Objective To understand the facilitating and obstacle factors for pediatric nurses in implementing interventions for children's medical fears and to provide a foundation for exploring intervention strategies for pediatric nurses to effectively tackle children's medical fears.Methods By purposive sampling,face-to-face interviews were conducted with 20 pediatric nurses in a tertiary-level A children's hospital in Wenzhou City from December 2023 to February 2024.Traditional content analysis was used for data analysis.Results Facilitators and obstacle factors to the implementation of medical fear interventions by pediatric nurses were extracted.The 4 sub-themes of the facilitator theme include awareness of the importance of medical fear intervention,the drive of individual empathy,positive peer support,and the construction of a suitable hospital environment.The 3 sub-themes of the obstacle theme include the lack of individualized intervention skills for medical fear,heavy workload,interference from negative emotional behavior of family members.Conclusion There are many factors influencing paediatric nurses to implement medical fear interventions for children.It is recommended that clinical nursing administrators should strengthen the systematic training of pediatric nurses'knowledge about medical fear interventions for children,unite with multidisciplinary experts,and recruit medical social workers or volunteers to collaborate with nurses and children's families to cope with children's medical fears together and to promote physical and mental health of hospitalized children.

Objective To understand the facilitating and obstacle factors for pediatric nurses in implementing interventions for children's medical fears and to provide a foundation for exploring intervention strategies for pediatric nurses to effectively tackle children's medical fears.Methods By purposive sampling,face-to-face interviews were conducted with 20 pediatric nurses in a tertiary-level A children's hospital in Wenzhou City from December 2023 to February 2024.Traditional content analysis was used for data analysis.Results Facilitators and obstacle factors to the implementation of medical fear interventions by pediatric nurses were extracted.The 4 sub-themes of the facilitator theme include awareness of the importance of medical fear intervention,the drive of individual empathy,positive peer support,and the construction of a suitable hospital environment.The 3 sub-themes of the obstacle theme include the lack of individualized intervention skills for medical fear,heavy workload,interference from negative emotional behavior of family members.Conclusion There are many factors influencing paediatric nurses to implement medical fear interventions for children.It is recommended that clinical nursing administrators should strengthen the systematic training of pediatric nurses'knowledge about medical fear interventions for children,unite with multidisciplinary experts,and recruit medical social workers or volunteers to collaborate with nurses and children's families to cope with children's medical fears together and to promote physical and mental health of hospitalized children.

Objective To explore the relationship between basic motor skills and social interaction ability in school-age children with moderate autism,and the mediating role of executive function and the realization path.Methods A cross-sectional design was used to investigate 117 school-age children with autism from Sep.to Dec.2020.The level of basic motor skills was assessed by the test of gross motor development(TGMD),the impairment of executive function was assessed by the behavior rating inventory of executive function(BRIEF),and the social disorder was assessed by the social responsive scale-second edition(SRS-2).Pearson correlation analysis was used to explore the interrelationship,and structural equation modeling was applied to explore the path relationship.Results There was a significant negative correlation between the level of basic motor skills and SRS-2 scores(r=-0.312,P＜0.001).There were significant negative correlations between the level of basic motor skills and the BRIEF scores of inhibition(r=-0.336,P＜0.001),switching(r=-0.325,P＜0.001),affective control(r=-0.338,P＜0.001),task initiation(r=-0.240,P=0.009),working memory(r=-0.278,P=0.002),and planning(r=-0.224,P=0.015).The SRS-2 score was positively correlated with the BRIEF scores of inhibition(r=0.378,P＜0.001),switching(r=0.299,P=0.001),affective control(r=0.417,P＜0.001),task initiation(r=0.246,P=0.007),working memory(r=0.409,P＜0.001),and monitoring(r=0.258,P=0.005).Executive function played a complete intermediary role between basic motor skills and social interaction ability(B=-1.912,95％confidence interval:-3.116 to-1.069).Conclusion In school-age children with moderate autism,executive function and social interaction ability change positively with the level of basic motor skills.Basic motor skills can affect social interaction ability through the mediating role of executive function,and inhibition and affective control are important pathways to achieve this.

