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.

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

OBJECTIVE To explore the clinical characteristics of the neonates with early-onset sepsis caused by Listeria monocytogenes and analyze the risk factors for adverse treatment outcomes.METHODS A total of 16 neo-nates with early-onset sepsis caused by L.monocytogenes who were treated in neonatology department of the Affili-ated Suzhou Hospital of Nanjing Medical University from Jan.2012 to Dec.2023 were recruited as the research subjects.The clinical data and the results of laboratory test and drug susceptibility testing were collected from the neonates,and the risk factors for the adverse prognosis were analyzed.RESULTS Totally 14 neonates were born in the hospital,and the incidence rate was 6.7/100,000;13 cases were preterm infants,accounting for 81.25％.The peak of the onset ranged between May and November.Most of the 16 neonates showed clinical symptoms instantly after the birth,and the major manifestations included gasping and moaning(12 cases),hypotonia(11 cases),pale skin(10 cases)and poor response(9 cases).Totally 14 neonates showed the rise of C-reactive protein(CRP)in varying degree within 6 hours after the birth.In terms of the treatment outcomes,9 cases were cured and dis-charged,2 cases were improved and discharged,and 4 cases died.One of another cases was improved and died due to poor prognosis after against-advice discharge.There were significant differences in the decline of base excess,septic shock,use of sensitive antibiotics in early stage,invasive mechanical ventilation and peak value of CRP be-tween the survival group and the death group(P＜0.05).All of the L.monocytogenes were tested resistant to ce-foxitin,6 to ampicillin,6 to vancomycin,8 to linezolid.CONCLUSIONS The early-onset sepsis caused by L.mono-cytogenes is common among the preterm neonates and is prevalent in summer and autumn.Most of the cases show the symptoms instantly after the birth,the clinical manifestations are usually severe,and the mortality rate is high.The pregnant women who are suspected for L.monocytogenes infection before the delivery can be treated with penicillin,the neonates can be treated with the first choice of penicillin or ampicillin,and the severe cases can be treated with combination of vancomycin and linezolid.

In 2024, a total of 27 309 cases of medication error (ME) from 484 hospitals in 27 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. Among them, 279 (1.02%) were classified as grade A, 22 081 (80.86%) as grade B, 4 268 (15.63%) as grade C, 472 (1.73%) as grade D, 96 (0.35%) as grade E, 105 (0.38%) as grade F, 6 (0.02%) as grade H, and 2 (<0.01%) as grade I; no MEs of grade G occurred. Among the 27 030 patients involved in MEs of grade B to I, 15 124 (55.95%) were male and 11 906 (44.05%) were female; their ages were from 1 day to 104 years; 3 369 (12.46%) were children (<18 years old), 12 113 (44.81%) were young and middle-aged adults (≥18 to <60 years old), and 11 548 (42.72%) were elderly (≥60 years old). The top 3 contents of ME were wrong drug class (5 347 cases, 19.13%), wrong dosage (4 913 cases, 17.58%), and wrong administration frequency (3 429 cases, 12.27%). Among the 27 030 grade B-I MEs, the main person who triggered the event were physicians (18 703 cases, 69.19%) and pharmacists (6 343 cases, 23.47%). These MEs mainly occurred in clinics (11 009 cases, 40.73%), in hospital wards (7 393 cases, 27.35%), and in pharmacies (6 219 cases, 23.27%). The main persons who discovered the MEs were pharmacists (21 021 cases, 74.14%). The top 3 factors causing ME were lack of related pharmacologic knowledge (8 716 cases, 26.49%), tiredness (5 755 cases, 17.49%), and inexperienced skills (4 505 cases, 13.69%). A total of 209 patients were involved in severe MEs (grade E-I), including 133 (63.64%) males and 76 (36.36%) females, aged from 21 months to 94 years, of which 42 (20.10%) were children, 75 (35.88%) were young and middle-aged adults, and 92 (44.02%) were elderly. The top 3 diseases diagnosed in severe MEs were drug poisoning (41 cases, 19.62%), diabetes (34 cases, 16.27%), and hypertension (14 cases, 6.70%); the main person who triggered the MEs were patients and their families (135 cases, 64.59%); the MEs occurred mainly in patients′ houses (116 cases, 55.50%). Drug poisoning was mainly related to accidental ingestion by children, and MEs in patients with diabetes and hypertension were often related to issues on patient compliance. Based on the data of MEs in 2024, it was proposed to establish a better medication safety culture and improve the ME reporting situation in China, pay attention to the risks of misusing external drugs for internal use, children′s accidental ingestion and insulin-related MEs, strengthen the prevention of MEs related to look-alike sound-alike drugs, pay attention to the post administration management and the compliance education of home care for patients with chronic diseases, so as to improve the medication safety of patients in China.

