal cord injury model was made by compression method. These rats in the three groups were treated with carotid artery catheterization, and were fed for 24 hours. Spinal cord injury + low pressure group was put into 2500 m low pressure environment for 4 hours. Arterial blood gas, blood routine test, HE staining of the spinal cord and lung tissue were detected to evaluate respiratory function, and BBB score was used to evaluate motor function of rats. Results There was no significant difference between the three groups in pH, oxygen partial pressure, carbon dioxide partial pressure, oxygen saturation, glucose, lactate, alkali surplus, buffer alkali and other indicators (P>0.05). The percentage of reticulocyte in spinal cord injury group was lower than that in sham operation group (2.05%±0.69% vs. 2.88%±0.20%, P=0.034), there was no significant difference between spinal cord injury + low pressure group and other two groups (2.37%±0.59% vs. 2.88%±0.20%, P=0.178; 2.37%±0.59% vs. 2.05%±0.69%, P=0.282). There was no significant difference among the three groups in the leukocyte counts and percentage of neutrophils, lymphocytes, monocytes, erythrocytes, hemoglobin and hematocrit (P>0.05). HE staining showed that there was no obvious bleeding and exudative changes in spinal cord in sham operation group, and the tissue structure was intact. The histological integrity of spinal cord injury group and spinal cord injury + low pressure group was significantly different from that of sham operation group, but there was no significant difference between the two groups. There was no significant difference in bleeding, exudation and edema between the three groups, and the alveolar structure was intact. BBB score showed no significant difference between spinal cord injury group and spinal cord injury + low pressure group (P=0.440). Conclusion The respiratory and motor function of C5 spinal cord injury rats would not be significantly affected by 4 hours of low pressure and hypoxia.
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Objective· Formalin is a classic and most widely used algogenic substance,but its itchy effect is not clear.The present study aims to explore the hypothesis that formalin may induce itch as well as pain.Methods· Flinching,as well as licking and forelimb wiping of the site of injection were counted as pain responses,whereas biting and hind paw scratching of the cheek were counted as itchy responses.To discriminate formalin-induced sensations in rats,the irritant (saline as control) was injected,and then pain and itchy responses were recorded.Results · Intraplantar injection of formalin elicited biphasic behavior responses characterized as flinching,as well as biting or licking of the hind paw without significant gender differences.Following intradermal administration of formalin to the cheek,rats exhibited episodic forelimb wiping of the cheek,representative of pain.No gender difference was noticed for this type of behavior.In addition,episodes of hind paw scratches of the cheek,representative of pruritoceptive responses,also occurred.Interestingly,hind paw scratches appeared to be more pronounced in male than in female rats.Conclusion · Intradermal administration of formalin elicits pruritoceptive as well as nociceptive responses in rats.
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Numerous studies have demonstrated that estrogens may exert multifaceted effects on the cardiovascular system via activating the classical nuclear receptors ERα or ERβ and the novel G protein coupled estrogen receptor (Gper). However, some studies have reported inconsistent cardiovascular phenotypes in Gper-deficient mice. The current study was aimed to reveal the effects of genetic deletion of Gper on the arterial blood pressure (ABP) and heart rate in rats. Gper-deficient Sprague-Dawley rats were generated by utilizing the CRISPR-Cas9 gene-editing technique. ABP of 10-week old male (n = 6) and 12-week old female (n = 6) Gper-deficient rats and age-matched wild type (WT) rats (6 females and 6 males) were measured under awake and restrained conditions through the non-invasive tail-cuff method daily for 8 (females) or 9 days (males). In the male WT rats, ABP and heart rate were slightly higher in day 1 to 4 than those in day 5 to 9, indicative of stress-related sympathoexcitation in the first few days and gradual adaptation to the restrained stress in later days. Gper-deficient rats had significantly higher ABP initially (male: day 1 to day 5; female: day 1 to day 3) and similar ABP in later days of measurement compared with the WT rats. The heart rate of male Gper-deficient rats was consistently higher than that of the male WT rats from day 1 to day 8. Both male and female Gper-deficient rats appeared to show slower body weight gain than the WT counterparts during the study period. Under anesthesia, ABP of Gper-deficient rats was not significantly different from their WT counterparts. These results indicate that Gper-deficient rats may be more sensitive to stress-induced sympathoexcitation and highlight the importance of Gper in the regulation of the cardiovascular function in stressful conditions.
