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.

Objective To investigate the predictive value of combined plasma gluconic acid(GA),fumaric acid(FA),and pseudouridine levels at admission for acute kidney injury(AKI)in elderly patients with acute myocardial infarction(AMI).Methods A total of 78 elderly AMI patients transferred from Emergency Department to Coronary Care Unit in Fuwai Hospital during Decem-ber 2021 and July 2022 were enrolled in this prospective study.They were divided into AKI group(40 cases)and non-AKI group(38 cases)according to whether they developed AKI during hospi-talization.Plasma levels of GA,FA and pseudouridine were quantitatively detected with liquid chromatography-tandem mass spectrometry.ROC curve was plotted to assess the predictive value of these three plasma metabolites for AKI in AMI patients.Multivariate logistic regression analy-sis was applied to analyze the clinical risk factors for AKI.Results There were no statistical differences in the plasma levels of GA,FA and pseudouridine between the AKI group and the non-AKI group(P＞0.05).ROC curve analysis revealed that the plasma levels of the three indicators had no predictive value for the development of AKI in elderly AMI patients(AUC=0.576,95％CI:0.449-0.704,P=0.246;AUC=0.595,95％CI:0.467--0.721,P=0.154;AUC=0.563,95％CI:0.435-0.692,P=0.337).Multivariate logistic regression analysis revealed that left ventricu-lar ejection fraction(LVEF)was an independent predictor for AKI development in elderly AMI patients(OR=0.923,95％CI:0.870-0.978,P=0.007).Conclusion Plasma GA,FA and pseud-ouridine cannot predict the development of AKI in elderly AMI patients,while,LVEF is an inde-pendent predictor for the development.

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

Objective:To study the application effect of objective structured clinical examination (OSCE)-based situational simulation case teaching on Nursing Fundamentals practical training. Methods:Using convenient sampling method, two undergraduate nursing classes of Batch 2018 in Hubei University of Chinese Medicine were chosen as the study objects. They were divided into observation group with 45 students and control group with 43 students through ball touching method. The control group used traditional teaching method, on this basis, the observation group used OSCE-based situational simulation case teaching. At the end of the semester, the results of theoretical assessment, operational skills assessment, humanistic care, health education achievements of the two groups of nursing students and students’ evaluation of the new teaching method in the observation group. SPSS 22.0 was used for t test. Results:The sores of theoretical assessment, operational skills and humanistic care assessment in the observation group were (81.01±8.53), (92.69±3.87) and (11.73±1.59), and the corresponding sores in control group were (76.94±9.74), (91.21±2.70) and (10.79±1.36). The nursing students in the observation group had significantly higher scores than the control group in above mentioned aspects ( P<0.05). In the observation group, 45 students (100.0%) believed that this teaching method could stimulate learning interest and comprehensively deal with clinical problems, 43 students (95.6%) thought that this teaching method could improve team cooperation ability, only one person (2.2%) did not agree that this teaching method could help to form critical thinking, and 42 students (93.3%) said that the teaching hours of this teaching method could be appropriately increased. Conclusion:The OSCE-based situational simulation case teaching may effectively improve the teaching quality of the nursing students and mobilize their learning activities.

Objective To investigate the value of monochromatic curve features parameters in assessing various types of upper urinary calcium calculi in vivo on dual-energy CT(DECT).Methods Total 55 calcium calculi underwent dual-source CT in dual-energy mode were analyzed retrospectively.According to the result of infrared spectrometer,four types of calcium calculi were seen in this study:group 1(COM,12),group 2(COM+COD,9),group 3(COM+CaP,8),group 4(COM+COD+CaP,26).For each stone,mono-chromatic images from 40 keV to 190 keV(interval of 10 keV)were reconstructed.We used the different single spectral CT values and curve slope to differentiate of various types of calcium calculi.Results The parameters of the different single spectral CT values and curve slope were significantly different among the four groups.110 keV could differentiate the most groups.The curve slopes of group 1 with group 2 and group 3,group 2 with group 4,group 3 with group 4 were significantly different.Conclusion The spectral curve features parameters is helpful in the characterization of various types of calcium calculi.