OBJECTIVE To explore the clinical characteristics of the neonates with early-onset sepsis caused by Listeria monocytogenes and analyze the risk factors for adverse treatment outcomes.METHODS A total of 16 neo-nates with early-onset sepsis caused by L.monocytogenes who were treated in neonatology department of the Affili-ated Suzhou Hospital of Nanjing Medical University from Jan.2012 to Dec.2023 were recruited as the research subjects.The clinical data and the results of laboratory test and drug susceptibility testing were collected from the neonates,and the risk factors for the adverse prognosis were analyzed.RESULTS Totally 14 neonates were born in the hospital,and the incidence rate was 6.7/100,000;13 cases were preterm infants,accounting for 81.25％.The peak of the onset ranged between May and November.Most of the 16 neonates showed clinical symptoms instantly after the birth,and the major manifestations included gasping and moaning(12 cases),hypotonia(11 cases),pale skin(10 cases)and poor response(9 cases).Totally 14 neonates showed the rise of C-reactive protein(CRP)in varying degree within 6 hours after the birth.In terms of the treatment outcomes,9 cases were cured and dis-charged,2 cases were improved and discharged,and 4 cases died.One of another cases was improved and died due to poor prognosis after against-advice discharge.There were significant differences in the decline of base excess,septic shock,use of sensitive antibiotics in early stage,invasive mechanical ventilation and peak value of CRP be-tween the survival group and the death group(P＜0.05).All of the L.monocytogenes were tested resistant to ce-foxitin,6 to ampicillin,6 to vancomycin,8 to linezolid.CONCLUSIONS The early-onset sepsis caused by L.mono-cytogenes is common among the preterm neonates and is prevalent in summer and autumn.Most of the cases show the symptoms instantly after the birth,the clinical manifestations are usually severe,and the mortality rate is high.The pregnant women who are suspected for L.monocytogenes infection before the delivery can be treated with penicillin,the neonates can be treated with the first choice of penicillin or ampicillin,and the severe cases can be treated with combination of vancomycin and linezolid.

In 2024, a total of 27 309 cases of medication error (ME) from 484 hospitals in 27 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. Among them, 279 (1.02%) were classified as grade A, 22 081 (80.86%) as grade B, 4 268 (15.63%) as grade C, 472 (1.73%) as grade D, 96 (0.35%) as grade E, 105 (0.38%) as grade F, 6 (0.02%) as grade H, and 2 (<0.01%) as grade I; no MEs of grade G occurred. Among the 27 030 patients involved in MEs of grade B to I, 15 124 (55.95%) were male and 11 906 (44.05%) were female; their ages were from 1 day to 104 years; 3 369 (12.46%) were children (<18 years old), 12 113 (44.81%) were young and middle-aged adults (≥18 to <60 years old), and 11 548 (42.72%) were elderly (≥60 years old). The top 3 contents of ME were wrong drug class (5 347 cases, 19.13%), wrong dosage (4 913 cases, 17.58%), and wrong administration frequency (3 429 cases, 12.27%). Among the 27 030 grade B-I MEs, the main person who triggered the event were physicians (18 703 cases, 69.19%) and pharmacists (6 343 cases, 23.47%). These MEs mainly occurred in clinics (11 009 cases, 40.73%), in hospital wards (7 393 cases, 27.35%), and in pharmacies (6 219 cases, 23.27%). The main persons who discovered the MEs were pharmacists (21 021 cases, 74.14%). The top 3 factors causing ME were lack of related pharmacologic knowledge (8 716 cases, 26.49%), tiredness (5 755 cases, 17.49%), and inexperienced skills (4 505 cases, 13.69%). A total of 209 patients were involved in severe MEs (grade E-I), including 133 (63.64%) males and 76 (36.36%) females, aged from 21 months to 94 years, of which 42 (20.10%) were children, 75 (35.88%) were young and middle-aged adults, and 92 (44.02%) were elderly. The top 3 diseases diagnosed in severe MEs were drug poisoning (41 cases, 19.62%), diabetes (34 cases, 16.27%), and hypertension (14 cases, 6.70%); the main person who triggered the MEs were patients and their families (135 cases, 64.59%); the MEs occurred mainly in patients′ houses (116 cases, 55.50%). Drug poisoning was mainly related to accidental ingestion by children, and MEs in patients with diabetes and hypertension were often related to issues on patient compliance. Based on the data of MEs in 2024, it was proposed to establish a better medication safety culture and improve the ME reporting situation in China, pay attention to the risks of misusing external drugs for internal use, children′s accidental ingestion and insulin-related MEs, strengthen the prevention of MEs related to look-alike sound-alike drugs, pay attention to the post administration management and the compliance education of home care for patients with chronic diseases, so as to improve the medication safety of patients in China.

