Ionizable drug delivery systems for efficient and selective gene therapy

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.

Diagnosis and treatment experience of atypical hepatic cystic echinococcosis type 1 at a tertiary center in China

BACKGROUND Some hydatid cysts of cystic echinococcosis type 1(CE1)lack well-defined cyst walls or distinctive endocysts,making them difficult to differentiate from simple hepatic cysts.AIM To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries.METHODS The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region(China)from January 2018 to September 2023 were retrospectively analyzed.Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis,routine abdominal ultrasound,high-frequency ultrasound,abdominal computed tomography(CT)scan,and laparoscopy.Subsequent to the treatments,these patients underwent reexaminations at the outpatient clinic until October 2023.The evaluations included the diagnostic precision of diverse examinations,the efficacy of surgical approaches,and the incidence of CE recurrence.RESULTS All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan.Among them,16 patients were preoperatively diagnosed with atypical CE1,and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound.All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy,of whom 14 patients were intraoperatively confirmed to have CE1,which was consistent with the postoperative pathological diagnosis,one patient was diagnosed with a mesothelial cyst of the liver,and the other was diagnosed with a hepatic cyst combined with local infection.Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts,4 received aspiration sclerotherapy of hepatic cysts,and 19 received laparoscopic fenestration.These patients were intraoperatively diagnosed with simple hepatic cysts.During the followup period,none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices.One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space.CONCLUSION Abdominal high-frequency ultrasound can detect CE1 hydatid cysts.The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE.

关节镜辅助下金属拉力螺钉配合可吸收螺钉治疗Hoffa骨折

目的评估在关节镜辅助下金属拉力螺钉配合可吸收螺钉治疗Hoffa骨折的临床疗效。方法对13例Hoffa骨折患者采取关节镜监视下撬搏复位,骨折复位满意后负重面采用可吸收螺钉埋头固定,非负重面采用金属拉力螺钉增强固定,同时Ⅰ期探查修复关节内其他损伤,术后行可调支具固定,早期进行非负重功能锻炼,定期随访并记录膝关节功能恢复程度。结果患者均获随访,时间8~24个月,平均随访13.6个月,术后切口均Ⅰ期愈合,内固定无松动、断裂,骨折骨性愈合,平均下地活动时间9.4周。按Hoffa骨折术后功能恢复评估标准综合评估膝关节功能恢复程度。优良12例,可l例,优良率为92.3%。结论关节镜辅助下金属拉力螺钉配合可吸收螺钉治疗Hoffa骨折,具有骨折复位满意、损伤小及固定牢固的优点,可Ⅰ期处理关节内其他损伤,明显降低膝关节僵硬程度,提高了患者生活质量。

Effects of postweld aging on the microstructure and properties of bobbin tool friction stir-welded 6082-T6 aluminum alloy

Samples of 6082-T6 aluminum alloy were subjected to bobbin tool friction stir welding (BT-FSW), and the joints were treated by postweld natural aging (PWNA) and postweld artificial aging (PWAA). The microstructure, microhardness, and tensile properties of the aged and as-welded specimens were investigated. Transmission electron microscopy (TEM) observations revealed that a large number of Guinier–Preston (GP) zones precipitated in the form of a network on the stir zone (SZ) after PWNA for 60 d, and a large number of β'' phases precipitated in the matrix for after PWAA for 6 h. As the aging time increased, the microhardness of the SZ and the thermomechanically affected zone (TMAZ) increased significantly, and the hardness of the SZ after PWAA for 6 h was close to that of the base metal (BM). With increasing PWNA time, the strength and strain increased slightly. When the PWAA time increased, the strength clearly increased, with a maximum value of 279.9 MPa after 6 h, while the strain decreased.