Cargo-laden erythrocyte ghosts target liver mediated by macrophages

Liver-targeted cargo delivery possesses great potential for the treatment of liver disease. It is urgent to find an efficient and biocompatible liver targeted delivery system. This study focused on the liver targeting properties of erythrocyte ghosts and its possible mechanism. Herein, we optimized conditions to fabricate human and mouse erythrocyte ghosts with sufficient room capable of incorporating various model substances. Erythrocyte ghosts are biocompatible cargo carriers because it is derived from autologous red blood cells (RBCs), and the cell size, zeta potential, and biconcave-disk shape of the ghosts were consistent with those of RBCs. An in vivo imaging system and positron emission tomography/computed tomography imaging showed that the ghosts were captured mainly in the liver by intravenous injection of fluorescence or ¹⁸F-fluorodeoxyglucose (FDG)-labelled ghosts into mice. In contrast, the main concentration of naked octreotide was trapped in the lungs while naked ¹⁸F-FDG was trapped in the heart. However, the concentration of cargo-loaded ghosts decreased significantly in the liver in macrophage-depleted mice. Accordingly, in vitro experiments showed that higher phosphatidylserine exposure was observed in the ghosts (38.9 %) compared to normal erythrocytes (0.69 %), and the phagocytic activity of the macrophage RAW 264.7. on the ghosts was significantly higher than that of normal erythrocytes (p < 0.001). Together they indicate that erythrocyte ghosts show liver targeting properties, and possibly owing to macrophage phagocytosis. This promising and effective therapeutic delivery system may provide therapeutic benefits for liver disease.     

嗓音训练联合拳击动作治疗青春期假声的疗效观察

目的观察嗓音训练配合拳击动作治疗青春期假声的临床疗效。方法收集2016年1月—2019年6月在中南大学湘雅医院耳鼻咽喉头颈科就诊的青春期假声患者21例，均为男性患者，年龄16~35岁，病程1~20年。所有患者均表现为青春变声期或变声期后说话时音调偏高或用假声，杂音明显，偶有声嘶及破音，其中19例患者喉镜下表现为声带闭合欠佳。对患者采用嗓音训练联合拳击动作的矫治治疗，根据即时效果反馈，语训1~4次不等，每次1~2 h，以上过程均由专业语训师对患者进行指导及追踪。治疗前后采用动态喉镜及嗓音分析系统记录患者的喉镜下表现及嗓音声学参数，并进行对比分析，评估治疗效果。结果21例青春期假声患者发声基频（F0）较训练前均下降明显，其中18例患者基频恢复至成年男性正常水平，嗓音障碍指数(DSI)较前明显改善，最长发音时间(MPT)较前明显延长，差异具有统计学意义（P＜0.05）； 19例声带闭合不全的青春期假声患者经治疗后声带闭合良好。结论嗓音训练配合拳击动作治疗青春期假声效果显著，有一定的临床应用价值。     

脂肪酸结合蛋白与糖尿病血管病变的研究进展

糖尿病在全球的患病率日益增加,糖尿病血管并发症是目前老龄人群中致死和致残的首要原因。脂肪酸结合蛋白(FABP)是一类脂质伴侣家族,是联结肥胖、糖尿病与血管疾病的关键炎症分子,在糖尿病血管病变中发挥重要作用。本文对FABP家族成员在糖尿病及其血管病变发生发展中的分子机制、作为干预靶点的治疗价值以及成为生物标志物的临床意义进行综述,以期为以FABP为代表的抗糖尿病血管病变的药物研发提供证据与思路。     

Acquisition of Streptococcus pneumoniae in South African children vaccinated with 7-valent pneumococcal conjugate vaccine at 6, 14 and 40 weeks of age

BackgroundSeven-valent pneumococcal conjugate vaccine (PCV7) was introduced into the South African immunization program using 6, 14 and 40 weeks dosing schedule (2 + 1), with no catch-up in older children since April 2009. We investigated pneumococcal colonization acquisition in children who received this schedule and also compared it to historical cohorts of PCV-naïve children (n = 123 in 2007) and children who received a 3 + 1 PCV7 schedule (n = 124 in 2005/06).MethodsTwo hundred and fifty children aged 6–12 weeks were enrolled from December 2009 to April 2010. Participants had nasopharyngeal swabs collected on eight occasions between enrolment and 2-years of age. Standard methods were undertaken for bacterial culture and Streptococcus pneumoniae were serotyped using the Quellung method. Pneumococcal and Staphylococcus aureus colonization in the present study was compared to colonization in two historical longitudinal cohorts.ResultsS. pneumoniae was identified in 1081 (61.4%) of 1761 swabs collected in the current cohort. Pneumococcal colonization peaked at 41-weeks of age (76.8%) and decreased to 62.8% by 2-years of age (p = 0.002); PCV7-serotype colonization decreased during the same period from 28.6% to 15.6% (p = 0.001). Children from the current cohort compared to PCV-naïve children were less likely to be colonized by PCV7-serotypes from 40-weeks to 2-years of age and acquired PCV7-serotypes less frequently. No differences in overall pneumococcal, PCV7-serotype and non-PCV7-serotype colonization or new serotype acquisitions were detected comparing the current cohort to the historical cohort who received the 3 + 1 PCV7 schedule. Staphylococcus aureus colonization was similar in all three cohorts.ConclusionA 2 + 1 PCV7 schedule implemented in South Africa was temporally associated with reduced risk of vaccine-serotype colonization compared to historically unvaccinated children. Also, vaccine-serotype acquisition rate using the 2 + 1 schedule was similar to that in the 3 + 1 dosing cohort, suggesting that similar indirect protection against pneumococcal disease could be derived from either schedule in South Africa.     

