Messenger RNA (mRNA) therapeutics involve delivering in vitro transcribed mRNA into specific cells to produce target proteins for the treatment or prevention of diseases. However, the development of mRNA therapeutics relies largely on mRNA delivery systems. Lipid nanoparticles (LNPs) represent the most widely used mRNA carriers in clinical applications. Composed of ionizable lipids, zwitterionic phospholipids, cholesterol, and polyethylene glycol-lipids, LNPs can address critical challenges in mRNA drug development, such as poor in vivo stability and the difficulty in crossing biological barriers. Ultimately, LNPs enable safe, efficient, and targeted mRNA delivery to the liver, lung, spleen, and other organs. This review outlines the roles of the four lipid components in LNPs for mRNA delivery. It then introduces targeted mRNA delivery to various organs/tissues such as the liver, lung, spleen, pancreas, bone marrow, and placenta, using strategies such as antibody modification, lipid structure alteration, and specialized administration routes. Additionally, this review discusses the applications and challenges of LNP-based mRNA therapeutics in disease treatment, aiming to provide insights for the clinical translation of mRNA therapies and for further innovations in LNP delivery systems.
Humans ; RNA, Messenger/administration & dosage* ; Nanoparticles/chemistry* ; Lipids/chemistry* ; Drug Delivery Systems ; Animals ; Liposomes

Objective The aim of the paper is to monitor the natural infection of the viruses in ticks from the Gansu Province and elicit the risk of tick-borne viral disease transmission in the Silk Road Economic Zone.Methods The Wuwei area,where the Loess Plateau,the Tibetan Plateau and the Meng-Xin Plateau converge,was selected as a surveillance site to collect off-host or parasitic tick samples and detect the potential viruses harbored in them with meta-transcriptomic sequencing.The clean reads were assembled and annotated to explore the diversity of viruses under the genome phylogenetic analyses,identifying potential novel viruses.Results A total of 98 ticks of 5 species in 3 genera were sampled,including Dermacentor silvarum,Dermacentor nuttalli,Hyalomma asiaticum,Hyalomma scupense and Haemaphysalis kolonini.Among these tick samples,Mivirus shows the highest abundance,followed by Orthopoxvirus and Orthonairovirus.The assembled viral sequences were identical to Bole tick virus 1,Bole tick virus 3,Changping tick virus 1 and Taishun tick virus.Meanwhile,a novel subspecies of Bole tick virus 4 with 96.92%identity to the closest Flaviviridae sp.was detected and provisionally named"Bole-like tick virus 4"with pending characterization by isolation or other approaches.Conclusions The occurrence of diverse tick-borne viruses and potential novel viruses in the surveillance sites indicates that surveillance and preventive measures are warranted.

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

Alveolar echinococcosis is a parasitic zoonosis that severely damages human health. Currently, radical surgical resection is the first choice for hepatic alveolar echinococcosis. For the advanced hepatic echinococcosis patients with refractory radical resection, the palliative surgery combined with chemotherapy, liver transplantation, drug therapy, and radiofrequency microwave ablation may provide comprehensive tools. This article reviews the current situation and progress of comprehensive treatments for hepatic alveolar echinococcosis.

To study pharmacokinetic characteristics of epimedin A, B, C and icariin after intermuscular administration of Chuankezhi injection to rat. The established RRLC-MS/MS method was applied for simultaneous determination of four analytes in rat plasma and calculating their pharmacokinetic parameters. As a result, each analyte showed a good linear relationship in the concentration range of 1-1 000 μg•L⁻¹.The intra-day precise was 96.9%-107.5% with RSD<5.99%, inter-day precise was 92.3%-105.0% with RSD<10.16%. The relative recovery of four analytes was 88.1%-101.1% with RSD<7.9% and their absolute recovery was 72.0%-86.6% with RSD<6.3%. After intermuscular administration of Chuankezhi injection, the plasma concentration of four flavonoid glycosides rapidly arose to peaks at about 10 min, and then quickly declined in rat. Tmax of epimedin A, B, C and icariin was 0.21, 0.19, 0.16 and 0.49 h, respectively, and their mean elimination half-life(t1/2z) was 0.60, 0.62, 0.47 and 0.49 h. The established method was validated to be sensitive, rapid and specific for determination of the four analytes. Serum concentration of 4 species of epimedium flavonoids in Chuankezhi injection was low, and their absorption and elimination seem quickly, displaying similar pharmacokinetic characteristics in this study.

A quantitative method for epimedin A, B, C and icariin in rat plasma was established using LC-MS/MS after intermuscular administration of Chuankezhi injection to rat. Chromatographic separation was performed on an Agilent Eclipse XDB-C₁₈ column (150 mm×2.1 mm, 5.0 μm) at 40℃. Mobile phase consisted of acetonitrile -0.1% formic acid in water (35:65), and the flow rate was 0.22 mL·min^-1. The LC effluent was detected and analyzed using an ESI-triple quadrupole tandem mass spectrometer under the multiple reaction monitoring (MRM) in the negative ion mode. The plasma samples were treated with solid phase extraction prior to LC-MS/MS analysis. As a result, all of the four analytes displayed a good linearity over the concentration of 1-1000 ng·mL^-1. The RSDs of intra-day and inter-day assays were less than 5.99% and 10.16%, respectively. The relative recovery of each analyte was between 88.1%-101.1% with RSD<7.9% and the absolute recovery was between 72.0%-86.6% (RSD<6.3%). In conclusion, the established method shows good specificity, sensitivity and efficiency for quantifying the four flavonoid glycosides contained in rat plasma.

OBJECTIVETo investigate the effect of the escharectomy during burn shock stage on expression of glucose translator-4 (GLUT4) mRNA in skeletal muscle and adipose tissue.

METHODS30% TBSA scalded rats were employed. Escharectomy were conducted at 8 h, 24 h, 168 h after burns respectively. Insulin, glucagon, cortisol and glucose levels in serum were analyzed. RT-PCR were employed to analyze GLUT4 mRNA expression in skeletal muscle and adipose tissue.

RESULTSGlucagon, cortisol and glucose levels in serum were declined in groups which escharectomy were conducted during burn shock stage. GLUT4 mRNA expression in both skeletal muscle and adipose tissue were downregulated after burns and escharectomy conducted during burn shock stage made it restored to near normal.

CONCLUSIONGLUT4 mRNA expression will declined after major burns in skeletal muscle and adipose tissue. Escharectomy during shock stage could make it upregulated, which will be helpful to improve glucose metabolism and hypermetabolism after major burns.

Adipose Tissue ; metabolism ; Animals ; Blood Glucose ; Burns ; physiopathology ; surgery ; Gene Expression ; Glucagon ; blood ; Hydrocortisone ; blood ; Insulin ; blood ; Male ; Monosaccharide Transport Proteins ; genetics ; Muscle, Skeletal ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Shock, Traumatic ; physiopathology