Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

Effects of a closed-loop system against SARS-CoV-2 at the Beijing 2022 Olympic Winter Games:a descriptive and modeling study

BACKGROUND:To assess the efficacy of the epidemic prevention measures of the“closed-loop”system adopted by the Beijing 2022 Olympic Winter Games(BOWG).METHODS:We retrospectively collected and analyzed information,including age,sex,nationality,vaccination status,date of diagnosis,and date of entry,from 280 SARS-CoV-2-positive individuals identified during the BOWG.A susceptibility-exposed-infectious-remove model was employed to evaluate the effectiveness of epidemic prevention strategies on controlling the spread of SARS-CoV-2 under different scenarios during the BOWG.RESULTS:Regarding SARS-CoV-2-positive cases,97.9%were imported,and 96.4%were asymptomatic.The median age was 37 years(range:29–47 years),and 73.9%were male,with the majority of cases being broadcasters and European attendees.Regarding vaccination status,93.5%were fully vaccinated,and six cases were considered to have been infected in the closed-loop system during the BOWG.Assuming that the BOWG adopted a semi-closed-loop management system,the cumulative number of confirmed cases would be 1,137 for quick quarantine measures(3 d later)implemented and 5,530 for delayed quarantine measures(9 d later)implemented.This modeling revealed that stringent pandemic prevention measures and closed-loop management effectively controlled the spread of SARS-CoV-2 during the BOWG.CONCLUSION:Imported cases are considered the main risk factor for SARS-CoV-2 transmission during mass gatherings,but a comprehensive closed-loop system could minimize transmission among attendees and general personnel.

Cardiopulmonary resuscitation and termination of resuscitation on out-of-hospital cardiac arrest in China

To the Editor: Out-of-hospital cardiac arrest (OHCA) is a major public health challenge. Early initiation, good quality cardiopulmonary resuscitation (CPR), and the use of an automated external defibrillator (AED) have been reported to significantly improve the survival and long-term outcomes in survivors of OHCA.

Association between duration of return of spontaneous circulation and outcomes after out-of-hospital cardiac arrest

Background:Return of spontaneous circulation(ROSC)is a core outcome element of cardiopulmonary resuscitation(CPR);however,the definition or criterion of ROSC is disputed and varies in resuscitation for out-of-hospital cardiac arrest(OHCA).Methods:This was a retrospective study of 126 patients with OHCA who achieved ROSC between January and December 2020.The probability of survival after OHCA related to CPR and ROSC duration was analyzed using the probability density function and empirical cumulative density functions.Results:There were no significant differences between ROSC sustained until emergency department arrival and that sustained for at least 20 minutes in terms of the 24-hour survival rate(31.3%[31/99]vs.35.7%[10/30];P=0.84),30-day survival rate(23.2%[23/99]vs.25.0%[7/30];P=0.99),or survival at 30 days with cerebral performance category(CPC)1 and 2(18.2%[18/99]vs.10.7%[3/30];P=0.44).The Kolmogorov-Smirnov test values from the empirical cumulative density functions with ROSC sustained until hospital arrival and that sustained for at least 20 minutes were 0.44,0.20,and 0.24 for CPC 1 or 2,CPC 3 or 4,and CPC 5,respectively.Conclusion:Return of spontaneous circulation is a core outcome element of CPR.It should be defined as sustained for at least 20 minutes or until arrival at the emergency department and as a basic standard for evaluating resuscitation success after OHCA.