Social Determinants of Breastfeeding in the United States

Despite overall improvement in breastfeeding in the past 3 decades in the United States, significant and alarming social disparities persist. Adverse social determinants of health are increasingly recognized as root causes of social disparities in health outcomes, including breastfeeding initiation and continuation. We provide an overview of the evidence and mechanisms by which social determinants of health, including education, employment, food, neighborhood, and housing contribute to ongoing social disparities in breastfeeding in the United States, including current research gaps. We also review the intersection of social determinants of health with income, racism, and theory of planned behavior, a commonly used decision-making framework for breastfeeding promotion. Future interventions to address social determinants of breastfeeding should occur at the policy, community, organization, and individual levels.     

Insights into gastrointestinal microbiota-generated ginsenoside metabolites and their bioactivities

Abstract

The gastrointestinal microbiota and host co-evolve into a complex ‘super-organism,’ and this relationship plays a vital role in many physiological processes, such as drug metabolism. Ginseng is an important medicinal resource and the main ingredients are ginsenosides, which are less polar, difficult to absorb, and have low bioavailability. However, studies have shown that the biological activity of ginsenosides such as compound K (CK), ginsenoside Rg3 (Rg3), ginsenoside Rh2 (Rh2), 20(S)-protopanaxatriol (20(S)-PPT), and 20(S)-protopanaxadiol (20(S)-PPD) is closely related to the gastrointestinal microbiota. In this paper, the metabolic pathway of gastrointestinal microbiota-generated ginsenosides and the main pharmacological effects of these metabolites are discussed. Furthermore, our study provides a new insight into the discovery of novel drugs. Specifically, in new drug screening process, candidates with low biological activity and bioavailability should not be excluded. Because their metabolites may exhibit good pharmacological effects due to the involvement of the gastrointestinal microbiota. In addition, in further research studies to develop probiotics, a combination of agents could exert greater efficacy than single agents. Moreover, differences in lifestyle and diet lead to differences in the gastrointestinal microbiota in the human body. Therefore, administration of the same drug dose to different individuals could elicit different therapeutic effects, owing to the involvement of the gastrointestinal microbiota. Thus, treatment accuracy could be achieved by detecting the gastrointestinal microbiota before drug treatment.

• Highlights

• Gastrointestinal microbiota plays a decisive role in bioactivities of ginsenosides.

• The metabolic pathway and main pharmacological effects of ginsenoside metabolites are discussed.

• It provides new insights into novel drug discovery and further research to find probiotic, combinations to exert greater efficacy.

• Differences in lifestyle and diet, varies the gastrointestinal microbiota in the human body. However, the same dose of a drug producing different therapeutic effects may involve gastrointestinal microbiota.

     

Platelet/Lymphocyte Ratio Is Superior to Neutrophil/Lymphocyte Ratio as a Predictor of Chemotherapy Response and Disease-free Survival in Luminal B-like (HER2−) Breast Cancer

BackgroundThe neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been associated with the prognosis in breast cancer (BC). The relationship of the NLR and PLR with chemotherapy sensitivity and prognosis in luminal B-like (human epidermal growth factor receptor 2-negative [HER2⁻]) BC are not well studied.Patients and MethodsThe clinical data from 980 patients with luminal B-like (HER2⁻) BC from June 2012 to June 2016 were collected. The differences among the variables were calculated using the χ² test. The associations among the clinicopathologic factors, pretreatment NLR, pretreatment PLR, and disease-free survival (DFS) were analyzed using Kaplan-Meier curves and Cox analyses.ResultsThe median follow-up was 37 months (range, 5-77 months). For the 480 patients who had received neoadjuvant chemotherapy, low pretreatment PLR values were associated with higher pathologic complete response (pCR) rates compared with the high PLR group (15.8% for low vs. 9.2% for high PLR group; P = .027). Multivariate analyses showed that larger tumors, a greater number of lymph nodes involved, a high Ki-67 score, and a high PLR were independent prognostic factors of worse outcomes for the patients with luminal B-like (HER2⁻) BC. The risk of metastasis and/or recurrence was greater for the high PLR group than for the low PLR group (hazard ratio, 1.576; 95% confidence interval, 1.039-2.390; P = .032). The pretreatment NLR showed no such associations among this cohort of patients.ConclusionsThe results of the present study have shown that the pretreatment PLR is superior to the NLR as a predictor of pCR and DFS outcomes in patients with luminal B-like (HER2⁻) BC. A low pretreatment PLR was associated with higher pCR rates after neoadjuvant chemotherapy and was an independent predictive factor for better DFS outcomes among patients with luminal B-like (HER2⁻) BC.