Objective To investigate the diagnostic value of serum FER, AFP and AFP-L3 alone or in combination for diagnosis of primary hepatic carcinoma( PHC).Methods This was a case-control study.
Serum FER, AFP and AFP-L3 were determined in 212 patients with PHC ( StageⅠ45 cases, StageⅡ78 cases, StageⅢ81 cases, StageⅣ8 cases) , 127 patients with cirrhosis, 101 patients with chronic hepatitis and 98 controls in the Beijing Youan Hospital affiliated to Capital Medical University from January 2014 to December 2014.Levels of FER, AFP and AFP-L3 were measured by chemiluminescence, while serum samples were pre-treatment with affinity adsorption before AFP-L3 detection.FER, AFP and AFP-L3 levels were analyzed using the nonparametric Wilcoxon test among all groups.Diagnostic performance were analyzed among the groups with the three biomarkers independently and combined.Logistic regression, plotted ROC curve and calculated the area under ROC curve ( AUC) were applied to assess the diagnostic value of each index.Results Serum concentration of FER in PHC, cirrhosis, chronic hepatitis groups and healthy controls were 308.45 ( 148.98 -662.80 ) , 151.70 ( 51.44 -507.40 ) , 298.20 ( 157.30 -701.80 ) , 113.50( 54.98-221.38) μg/L, respectively.The concentration of AFP were 48.50(5.25 -748.40), 3.91(1.80-17.53), 4.76 (2.29-30.56), 2.57 (0.93-3.68) μg/L in each group.The serum levels of AFP-L3 in each group were 4.75(0.61-127.95), 0.61 (0.61-2.50), 0.61 (0.61-2.85), 0.61 (0.61-0.61) μg/L.The concentration of FER, AFP and AFP-L3 differs statistically in PHC, cirrhosis, chronic hepatitis group and healthy controls (χ2 =67.66,146.31,119.02,P<0.001).The content of serum FER, AFP and AFP-L3 increased gradually as the stage level aggravating ( StageⅠ-Ⅳ) , there was significant differences among groups (χ2 =21.63,22.68,21.98, P<0.001) .When using one serum marker, FER had the highest sensitivity (75.00%) , while AFP-L3 had the highest specificity (82.52%). While using two serum markers, FER/AFP had the highest sensitivity (89.15%) , FER+AFP-L3 and AFP+AFP-L3 had a higher specificity (86.20%).The combined detection of FER/AFP/AFP-L3 improved the sensitivity of the test to 89.15%, while FER+AFP+AFP-L3 had a specificity of 86.50%.The AUC of combination of FER, AFP and AFP-L3 was 0.803 ±0.019 (95% CI:0.765-0.841), which was higher than the AUC of either FER(0.748 ±0.022,95% CI:0.705-0.790, Z=4.67,P<0.001) and AFP-L3 (0.726 ±0.024,95% CI: 0.679 -0.772, Z=3.64,P<0.001).However, there was no significant difference in AUC between AFP alone ( 0.776 ±0.021, 95% CI: 0.735 -0.818 ) and the combined detection ( Z=1.34, P=0.18 ) .Conclusions FER was a potential marker for PHC diagnosis.The combination of FER, AFP and AFP-L3 has higher value of clinical applications than one of them independently.