Objective To explore the effect of the modular teaching for nursing students based on WeChat in the comprehensive training before the practice.Methods The undergraduate students of nursing were randomly divided into 5 classes,among which class 1,2,3 as the control group,and class 4,5 as the experimental group.The control group used the traditional ‘Case Teaching Method',taking the group as a unit to practice the clinical nursing skills individually;while the experimental group took the method which integrated individual nursing skills and practical materials with humanistic qualities in clinical cases.They conducted practical training by dividing the learning module with the ‘representative patients',using WeChat as the learning and exchange platform andbuilding modular training model.After the training,the results were evaluated by the score sheet for integrated skills,a critical-thinking scale and the learning model questionnaire.The data was analyzed by T-Test and Chi-Square inspection.Results All of the nursing students were willing to use WeChat for autonomous learning.The scores of the nursing students in the experimental group were higher than those in control group in the abilities of judgement,communication,operation and introspection.The difference was statistically significant (P＜0.05).In addition to the cognitive maturity,the scores of experimental group were higher than those in control group in the searching for truth,opening mind,abilities of analysis and integration and self-confidence in critical thinking and desire for knowledge,The difference was statistically significant (P＜0.05);Also the proportion of experimental group was higher than the control group in students' attitude to study,knowledge acquisition and practical training mode.The difference was statistically significant (P＜0.05).Conclusion The implementation of nodular teaching mode based on WeChat is beneficial to improve the clinical comprehensive ability of nursing students,and help to train the high quality nursing talents who meet the needs of clinical practice.

OBJECTIVETo explore the characteristics of mutations 4 common deafness-related genes among 216 patients from Shanghai area with non-syndromic hearing impairment (NSHI).

METHODSThirteen mutation sites in the four genes, namely GJB2 (c.35delG, c.176del16, c.235delC, c.299delAT, and c.155delTCTG), SLC26A4 (c.IVS7-2A>G, c.2168A>G, and c.1229C>T), mtDNA 12SrRNA (m.1494C>T, m.1555A>G, m.7445A>G, and m.12201T>C) and GJB3 (c.538C>T) were detected among the 216 patients and 41 individuals with normal hearing. The frequency and types of mutations were compared between the two groups.

RESULTSAmong the 216 NSHI patients, the total detection rate was 16.20% (35/216). GJB2 mutations were found in 17(7.87%) of the 216 patients, which included 5 cases with homozygous c.235delC mutation, 5 with homozygous c.235delC mutation, 1 with homozygous c.299delAT mutation, and 1 with homozygous c.299delAT mutation. c.235delC and 299delAT mutations were found in 5 cases. SLC26A4 mutation was found in 12(5.56%) of the 216 patients, which included 2 cases with homozygous c.IVS7-2A>G mutation, 9 with homozygous c.IVS7-2A>G mutation, and 1 with homozygous c.2168A>G mutation. Homogeneous mtDNA 12SrRNA m.1555A>G mutation was found in 6(2.78%) of the 216 patients. No GJB3 gene mutation was detected. No mutation of the 4 genes were detected in the 41 individuals with normal hearing. In 2 cases of the 12 patients with SLC26A4 gene mutation, CT scan of the temporal bone has confirmed expansion of vestibular aqueduct.

CONCLUSIONAbove results indicated that GJB2 and SLC26A4 were the major genes involved with hearing loss in Shanghai area.

Objective:To explore the effect of oxycontin combined with gabapentin on the clinical cure and immunity for patients with neuropathic cancer pain.Methods:80 patients with neuropathic cancer pain were enrolled in our hospital from June to 2016 July,of which patients divided into two groups randomly,Group A(n=40) accepted oxycontin treatment,and Group B (n=40) adopted gabapentin based on the patients in Group A.The VAS score and curative effect of the patients were compared between two groups;The quality of life of all patients were evaluated post-treatment,and the change of immunity indexes were compared and analyzed.Results:The VAS score of all patients was decreased significantly compared with pre-treatment (P＜0.05),and the score of Group B was lower than those patients in Group A (P＜0.05);The total remission rate of Group B was significantly higher than those of Group A (P＜0.05);after treatment,the score of appetite,emotion,sleep,daily activities,social communications of all patients decreased significantly compared with pre-treatment (P＜0.05),and the change of Group B was decrease significantly higher than those patients in Group A (P＜0.05);the immune index of two groups was significantly increased (P＜0.05),and the level of the indexes including IgG,IgA,IgM,CD4+,CD4+/CD8+ and circulating immune complex (CIC) increased compared with pre-treatment remarkably (P＜0.05),and which change in Group B was significantly higher than Group A (P＜0.05).Conclusions:Oxycontin combined with gabapentin for patients with neuropathic cancer pain deserved popularization in clinical,and which not only possessed well clinical effect,but also increased the quality of life.