OBJECTIVES: To investigate the correlation of serum levels of bridging integrating factor 1 (BIN1) with acute myocardial infarction (AMI) and Killip class of the patients. METHODS: We retrospectively collected the data from 94 patients with AMI and 30 healthy individuals for analysis of the correlations of serum BIN1 levels with Killip class, TIMI scores, and neutrophil-to-lymphocyte ratio (NLR). We also assessed the diagnostic value of BIN1 combined with NLR for AMI. RESULTS: Serum BIN1 levels were significantly lower in AMI patients than in the healthy individuals (P=0.032). The AMI patients with Killip class I had significantly lower serum BIN1 levels than the healthy individuals (P=0.008). Serum BIN1 level was an independent predictor of AMI with a predictive value of 0.630 (95% CI: 0.513-0.748) at the optimal cutoff level of 0.341 ng/mL, a specificity of 50%, and a sensitivity of 78.5%. Serum BIN1 level was also an independent predictor for Killip class I group in the AMI patients with a predictive value of 0.672 (95% CI: 0.548-0.797) at the optimal cutoff level of 0.287 ng/mL, a specificity of 74.1%, and a sensitivity of 60%. For AMI diagnosis, the combination of NLR and serum BIN1 level had a predictive value of 0.811 (95% CI: 0.727-0.895) at the optimal cutoff level of 0.548 ng/mL, with a specificity of 92.6% and a sensitivity of 62.2%. There was a positive correlation between serum BIN1 level and TIMI score in AMI patients (r=0.186, P=0.003). CONCLUSIONS BIN1 is correlated with AMI and can be helpful for predicting short-term prognosis of the patients, and BIN1 combined with NLR has a high diagnostic value for AMI.
Humans ; Myocardial Infarction/diagnosis* ; Tumor Suppressor Proteins/blood* ; Adaptor Proteins, Signal Transducing/blood* ; Retrospective Studies ; Nuclear Proteins/blood* ; Lymphocytes/cytology* ; Neutrophils/cytology* ; Female ; Male ; Prognosis ; Middle Aged

AIM:To investigate the effect of a disintegrin and metalloproteinase(ADAM)domain-like decy-sin 1(ADAMDEC1)knockdown on the proliferation,migration and invasion of pancreatic carcinoma cells.METHODS:Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online da-tabases.Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcino-ma cell lines(MIA PaCa-2 and PANC-1)and pancreatic ductal cell line(hTERT-HPNE).The effects of ADAMDEC1 knockdown on cell proliferation,migration and invasion were evaluated using CCK-8,colony formation,wound-healing and Transwell assays.Additionally,Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers,as well as Wnt/β-catenin signaling pathway-related proteins in pancre-atic carcinoma cells.Furthermore,a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling path-way agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migra-tion.RESULTS:(1)ADAMDEC1 was highly expressed in pancreatic carcinoma cells.(2)Knockdown of ADAMDEC1 led to a significant reduction in the proliferation,migration and invasion of pancreatic carcinoma cells.(3)Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9,N-cadherin and vimentin proteins,alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related pro-teins.(4)Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation,migration,and invasion.CONCLUSION:ADAMDEC1 is highly expressed in pancreatic carcinoma.Targeted silencing of ADAMDEC1 has the potential to inhibit the prolifera-tion,migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway.

OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

Objective:To explore the expression levels of adrenomedullin (ADM) in follicular fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with ovarian function and inflammation.Methods:To conduct a cohort study, the data on infertile couples who received an antagonistic regimen of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) to promote ovulation from March to December 2023 at the Reproductive Medicine Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) were collected. PCOS patients were selected as the PCOS group, and patients who underwent IVF/ICSI assisted pregnancy solely due to tubal and/or male factors during the same period were selected as control group. The general clinical data of two groups of patients were analyzed, and the expression of ADM, interleukin 1β (IL-1β), IL-18, transforming growth factor β (TGF-β) in the follicular fluid were compared between the two groups of patients. And taking the concentration of ADM in follicular fluid as the main research indicator, correlation and multiple linear regression analysis were conducted with other indicators. Simultaneously the ADM mRNA expression, cell cycle and cell apoptosis of granulosa cells were compared between the two groups. Results:This study included 20 cases in the PCOS group and 20 cases in control group. Compared with control group, the expression of ADM in follicular fluid and granulosa cells of patients with PCOS were significantly lower (both P<0.001), while its testosterone, the ratio of luteinizing hormone and follicle-stimulating hormone, antral follicle count (AFC), number of retrieved eggs, ovarian sensitivity index, as well as IL-1β, IL-18 and TGF-β in follicular fluid were higher and negatively correlated with ADM ( r=-0.37, P=0.019; r=-0.32, P=0.047; r=-0.50, P<0.001; r=-0.38, P=0.017; r=-0.38, P=0.016; r=-0.44, P=0.005; r=-0.37, P=0.018; r=-0.54, P<0.001). Multiple linear regression showed that AFC, gonadotropin initiation dose, IL-1β and TGF-β were the independent related factors that affect local ADM levels ( r=-0.37, P=0.008; r=-0.27, P=0.035; r=-0.28, P=0.028; r=-0.45, P<0.001). There was no statistically significant difference in the cell cycle of granulocytes between the two groups ( P>0.05), but the apoptosis rate (AR) of granulocytes was higher in the PCOS group than in control group (median AR in the PCOS group was 46.07%, median AR in control group was 28.57%, n=10, P=0.036). Conclusion:The decreased expression of ADM in follicles of PCOS patients is related to ovarian endocrine disorders, multiple vesicles, high ovarian responsiveness and local inflammatory status.