OBJECTIVE To provide a reference for the safe use of drugs in patients with complex venous thromboembolism （VTE） and acute renal insufficiency. METHODS Clinical pharmacists participated in the management of anticoagulant therapy for a patient with complex VTE complicated with acute renal insufficiency， and evaluated the patient as high-risk thrombosis and bleeding based on their medical history， laboratory test results， etc.； combined with the complexity of thrombosis and renal insufficiency， clinical pharmacists suggested that enoxaparin sodium should be used in the acute stage of thrombosis （5 to 21 days after onset）， and then warfarin should be adopted for oral anticoagulation treatment. Because the patient’s anticoagulation was not up to the standard （the target range of the international normalized ratio was 2-3）， clinical pharmacists suggested increasing the warfarin dose， detecting the warfarin metabolism genotype， and adjusting the warfarin dose according to the genotype； at the same time， clinical pharmacists developed an anticoagulation monitoring plan to ensure the safety of anticoagulation treatment. RESULTS Doctors had adopted all the recommendations of clinical pharmacists. The patient did not experience adverse events such as bleeding or worsening of thromboembolism during anticoagulation in the hospital. When the anticoagulation met the standards， the patient was allowed to be discharged with medication. CONCLUSIONS By participating in the anticoagulation treatment management of patients with complex VTE and acute renal insufficiency， clinical pharmacists have assisted doctors in formulating personalized anticoagulation plans to promote the compliance with the anticoagulation treatment standard and ensure the safety and effectiveness of medication for patients.

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

Objective:To investigate the treatment options for multiple myeloma patients with central nervous system involvement (CNS-MM) , as well as their clinical characteristics and prognostic factors.Methods:Between January 2011 and January 2022 our center diagnosed 18 people with CNS-MM. A retrospective analysis was done on the clinical information from the initial diagnosis and central nervous system involvement, and it was compared to 1∶3 matched newly diagnosed MM from the same period. Analysis was done on the clinical characteristics and survival rates of the two groups.Results:In patients with CNS-MM, the median time of onset was 14.2 (0.9-79.6) months and the median overall survival (OS) was 30.5 months from initial diagnosis and only 3.8 months in patients after CNS involvement. The CNS-MM patients showed more IgD type ( P=0.010) , severer anemia ( P=0.014) , a higher proportion of bone marrow plasma cells ( P=0.013) , more extramedullary lesions ( P=0.001) , and increased lactic dehydrogenase (LDH) ( P=0.009) when compared to the control group. Lenalidomide or pomalidomide-based combinations had higher rates of hematology and CNS remission than bortezomib or daratumumab-based regimens (75.0% vs 16.7% , P=0.019) . Patients who received IMiD-based regimens and had 2 high-risk factors at initial diagnosis (high LDH and extramedullary lesions) had a significantly lower incidence of CNS-MM ( P=0.026) . At the initial diagnosis, LDH ( P=0.008, HR=7.319, 95% CI 1.663-32.219) and extramedullary lesions ( P=0.006, HR=8.054, 95% CI 1.828-35.486) were independent risk factors for the occurrence of CNS-MM. Conclusion:Patients with CNS-MM had a poor prognosis. Patients with high LDH or extramedullary lesions at the time of the initial diagnosis are more likely to have CNS-MM. The prognosis of this patient may be improved by immunoregulator-based therapy.

Objective:Through the analysis of intelligent nursing patents, to provide reference for clinical nurses to understand the development trend of intelligent nursing patents and carry out related inventions.Methods:The website of China Intellectual Property Office and CNKI were searched with the keywords of " intelligence" , " intellectualization" and " artificial intelligence" , " nursing" and " nurse" from the establishment of the database to December 31, 2020. Information of the patent application time, application area, patent type, main classification number and other patent information were analyzed.Results:Until 2020, China applied for 4 128 patents related to intelligent nursing, among which invention patents were the most, and appearance patents were the least; before 2006, intelligent nursing patents were in the early stage of development, from 2006 to 2014, it showed a slow increasing trend, since 2015, it entered the stage of rapid growth; the regions with the largest number of applications were Shandong, Jiangsu, Guangdong, Shanghai and Zhejiang; IPC of A61, G06, H04, G16 and A47 accounted for the largest proportion, and showing an upward trend as a whole, but different technical fields show different growth rates; intelligent nursing was the most popular. The number of applications for beds and related ancillary products was the largest, followed by intelligent nursing monitoring equipment.Conclusions:It is suggested that to improve the patent incentive mechanisms, encourage nurses to solve clinical problems from an intelligent perspective, and actively promote the transformation of intelligent nursing patents.

