RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Platelet transfusion refractoriness (PTR) is one of the common problems in platelet transfusion, significantly impacting patient clinical outcomes and increasing the demand for allogeneic platelet transfusion. Both immune and non-immune factors contribute to PTR, among which the occurrence mechanism of immune platelet transfusion refractoriness (IPTR) involves humoral and cellular immune processes and is influenced by platelet storage, processing, and the patient's disease, therapy and immune status. This review comprehensively discusses the research related to the factors for alloimmune of IPTR, the mechanism of platelet clearance and its influencing factors. Furthermore, it explores feasible prevention and treatment measures such as platelet compatibility transfusion and clinical treatments. The aim is to provide a systematic cognition for a deeper understanding of the pathological process of platelet alloimmunization and clearance, and to provide a theoretical basis for the construction of precise clinical prevention and treatment strategies for IPTR, as well as to explore feasible research directions in this field in the future.

Objective:To identify the factors associated with the care needs of the older adults aged 65-105 by age groups,and to compare these factors across different age groups.Methods:A total of 12 244 older adults from the Chinese longitudinal healthy longevity survey(CLHLS)conducted in 2018 were included in the analyses.The participants were categorized into three age groups:young-old(aged 65-79),middle-old(aged 80-89),and oldest-old(aged 90-105).The level of disability was measured by the disability index(DI)in four dimensions,reflecting their care needs.Potential factors associated with care needs were selected based on the health ecological model(HEM),including per-spectives of personal characteristics,behavioral characteristics,interpersonal network,living and working conditions,and policy environment.Multifactor analysis was performed using multinomial Logistic regres-sion.Results:Among China's 12 244 older adults,43.4％had medium or high care needs.Factors for higher care needs of older adults included higher age,higher number of chronic diseases,no exercise habit,excessive sleep duration(≥9 h/d),depressive tendency,living with children or spouse,and un-educated(all P＜0.05).In addition,the young-old group who were past smokers(OR=2.009,95％CI:1.019-3.959),were past drinkers(OR=2.213,95％CI:1.141-4.291),and reported self-per-ceived poverty(OR=2.051,95％CI:1.189-3.540),had higher level of care needs.The middle-old group who were female(OR=1.373,95％CI:1.038-1.817),never drank alcohol(OR=1.551,95％CI:1.059-2.269),and were lack of medical insurance(OR=1.598,95％CI:1.053-2.426),and had higher level of care needs.The oldest-old group who were female(medium care needs vs.low care needs:OR=1.412,95％CI:1.062-1.878;high care needs vs.low care needs:OR=1.506,95％CI:1.137-1.993),reported self-perceived poverty(OR=2.064,95％CI:1.282-3.323),and were lack of medical insurance(OR=1.621,95％CI:1.148-2.291),and had higher level of care needs.Conclusion:The identical factors associated with care needs across different age groups include age,chronic disease,exercise,sleep,depression,living arrangement,and education.Smoking,alcohol consumption,and economic status are specific factors among the young-old group of the older adults,while gender and medical insurance are specific factors among the middle-old and the oldest-old group of the older adults.We recommend conducting prospective cohort studies and intervention studies among specific age groups on the above factors to provide reliable evidence for policy formulation.

