Objective To investigate the protective effect and mechanism of J147 on the injury of human neuroblastoma cells(SH-SY5Y)induced by high glucose(HG).Methods We established HG-induced SH-SY5Y cell injury model.Then SH-SY5Y cells were divided into blank control(Con)group HG group,HG+J147 0.5 μmol/L(HG+J147 0.5)group,HG+J147 1 μmol/L(HG+J147 1)group,HG+J147 2 μmol/L(HG+J147 2)group,HG+PI3K/AKT inhibitor LY294002(LY)10 μmol/L(HG+LY)group,HG+ERK1/2 inhibitor U0126(U0)5 μmol/L(HG+U0)group,HG+J147 2 μmol/L+LY 10 μmol/L(HG+J147 2+LY)group,HG+J147 2 μmol/L+U0 5 μmol/L(HG+J147 2+U0)group.Cell viability was detected by MTS cell proliferation and toxicity detection kit;LDH activity was tested by lactate dehydrogenase kit;morphological changes of SH-SY5Y cells were evaluated by microscope;cell apoptosis was detected by flow cytometry;and apoptosis-related proteins(Bcl-2,Bax)and signaling pathway-related proteins(p-AKT,AKT,p-ERK1/2,ERK1/2,p-CREB,CREB,BDNF)were detected by Western blot.Results Compared with Con group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions decreased(P<0.01),while LDH activity and apoptosis rate increased in HG group(P<0.01).Compared with HG group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions increased(P<0.01),while LDH activity and apoptosis rate decreased in HG+J147 2 group(P<0.01).Compared with HG+J147 2 group,the cell viability,Bcl-2/Bax ratio,p-AKT/AKT and BDNF protein expression decreased(P<0.05 or P<0.01),while LDH activity and apoptosis rate increased(P<0.05 or P<0.01),the expression of p-ERK/ERK protein in HG+J147 2+LY group decreased(P<0.05),and the expression of p-CREB/CREB protein in HG+J147 2+U0 group decreased in HG+J147 2+LY and HG+J147 2+U0 groups(P<0.05).Conclusions J147 can alleviate HG-induced SH-SY5Y cell damage,and the mechanism may be related to the activation of PI3K/AKT and ERK1/2 signaling and the reduction of apoptosis.

Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with B-cell lymphoma may experience immunodeficiency due to the disease itself and its treatment, making them a high-risk group for susceptibility and severe outcomes of COVID-19. Therefore, it is crucial to analyze the baseline characteristics of B-cell non-Hodgkin lymphoma patients diagnosed with COVID-19, investigate common risk factors, evaluate the efficacy of vaccination and assess the immune deficiencies induced by immunotherapy, particularly CD20 monoclonal antibodies. For B-cell NHL patients with COVID-19, an individualized assessment of risk factors is necessary. This review discussed the immune response of lymphoma patients to COVID-19, summarized the characteristics of lymphoma patients following COVID-19, analyzed the vaccine effectiveness in this population, and explored the impact of COVID-19 on the onset and anti-tumor treatment of B-cell non-Hodgkin lymphoma, along with associated risk factors, aiming to provide recommendations for formulating treatment strategies and clinical management.

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.

Hepatitis B virus (HBV) infection is a major global public health issue. Clinical cure (also known as functional cure) of chronic hepatitis B (CHB) is the ideal therapeutic goal recommended by the latest guidelines for the prevention and treatment of CHB in China and globally. Optimized treatment regimens with direct-acting antiviral agents ［e.g., nucleos(t)ide analogues］ or immunomodulators (e.g., pegylated interferon-α) sequentially or in combination tend to have low cure rates. Rapid development has been achieved in the research and development of drugs for the treatment of CHB. This article reviews the clinical study of new antiviral drugs for CHB, including the selection of subjects, study design, dosage, dose escalation, adverse events, and efficacy evaluation. It is necessary to introduce the knowledge of quantitative pharmacology to analyze the association of drug exposure in body with efficacy and adverse reactions, and exploratory indicators should be incorporated for comprehensive analysis. This review provides related experience and new ideas for the clinical research and development of new anti-HBV drugs.

Objective:To explore the effects of hnRNP E1 on the expression of early genes E2, E6 of HPV16 and the biological function in cervical cancer SiHa cell lines.Methods:The cell experiments in vitro were carried out in cervical cancer cell lines SiHa. The expression levels of E2, E6 mRNA and protein of HPV16 were detected by Real-time PCR and Western blot, respectively, before and after up-regulating hnRNP E1. Meanwhile, the cell proliferation, cycle and apoptosis were evaluated by CCK-8 and flow cytometry. Data analyses were performed using SPSS 22.0 and Graphpad Prism 7.0 software. Results:Compared with the blank and the blank plasmid group, the cells activity and proliferation decreased at 24, 48 and 72 h after up-regulating hnRNP E1 ( P<0.05), while the percentage of cells in G0/G1 phase increased and the percentage in S and G2/M phase and proliferation index decreased ( P<0.05). Moreover, the late apoptotic rate and the total apoptotic rate increased ( P<0.05). The expression levels of E6 mRNA and protein of HPV16 in hnRNP E1 up-regulated group were significantly lower than that in both blank group and blank plasmid group, the differences were significant ( P<0.05), showing the tendency of cells proliferation index decrease and total apoptotic rate increase with decreased HPV16 E6 expression. There were no significant differences in the expression of E2 mRNA of HPV16 among the three groups ( P=0.427), and no E2 protein of HPV16 was detected. Conclusions:hnRNP E1 could inhibit the transcription and translation of E6 oncogene of HPV16 and further inhibit the proliferation and promote apoptosis of cervical cancer cells, suggesting that hnRNP E1 might be a potential target marker to prevent cervical lesions. But no association between hnRNP E1 and HPV16 E2 was found in SiHa cells.

Objective: The aim of this study is to evaluate the diagnostic value of turbo spin-echo（TSE） diffusion weighted imaging（DWI） in temporal bone cholesteatoma. Method: A prospective evaluated of 76 patients with suspected sacral cholesteatoma was performed using a Philips Ingenia 3.0T superconducting magnetic resonance scanner and a 32-channel head coil with turbo spin-echo diffusion weighted imaging（TSE-DWI） sequence and conventional magnetic resonance scan, and underwent surgery within the next two weeks. The pathological result is the gold standard, and the imaging diagnosis and surgery are performed. The intraoperative observation and pathological results were compared. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of TSE-DWI sequence in the diagnosis of temporal bone cholesteatoma were calculated. Result: Of the 76 patients with suspected temporal bone cholesteatoma, TSE-DWI scan was performed, 44 cases were diagnosed as cholesteatoma and 32 cases were non-cholesteatoma. Based on the pathology results, 46 cases were diagnosed as cholesteatoma, 30 cases were non-cholesteatoma. The accuracy of TSW-DWI sequence in the diagnosis of cholesteatoma was 89.47%, 3 cases were false negative and 5 cases was false positive. The sensitivity, specificity, positive predictive value and negative predictive value of TSE-DWI in the diagnosis of temporal bone cholesteatoma were 89.13%, 90.00%, 93.18%, and 84.38%, respectively. Conclusion The TSE-DWI sequence has high signal-to-noise ratio and can improve the diagnostic accuracy and specificity. TSE-DWI sequence is of great value in clinical diagnosis and treatment.