Objective:To systematically review the efficacy and safety of acid-suppressive therapy including proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) and compare with those of placebo or blank control in the postoperative patients with stress ulcer bleeding (SUB) to provide evidence-based reference for clinical practice.Methods:The Cochrane library,Medline,Embase,CBM,CNKI,VIP,Wan Fang Data,clinicaltrials.gov,ISRCTN Register and WHO ICTRP were searched.Only randomized controlled trials (RCTs) of acid-suppressive therapy compared with placebo or blank control for postoperative stress ulcer bleeding were selected with bleeding rate,mortality,adverse drug reactions,gastric juice pH and length of stay as the indices.After the quality evaluation and data extraction,Meta-analysis was performed by using Stata12.0 statistics software.The results were expressed as relative risk(RR) and its corresponding 95% confidence interval(CI).Funnel plot and Eggers test were used to determine the publication bias;and then Grade approach was applied to assess the confidence in the evidence for each outcome.Results:Totally 15 trials enrolling 971 patients were selected,and acid-suppressive therapy was more effective than placebo or blank control in reducing the risk of stress ulcer bleeding,overt upper gastrointestinal bleeding and clinical important bleeding(RR 0.29,95% CI:0.19-0.45;RR 0.25,95%CI:0.10-0.64;RR 0.36,95%CI:0.17-0.77)(moderate),however,there was no statistical significance in the incidence of occult bleeding,mortality and adverse drug reactions (RR 0.79,95%CI:0.41-1.50;RR 0.49,95%CI:0.17-1.38;RR 0.78,95%CI:0.33-1.85,very low confidence).The subgroup analysis of drug classification,operation types and administration juncture showed that the incidence of SUB using PPI (RR=0.27) was lower than that using H2RA (RR=0.33);that of heart surgery (RR=0.20) was lower than that of general surgery (RR=0.31) and neurosurgery(RR=0.37);that of postoperative administration (RR=0.26) was lower than that of preoperative administration (RR=0.23).Conclusion:Acid-suppressive drugs seem to be more effective than placebo or blank control in reducing the risk of bleeding without significant increase of the risk of mortality or adverse drug reactions.The robustness of the conclusion is limited because of the low quality of the trial methodology,incomplete outcome indicators and lack of safety indices for pneumonia and clostridium diffcile-associated infection.Trials with high-quality and larger sample size are still needed to verify its clinical effects.

Objective To study the characteristics of the inpatients with cancer pain, the application of WHO three steps analgesic solution (three steps analgesic) and the application of traditional Chinese analgesic (TCM). Methods Retrospective investigation of distribution of cancer pain, situation of pain, application of TCM, and the application of conbination of three steps analgesic and TCM treatment, by using, clinical data from the oncology department of afflicated hospital of Liaoning university of TCM ranging from May, 2009 to June, 2010. Results 47.4% (517/1 090) of patiens were combined with cancer pain. Among the patients, majority were the middle-aged and old (59.19%) and male patients (57.63%). The abdominal pain (57.45%) and chest pain (37.91%) were topranks, and the distributions of pain period such assustainability (65.37%), moderately (53.38%), bloated pain (49.71%) and dull pain (29.98%) had larger proportion. The TCM excessive patterns(50.87%) were more than the TCM deficiency patterns (28.63%) or mixed TCM patters of excessive and deficiency patterns (20.50%). A total of 46 patients had mild pain, 76.09% of whom used TCM, 15.22% used first step drugs, and 8.69% used combination treatment, while 276 patients with moderate pain used second step analgesic, and 91.67%of them also used TCM, the rest195 patients with severe pain used third step analgesic, and 55.38%of them also used TCM. The time of pain release of TCM alone or combination of TCM and three steps analgesic were longer than the three steps analgesic alone. Conclusions Early intervention of traditional Chinese medicine on the patients with mild pain could reduce the dose of first step analgesic drugs, and TCM application at the second step could delay the speed of transtformfrom second to third step pain, and TCM could prevent the side effects of morphine when patients were with severe pain.