Objective:To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM) .Methods:The clinical characteristics, adverse reactions, efficacy, and prognosis of 46 patients with RRMM treated with daratumumab in Shanghai Changzheng Hospital from September 2017 to March 2020 were retrospectively analyzed.Results:All patients were treated with daratumumab-based regimen: 8 in the Dd group, 35 in the DRd group, and 3 in the DVd group. With a median follow-up of 9.6 months, the overall response rate (ORR) was 75% [complete remission (CR) rate 18.2% ] among the 44 patients available for evaluation. The ORRs of patients resistant to bortezomib, lenalidomide, and both were 70.6% , 69.2% , and 63.6% , respectively. The CR rates of patients resistant to bortezomib, lenalidomide, and both were 17.6% , 11.5% , and 13.6% , respectively. No significant difference was observed in ORR and CR rates among the three groups. The ORRs of the DRd, DVd, and Dd groups were 85.3% , 66.7% , and 28.6% , respectively ( P=0.007) . The median PFS of 46 patients was 8.9 months, the median OS was not reached, and the 1-year OS rate was 74% . The median PFS and OS in the DRd group were longer than those in the Dd group (PFS: 14.4 months vs 2.0 months; OS: not reached vs 5.2 months) . After treatment with daratumumab, neutropenia is the most common hematological adverse reaction above grade 3. Non-hematological adverse reactions are mainly infusion-related adverse reactions and infections. Prognostic analysis showed that patients with extramedullary invasion had shorter PFS and OS compard with patients without extramedullary invasion (PFS: 5.7 vs 14.4 months, P=0.033; OS: 6.3 months vs not reached, P=0.029) . The OS of patients with an ECOG score of 3-4 was significantly shorter than patients with an ECOG score of 1-2 (5.9 months vs not reached, P=0.004) . Conclusion:Daratumumab-based regimens have good efficacy and safety in the treatment of RRMM.

Objective: To investigate the effects of sinomenine on brain edema and the expression of aquaporin 4 (AQP-4) and aquaporin 5 (AQP-5) in rats with acute brain injury. Methods: According to random number table method, rats were divided into sham operation group, model group, low-dose sinomenine group, high-dose sinomenine group, 20 in each group. In addition to the sham operation group, the rat brain injury model was established by Feeney free falling impact method. Rats in low and high dose of sinomenine group were given sinomenine 30, 60 mg/kg by intraperitoneal injection, and the sham operation group and model group were injected intraperitoneally with the same volume of normal saline, once per day for 7 days. Histopathological changes in each group were observed by HE staining and electron microscope. Western blot and RT-PCR were used to detect AQP-4 and AQP-5 protein and gene expression in brain tissue. Results: The pathological results showed that the nerve cells in the model group were loosely arranged, disordered in hierarchy, some cells appear to have degenerated. The degeneration and necrosis of nerve cells in the low and high dose sinomenine group were less than those in the model group. Compared to the model group, the expression of AQP-4 (0.74 ± 0.13, 0.49 ± 0.11 vs. 1.30 ± 0.21), AQP-5 (0.98 ± 0.07, 0.45 ± 0.10 vs. 1.47 ± 0.18) in the low dose and high dose sinomenine group significantly decreased (P<0.05). The expression of AQP-4 (1.48 ± 0.18, 1.26 ± 0.12 vs. 2.04 ± 0.14), AQP-5 (1.31 ± 0.17, 1.20 ± 0.11 vs. 1.87 ± 0.15) mRNA in the low dose and high dose sinomenine group significantly decreased (P<0.05). Conclusions Sinomenine could alleviate cerebral injury by lowering the expression of AQP-4 and AQP-5.