ObjectiveTo investigate the tolerance, pharmacokinetics, and antiviral activity of coblopasvir hydrochloride capsules in patients with hepatitis C. MethodsA total of 36 patients with hepatitis C who were admitted to The First Hospital of Jilin University from November 2016 to January 2017 were enrolled as subjects, and four dose groups (30 mg, 60 mg, 90 mg, and 120 mg) and one placebo group were established. The subjects were administered once daily for 3 consecutive days; tolerance was evaluated on D2 and D6, and follow-up was performed on D8 and D10. The subjects were enrolled based on single dose escalation, and a multiple-dose study was conducted under the premise of good tolerance to single dose. Liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of coblopasvir hydrochloride in human body, and WinNonlin 6.4 software was used to calculate main pharmacokinetic parameters. HCV RNA load was used to evaluate antiviral activity at different time points; a one-way analysis of variance was used for comparison between multiple groups, and the LSD t-test was used for further comparison between two groups. ResultsAfter coblopasvir hydrochloride capsules were administered orally once a day at a dose of 30-120 mg, the plasma concentration and exposure of coblopasvir hydrochloride increased with the increase in dose. There were no significant differences in plasma concentration and exposure between multiple-dose administration and single-dose administration in a fasting state, without accumulation in human body. After the oral administration of coblopasvir hydrochloride capsules once a day, the subjects with HCV genotype 1b had a reduction in HCV RNA load since baseline, with the lowest level at 120 hours, and there was a significant difference in antiviral activity between different dose groups (F=14.621, P＜0.000 1), among which the 60 mg group had a significantly greater reduction than the 30 mg group (P=0.025), while there was no significant difference between the 60 mg group and the 90/120 mg group (P＞0.05). There was no significant difference in HCV RNA load between different groups of patients with HCV genotype 2a (P＞0.05). Of all 36 subjects, 20 reported 34 cases of treatment-emergent adverse events, among which 19 cases were associated with coblopasvir hydrochloride, and no significant adverse events or serious adverse events were observed. ConclusionOral administration of coblopasvir hydrochloride capsules in a fasting state at a dose of 30-120 mg/d (for 3 consecutive days) has good safety and antiviral activity. Therefore, it has good application prospect in the treatment of HCV infection and provides a basis for dose selection in phrase 2 study.

Objective:To construct a close-loop path management model for aspiration risk screening of patients in Department of Neurosurgery, and verify its application effect in the nursing of inpatients in department of neurosurgery.Methods:Through literature retrieval and expert consultation, the close-loop path management model of aspiration risk screening was constructed. The convenient sampling method was adopted to select inpatients in the Neurosurgery Department of a ClassⅢ Grade A hospital in Jiangmen of Guangdong Province from January to December 2019. The patients admitted from January to June 2019 were set as the control group and received routine aspiration assessment and management while the patients admitted from July to December 2019 were set as the observation group and received close-loop management of aspiration risk screening. The incidences of aspiration and aspiration pneumonia were compared between the two groups.Results:In the control group, there were 506 patients, of whom 92 (18.18%) had aspiration. In the observation group, there were 543 patients, of whom 74 (13.63%) had aspiration. There was a statistically significant difference in the incidence of aspiration between the two groups (χ 2=4.078, P=0.043) . The incidence of aspiration pneumonia was 8.10% (41/506) in the control group and 5.52% (30/543) in the observation group. There was no statistically significant difference between the two groups (χ 2=2.758, P=0.097) . Conclusions:The close-loop management of aspiration risk screening standardizes the process of aspiration risk screening, guarantees the implementation of dynamic assessment and effectively reduces the incidence of aspiration, which can provide a reference for improving the management level of prevention and treatment of aspiration.

Objective:To investigate the clinical value of peripheral blood T lymphocytes in the diagnosis and prognosis of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation.Methods:The clinical and laboratory data of 50 HCC patients, who received liver transplantation and were followed up in the Liver transplantation Center of Beijing Youan Hospital from January 2014 to December 2016, were retrospectively analyzed. The differences on clinical laboratory indicators and five-year survival were compared between HCC recurrence group ( n=29) and non-recurrence group ( n=21). Spearman correlate analysis was used to analyze the correlation between clinical laboratory indicators and HCC recurrence after liver transplantation. Receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of CD4+T lymphocytes in HCC recurrence after liver transplantation. Kaplan-Meier survival curve was used to compare the survival time of patients with different CD4+T lymphocytes levels post liver transplantation. Results:Compared to non-recurrence group, the level of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, albumin, lymphocytes, alpha-fetoprotein, protein induced by vitamin K deficiency or antagonist-Ⅱ, CD3+, CD4+and CD8+T lymphocytes were significantly different (all P<0.05). The median recurrence time after liver transplantation was 13.0 (6.0, 24.0) months, and the mortality rate was 100%. The 5-year mortality rate was 0 in the non-recurrence group. During 5-year follow-up, the median survival time of patients in the HCC recurrence group was 18.0 (9.0, 36.0) months, which was significantly lower than that of non-recurrence group [60.0 (60.0, 60.0) months, ( P<0.05)]. Compared with non-recurrence group, the CD3+, CD4+, and CD8+T lymphocytes were significantly lower in the recurrence group (all P<0.05). Spearman correlate analysis showed that HCC recurrence after liver transplantation was negatively correlated with the CD3+, CD8+and CD4+T lymphocytes ( r=-0.43, -0.38, -0.44, all P<0.05). ROC analysis showed that CD4+T lymphocytes at cutoff of≤265.50 cells/μl was valuable for the diagnosis of HCC recurrence after liver transplantation (specificity 100%, sensitivity 48.30%). Survival curve analysis showed that the survival time was significantly lower in the CD4≤265.50 cells/μl group [15.0 (10.0, 36.8) months] than that in the CD4>265.50 cells/μl group [53.0 (19.5, 60.0) months] ( P<0.05). Conclusion:There is a significant negative correlation between CD4+T lymphocytes and HCC recurrence after liver transplantation. CD4+T lymphocytes at cutoff value of≤265.50 cells/μl is valuable for the clinical diagnosis and prognosis evaluation of HCC recurrence after liver transplantation.

