Objective To investigate radiation-induced alternations of phospholipids in epithelial cells,and to provide experimental evidence for understanding the mechanism of radiation-induced intestinal injury.Methods The intestinal epithelial cells(IEC-6)in rats were divided into three groups:normal control group,8 Gy X-ray irradiation group and 12 Gy X-ray irradiation group.Phospholipids were extracted at 6 h or 24 h after radiation and then measured by high-performance liquid chromatography and mass spectrometry(HPLC-MS).Results At 6 h after radiation,the phospholipids in 8 Gy irradiation group didn't vary significantly,while those in 12 Gy irradiation group changed.The PG,PI and Lyso PC were significantly up-regulated(F=5.37,9.60,9.88,P＜0.05).However,at 24 h after radiation,many PE and PG species in both irradiation groups declined(F=5.15-99.77,P＜0.05)and SM species increased in 12 Gy irradiation group(F=4.35-7.92,P＜0.05).Conclusions The ionizing radiation could disorder phospholipid metabolism in IEC-6 cells with a dose-dependent manner.

T A R D N A-binding dom ain protein 43 (T D P-43) is a highly conserved and w idely expressed nuclear protein. N ow adays, the expression of T D P-43 can be found in m ost neurodegenerative diseases such as A lzheim er's disease, w hich m akes it becom e a neurodegenerative disease associated m arker pro-tein. From the current research status at hom eland and abroad, and around the relationship betw een the expression of T D P-43 and brain injury, this article em phatically probes into the specific expression and function of T D P-43 in acute and chronic brain injury based on the know ledge of its biological charac-teristics, w hich aim s to explore the feasibility for determ ining the cause of death and the injury and dis-ability situations by T D P-43 in forensic pathology.

Biomarkers ; Breast Neoplasms ; Breast ; Drug Therapy ; Humans ; Neoadjuvant Therapy ; Neoplasm, Residual ; Pathology ; Prognosis ; United States Food and Drug Administration

Since the impact of food on innovative drugs exposure will increase the risk of evaluation failures for safety and effectiveness, food effect study is routinely completed before multiple ascending dose (MAD) trials for innovative drugs. The prediction performance of physiologically-based pharmacokinetic absorption model (absorption PBPK model) in the application of food effect prediction has improved, we proposed a new strategy to explore food effect based on the absorption PBPK model. Based on the accurate prediction by absorption PBPK model, the food effect studies for qualified innovative drugs would be nested in MAD clinical trials to intend replacing the early independent food effect study. That would be promising to reduce costs and time for drug development, and also to provide the template for early food effect study in China.

Purpose: Combining targeted agents with adjuvant chemotherapy prolongs survival in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, but also increases the risk of adverse effects. The updated results of 3 randomized controlled trials (RCTs) were reported in 2019. Given the lack of adequate head-to-head pairwise assessment for anti-HER2 agents, network meta-analysis facilitates obtaining more precise inference for evidence-based therapy. Methods: RCTs comparing at least 2 anti-HER2 regimens in an adjuvant setting for HER2-positive early-stage breast cancer (EBC) were included. Hazard ratios for overall survival (OS) and disease free survival (DFS), with respective 95% confidence intervals were pooled for assessment of efficacy. A Bayesian statistical model was used, and odds ratios (ORs) for adverse events (AEs) were used to pool effect sizes. Results: We demonstrated that 1-year trastuzumab plus chemotherapy had increased efficacy compared to shorter or longer treatment duration. The OR of cardiac events gradually increased from 6 months to 1 and 2-year trastuzumab arms, relative to chemotherapy only.Compared to trastuzumab plus chemotherapy, dual HER2-targeting therapies increased DFS, especially for hormone receptor negative patients. Dual anti-HER2 blockade regimens revealed an increased probability of gastrointestinal reactions. As a second agent, pertuzumab showed significantly higher DFS and OS. Conclusion We conclude that 1-year adjuvant trastuzumab should remain as the standard treatment for HER2-positive EBC patients, as it has greater efficacy and a manageable proportion of AEs. Clinical efficacy can be increased for hormone receptor-negative tumors by including a second HER2-targeted agent to the treatment regimen. For hormone receptorpositive cases with basal disease, it is acceptable to reduce the risk of cardiotoxicity by shortening the duration of trastuzumab.

Objective:To construct a novel respiratory syncytial virus (RSV) vaccine based on a recombinant influenza virus vector and evaluate its immune protective effects in mice.Methods:A recombinant H1N1 influenza A virus (IAV) expressing the extracellular domain (Gecto) of RSV A2 G protein was constructed and rescued, named as PR8NAGecto/WSN. After in vitro verification of the Gecto expression and PR8NAGecto/WSN growth kinetics, a single dose of PR8NAGecto/WSN was used to immunize BALB/c mice through intranasal administration to evaluate the efficacy of PR8NAGecto/WSN by assessing humoral (IgG, neutralizing antibody), mucosal (IgA) and cellular immunity (IFN-γ ELISPOT). Four weeks after immunization, the mice were challenged with RSV A2 or RSV B9320 to evaluate the protective effects of PR8NAGecto/WSN by analyzing mouse body weight changes, lung tissue virus titers and pathological changes. Results:A single-dose intranasal immunization with PR8NAGecto/WSN induced robust humoral, mucosal and cellular immunity in mice. Moreover, the mice in the immunized group had lower lung virus loads and mild lung pathological damages following the challenge with RSV A or RSV B subtype as compared with the control group.Conclusions:A single-dose intranasal immunization with PR8NAGecto/WSN induces robust immunity and provide protection against RSV A and B challenges in mice. This study provides new ideas and reference for the development of novel mucosal vaccines against RSV.

Objective: To prepare peptide minotope-based recombinant diagnostic antigen of Epstein-Barr virus (EBV) infection and evaluate its antigenicity preliminarily. Methods: With Trx at the N-terminal and His tag at the C-terminal, the peptide minotope of EBV (GP125, F1, A2, A3C2) was expressed in Escherichia coli and purified by affinity and anion exchange chromatography (designated 'H58’); based on antigenicity of H58 identified by Western blotting (WB), we constructed and evaluated a novel early diagnostic ELISA for EBV infection. Results: The soluble H58 protein with high concentration (2.8 mg/ml) and purity (99.01) was obtained; WB analysis found that there was an obvious band (28 ×10³) on the NC membrane, using H58 anti-Trx monoclonal antibody or acute-phase sera of EBV infection as the first antibody. With the novel ELISA, 50 positive sera of EBV infection and 50 negative sera were detected, displaying that the grouping of OD value of positive serum (95%CI: 1.233-1.489) and negative serum (95%CI: 0.113-0.159) was different (P<0.05) with the sensitivity 98.0%, specificity 96.0% and kappa value 0.940. Conclusions By E. coli expression and affinity and ion exchange chromatography purification, the peptide minotope-based recombinant diagnostic antigen of EBV infection was obtained with excellent antigenicity, which could be applied for serological detection of EBV infection.

Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.