Objective:To construct and prepare recombinant virus strains chimeric with human metapneumovirus (HMPV) antigenic epitopes.Methods:Recombinant influenza virus vectors which chimeric with different HMPV antigenic epitopes were rescued by reverse genetics using eight-plasmid system. The recombinant influenza virus strain used the internal genes of A/PR/8/34 (PB1, PB2, PA, NP, NS, M, HA, and NA) as a backbone, with concomitant genetic modifications to insert the B-cell epitopes of HMPV into the HA gene, and the CTL+ Th cell epitopes of HMPV into the NA gene. Preparation of recombinant influenza virus strains using reverse genetics in a " 7+ 1" model. The recombinant virus strains were evaluated by measuring hemagglutinin (HA) titers, half tissue culture infectious dose (TCID 50) and growth curves. Sequencing analysis was conducted to verify whether the rescued viruses carried the chimeric HMPV epitopes. Results:The epitopes of HMPV were inserted into the influenza virus genome and two recombinant influenza virus strains were rescued successfully, named as FLU/HMPV/B and FLU/HMPV/CTL+ Th. HA titers of the recombinant strains were both 2 7, their TCID 50 were 10 5.2/ml and 10 5.0/ml, respectively. After cultured for three passages in chick embryo, these two recombinant strains could proliferate steadily. Whole genome sequencing verified that the FLU/HMPV/B carried the B-cell epitopes of HMPV, the FLU/HMPV/CTL+ Th carried the CTL and Th cell epitopes of HMPV. Growth curve tests also verified that the recombinant strains could proliferate steadily in eggs. Conclusions:Two recombinant influenza virus vector strains carrying the B cell, CTL and Th epitopes of HMPV were rescued successfully. The result of the recombinant virus strains in terms of growth characteristics as well as genetic stability indicate that they meet the requirements for proceeding to the next step of animal experiments. The immunogenicity and immunoprotective effect will be further evaluated by mouse experiments. Ultimately new ideas for the realization of " one vaccine for two uses" or " one vaccine formultiple uses", as well as a new strategy for the development of HMPV vaccine will be proposed.

OBJECTIVE To develop the evaluation system for the readability of drug instructions based on Chinese patient needs， and to provide scientific evidence for improving the readability of drug instructions in China. METHODS The literature review and expert consultation were adopted to establish the evaluation index system for the readability of drug instructions. Then， by the analytic hierarchy process， the index weight in the evaluation system was determined， and the evaluation system for the readability of drug instructions was established. Fuzzy comprehensive evaluation was used to test the evaluation system， taking drug instruction of Dexamethasone acetate cream as an example. RESULTS The evaluation system for the readability of drug instructions was established with 5 primary criteria such as text expression， numerical application， content design， behavioral suggestions， and layout design， as well as 17 sub-criteria such as easy-to-understand words and appropriately long sentences. The reliability and validity tests met the requirements. The result of 100 respondents evaluating the readability of the drug instructions of Dexamethasone acetate cream showed that the readability of drug instructions was scored as good as 4.24. CONCLUSIONS Established evaluation system for the readability of drug instructions in the study can be used to evaluate the quality and readability of drug instructions in China.

Objective To analyze and evaluate the implementation effect of tuberculosis prevention and control program in Wuhan, and to provide reference for scientific formulation of tuberculosis prevention and control measures. Methods Using the National Tuberculosis Information Management System, descriptive statistical analysis was carried out on the medical record information of pulmonary tuberculosis patients registered in Wuhan , 2016 - 2021. Results A total of 34 937 cases of pulmonary tuberculosis were registered in Wuhan , with an average annual incidence rate of 49.85/100 000. The incidence rate showed a downward trend year by year, with a statistically significant difference in 2016—2021 (χ²_trend = 708.387, P<0.001). The patients mainly came from referrals, accounting for 71.86%, and the proportion of referrals varied significantly among different years (χ²=355.541, P<0.001). The diagnosis type was mainly pathogenic negative, accounting for 49.12%. The proportion of pathogenic negative had statistically significant difference among different years (χ²=1 354.830, P<0.001). The proportion of patients cured and completed the course of treatment reached 93.98%, with statistically significant differences in the proportions among different years (cured, χ²=1 080.252, P<0.001; completed the treatment course, χ²= 933.655, P<0.001). The sputum examination rate of newly diagnosed patients in each year reached over 90%, and the overall completion rate reached over 95%. The proportion of positive pathogens showed an increasing trend year by year. Conclusion The overall epidemic situation of tuberculosis in Wuhan is declining year by year, and tuberculosis prevention and control work has achieved remarkable results. Active screening in key areas and populations should be strengthened, and prevention and control strategies should be formulated by emphasizing the key and difficult points.