Teaching in experiments of biology is important for the cultivation of life science talents. In view of the rapid development of life science and the increasing demand for research-oriented talent training, teaching in experiments of biology should set up a variety of learning outcomes: to train experimental skill, to cultivate students' experimental design and operation abilities, and to improve students' scientific thinking and innovative consciousness. We have carried out an educational reform on experimental genetic engineering blended course. In this paper, we introduced our methods of organizing online materials, the curriculum design of the blended course, the implementation details, and a preliminary analysis of teaching effects. We found that experimental genetic engineering blended course could support students' active learning and a learning-centered teaching model. Moreover, it could facilitate students' achievement of improving experimental skills, cultivating a rigorous scientific attitude, professional research quality and academic innovation ability.
Biological Science Disciplines ; Curriculum ; Genetic Engineering ; Humans ; Students

Objective: To analyze the serological characteristics of anti-mitochondrial antibody M2 subtype (AMA-M2) in patients with drug-induced liver injury (DILI) and primary biliary cholangitis (PBC), in order to provide reference for clinical differential diagnosis. Methods: Laboratory data of 2802 DILI cases who visited the hospital between January 2011 and December 2017 were retrospectively collected. AMA-M2 positive patients were analyzed with respect to laboratorical findings, and serum data of 120 patients with primary biliary cholangitis (PBC) at the same period was taken as a control. A chi-square test was used for group comparisons. One-way ANOVA and rank sum tests was used for ALT, AST, ALP, GGT and three groups of immunoglobulin M. Results: Among 2802 DILI patients, AMA-M2 positive rate was 5.1% (144/2 802), 77.1% (111/144) was DILI alone, 22.2% (32/144) was DILI with PBC, and 0.7% (1/144) was DILI with Sjogren's syndrome. An AMA-M2 level in DILI alone group was mostly mild and moderate than the PBC group and the DILI combined with the PBC group. There was significant difference between the two groups (P < 0.05).There was no significant difference in AMA-M2 levels between DILI group combined with PBC group and PBC group (P > 0.05). ALT and AST levels of DILI alone group and DILI combined with PBC were (585.92 ± 653.04) U/L, (501.45 ± 512.67) U/L and (373.47 ± 502.60) U/L, (335.97 ± 513.96) U/L, respectively, which were significantly higher than PBC group [(106.33 + 134.08) U/L, (112.59 + 152.20) U/L]. There were statistically significant differences between the two groups (P < 0.05).The ALP level of DILI alone group was (152.58 + 81.46) U/L, which was lower than PBC group (237.86 + 215.09). The difference was statistically significant (P < 0.05). The level of immunoglobulin M in the DILI alone group was (1.76 ± 1.16) g/L, which was lower than PBC group (4.74 ± 5.74) g/L and the DILI combined with the PBC group (3.31 ± 1.68) g/L. There was significant difference between the two groups. During follow-up, 2.7% of patients with DILI had cirrhosis, 42.3% had lower AMA-M2 titer, 14.4% had lower AMA-M2 titer, 13.5% had higher AMA-M2 titer and five cases developed PBC. Conclusion AMA-M2 is not only positive in patients with PBC, but also low-to-medium or even high-level AMA-M2 may be detected in DILI patients. For AMA-M2-positive DILI patients, it is necessary to identify whether they are associated with PBC. Secondly, the levels of ALT, AST and ALP should be analyzed, and the patients should be on regular follow up for early and timely detection of drug-induced PBC.