Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

Effectiveness of monoclonal antibody therapy for COVID-19 patients using a risk scoring system

IntroductionMonoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021.MethodsAccording to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan.ResultsDuring Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12–0.53) and 0.10 (95% CI: 0.01–0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event.ConclusionsThe administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.     

A candidate multi-epitope vaccine against porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae induces robust humoral and cellular response in mice

Porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (M. hyopneumoniae, Mhp) are two of the most common pathogens involved in the porcine respiratory disease complex (PRDC) resulting in significant economic losses worldwide. Vaccination is the most effective approach to disease prevention. Since PRRSV and Mhp co-infections are very common, an efficient dual vaccine against these pathogens is required for the global swine industry. Compared with traditional vaccines, multi-epitope vaccines have several advantages, they are comparatively easy to produce and construct, are chemically stable, and do not have an infectious potential. In this study, to develop a safe and effective vaccine, B cell and T cell epitopes of PRRSV-GP5, PRRSV-M, Mhp-P46, and Mhp-P65 protein had been screened to construct a recombinant epitope protein rEP-PM that has good hydrophilicity, strong antigenicity, and high surface accessibility, and each epitope is independent and complete. After immunization in mice, rEP-PM could induce the production of high levels of antibodies, and it had good immunoreactivity with anti-rEP-PM, anti-PRRSV, and anti-Mhp antibodies. The anti-rEP-PM antibody specifically recognizes proteins from PRRSV and Mhp. Moreover, rEP-PM induced a Th1-dominant cellular immune response in mice. Our results showed that the rEP-PM protein could be a potential candidate for the development of a safe and effective multi-epitope peptide combined vaccine to control PRRSV and Mhp infections.     

SLC及其受体CCR7与Ⅰ期非小细胞肺癌淋巴结微转移的相关性

目的 探讨溶质载体蛋白（SLC）及其受体趋化因子受体7（CCR7）与I期非小细胞肺癌（NSCLC）淋巴结微转移的相关性。方法 选取2019年1月~2020年3月于我院就诊的I期NSCLC患者127例为研究对象，按照淋巴结微转移情况分为对照组92例和转移组35例，所有患者入院后均通过根治术切除病灶，通过免疫组化方式检测病灶中SLC7A11及CCR7含量，并收集患者临床资料、实验室检查资料及影像学检查资料。通过Logistic回归分析评价SLC7A11及CCR7与淋巴结微转移之间的关系。最后通过建立ROC曲线分析两者及其联合检测对NSCLC患者微淋巴结转移的预测价值。结果 两组患者SLC7A11及CCR7表达水平存在显著差异（P＜0.05）。转移组患者病灶直径、支气管受累及TLG显著高于对照组（P＜0.05）。病灶直径（OR=49.254,95%CI=11.062~507.604）是影响NSCLC淋巴结微转移的独立危险因素（P＜0.05）。SLC7A11（OR=8.622）及CCR7（OR=8.709）表达水平是影响NSCLC淋巴结微转移的独立因素（P＜0.05）。SLC7A11、CCR7及联合诊断对NSCLC淋巴结微转移具有较好的检测价值（均P＜0.05）。联合检测特异度显著高于 SLC7A11及CCR7单独检测（2=7.292，15.125；均P＜0.01）。结论 SLC家族的中SLC7A11及其受体CCR7与NSCLC患者微淋巴结转移显著相关。     

滋肾育胎丸加减方预防ACA阳性者不良妊娠结局的效果及机制研究＊

目的 探讨滋肾育胎丸加减方预防抗磷脂抗体（ACA）阳性者不良妊娠结局的效果及机制研究。方法 选取2016年2月至2019年2月我院收治的89例ACA阳性，先兆性流产或有习惯性流产（RSA）史患者，将采用西医治疗的40例作为对照组，将采用西医联合滋肾育胎丸加减方治疗的49例作为观察组，比较两组中医证候疗效、中医证候积分、ACA-IgA、ACA-IgM、ACA-IgG、凝血指标［血小板聚集功能（PAF）、活化蛋白C（PC）、抗凝血酶（AT）、纤溶酶原激活抑制物-1（PAI-1）］、Th1/Th2细胞因子［干扰素γ（IFN-γ）、白介素-2（IL-2）、白介素-4（IL-4）、白介素-10（IL-10）］、妊娠结局、安全性。结果 治疗2周后检测ACA，观察组2例未降低，对照组11例未降低，观察组未降低患者占比低于对照组（P<0.05）；观察组总有效率100.00%高于对照组85.00%（P<0.05）；观察组治疗4周、7周后中医证候积分低于对照组（P<0.05）；观察组治疗4周、7周后ACA-IgA、ACA-IgM、ACA-IgG低于对照组（P<0.05）；观察组治疗4周、7周后PAF、PAI-1低于对照组，PC、AT高于对照组（P<0.05）；观察组治疗4周、7周后IFN-γ、IL-2低于对照组，IL-4、IL-10高于对照组（P<0.05）；观察组活产率95.92%高于对照组80.00%（P<0.05）；组间不良反应总发生率比较，差异无统计学意义（P>0.05）。结论 动态监测ACA对滋肾育胎丸加减方精准应用具有指导意义，指导滋肾育胎丸加减方通过调理脏腑、气血、经络功能，改善先兆性流产或有RSA史患者临床症状及凝血因子指标，降低ACA水平，并可改善患者免疫耐受功能，提高胎儿活产率，且安全性高。     

Out of the boxes,out of the silos: The need of interdisciplinary collaboration to reduce poor-quality medical products in the supply chain

In this paper, we argue that understanding and addressing the problem of poor-quality medical products requires a more interdisciplinary approach than has been evident to date. While prospective studies based on rigorous standardized methodologies are the gold standard for measuring the prevalence of poor-quality medical products and understanding their distribution nationally and internationally, they should be complemented by social science research to unpack the complex set of social, economic, and governance factors that underlie these patterns. In the following sections, we discuss specific examples of prospective quality surveys and of social science studies, highlighting the value of cross-sector partnerships in driving high-quality, policy-relevant research in this area.