Objective To optimize the formulation and preparation process of lenvatinib mixed micelles.Methods Hybrid micelles of lenvatinib were prepared by film hydration method,with Pluronic P123 and F127 as carrier materials.Optimal formulation was selected through single-factor experiments and central composite design-response surface methodology,and preliminary characterization of its physical properties was conducted.Results The optimized formulation and process conditions were identified as follows:P123 mass percentage of 80%,carrier material amount of 90 mg,drug loading of 10 mg,hydration volume of 6 ml,hydration time of 45 min,and rotary evaporation temperature of 55℃.The resulting lenvatinib mixed micelles had an average particle size of(104.0±0.32)nm,a polydispersity index(PDI)of 0.22±1.19,and a Zeta potential of(-2.56±0.81)mV.The average encapsulation efficiency was 83.33%±0.30%and the average drug loading was 8.67%±0.07%.The micelles displayed a uniform spherical morphology with a certain sustained-release capability.Conclusion The preparation process developed in this study was simple and feasible and produced drug-loaded micelles with high drug loading and encapsulation rates,and stable release,which could provide valuable insights for further research and development of lenvatinib mixed micelles.

Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.

BACKGROUND:Irreducible femoral neck fracture was difficult to obtain anatomic reduction.As a new type of internal fixation,the femoral neck system is still blank for the treatment of non-anatomical reduced femoral neck fractures. OBJECTIVE:To explore the biomechanical stability of femoral neck system internal fixation under nonanatomical reduction in the treatment of femoral neck fractures based on finite element analysis. METHODS:CT data of the hip joint of a healthy female adult were obtained.Anatomical reduction of femoral neck fracture models with Pauwels angles of 30°,50°,and 70° were established using Mimics 21.0,Geomagic Wrap 2021,and SolidWorks 2020.The fracture proximal ends of the three anatomical reduction models were shifted upward by 2 mm along the fracture line,and three positive buttress models with different Pauwels angles were obtained.In the same way,three negative buttress models were acquired by shifting downward by 2 mm.SolidWorks 2020 was used to make the femoral neck system internal fixation,and the nine femoral neck fracture models were assembled with the femoral neck system.Then Ansys 19.0 was used for finite element analysis.The displacement distribution and maximum displacement,stress distribution and maximum stress of the femur and femoral neck system were recorded under 2100 N stress. RESULTS AND CONCLUSION:(1)When Pauwels angles were 30°,50°,and 70°,the maximum stresses of the femoral neck system appeared to be concentrated at the junction of the sliding hip screw and anti-rotation screw.The maximum femur stresses appeared to be concentrated in the medial cortex of the femur.The maximum displacement was concentrated at the upper of the femoral head and femoral neck system.(2)When Pauwels angles were 30° and 50°,the maximum displacement and maximum stress of the femoral neck system and femur were:negative buttress>anatomical reduction>positive buttress.(3)When Pauwels angle was 70°,the maximum displacement and maximum stress of the femoral neck system were:negative buttress>anatomical reduction>positive buttress;the maximum displacement and maximum stress of the femur were:negative buttress>positive buttress>anatomical reduction.(4)With the increase of Pauwels angle,the biomechanical advantage of the positive buttress was weakening.However,it was better than a negative buttress.When Pauwels angle was 30°,positive buttress was more stable than anatomical reduction.When Pauwels angle was 50°,the biomechanical difference between positive buttress and anatomical reduction became smaller.When Pauwels angle was 70°,the stability of anatomical reduction was slightly better than positive buttress.(5)If it was difficult to achieve anatomical reduction of femoral neck fracture during operation,but the positive buttress had been displaced within 2 mm,the femoral neck system could be used to offer stable mechanical fixation.It is necessary to avoid negative buttress reduction.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To analyze the current status of salary system reform in public hospitals in Mianyang City, Sichuan Province, and provide reference for the deepening of salary system reform in public hospitals.Methods:From April to May 2023, a self-designed survey questionnaire was used to conduct a survey of medical staff in five municipal tertiary public hospitals through the Wenjuanxing platform. The survey questionnaire mainly included the basic information of the survey subjects, the implementation status of the salary system, and employee satisfaction with salary. In May 2023, semi-structured interviews were conducted with relevant personnel from government departments and public hospitals involved in the reform. The interview content included the reform measures taken and their impact, changes in medical staff salaries after the reform, and the current difficulties faced by the reform. Descriptive analysis was conducted on the data, and Chi-square test was used to compare the count data. Kendall′s tau-b test was used to analyze the correlation between salary level and basic information of the survey subjects.Results:In the reform of the salary system in public hospitals in Mianyang City, measures such as system construction, total salary quota determination and dynamic control, and salary management for non-establishment employees have been mainly adopted. 826 valid questionnaires were collected, with an effective response rate of 94.5%. The annual income level was positively correlated with age, education level, years of work experience, and professional title level ( r=0.420, P<0.001; r=0.245, P<0.001; r=0.364, P<0.001; r=0.504, P<0.001). Compared with the personnel in the same positions at the same level of hospitals in other cities and states in Sichuan Province, 274 people (33.2%) were quite satisfied or very satisfied with the current salary level; 350 people (42.3%) were quite satisfied or very satisfied with the salary distribution mechanism, and 441 people (53.4%) were quite satisfied or very satisfied with non-economic salaries. The proportion of survey respondents who believe that the existing salary structure and performance evaluation methods could reflect their actual work value was 464 people (56.2%) and 423 people (51.2%), respectively. A total of 10 people were interviewed, with 4 individuals believing that the salary level has increased after the reform, but the change was not significant compared to before the reform; 8 individuals believed that the current reform does not involve the reform of the salary structure; 6 individuals believed that the internal performance based salary distribution mechanism in hospitals was not sound; 3 individuals believed that there was insufficient attention to the reform of non-economic compensation; 7 individuals believe that the difficulties in the salary system reform were mainly concentrated on the unified understanding of policies, how to determine the increase in the total salary quota, and how to reasonably distribute it internally. Conclusions:Mianyang City has scientifically determined the total salary and implemented dynamic control, enhancing the public welfare nature of public hospitals, while also taking into account the salary management of employees both inside and outside the establishment, promoting equal pay for equal work. However, there were also issues such as disagreements on the dynamic adjustment of the total salary, an imperfect internal distribution mechanism within hospitals, and an incomplete salary system reform. It is necessary to further strengthen top-level design, reasonably increase salary levels, improve the internal distribution mechanism, and optimize the salary structure to continue deepening the reform of the salary system in public hospital.

Aim To explore the key targets of d-borneol combined with eisplatin for sensitization of cisplatin-resistant NCSLC cells by RNA-Seq and verify its mechanism. Methods Cisplatin-resistant human large cell lung cancer cells (H460/CDDP) were inoculated into the right armpit of male BALB/c nude mice (4 weeks old) to construct a xenograft tumor model. Then they were randomly divided into control group, vehicle group, eisplatin group, and combination group (d-borneol + eisplatin) with 6 nude mice and treated for 14 d. After last administration of 24 h, the tumor tissue was taken for RNA-Seq. And then real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to verify the expression of cell cycle-related molecules. Results RNA-seq analysis showed that there were significant differences in gene expression between the eisplatin group and combined group, and they were significantly enriched in cell cycle. RT-PCR and IHC results showed that d-borneol combined with eisplatin could significantly inhibit the expressions of cyclins (cyclin A2, cyclin D3) and cyclin-dependent kinases (CDK2, CDK6) and promote the expression of its upstream molecular cyclin-dependent kinase inhibitor CD-KI (P21, P27) (P<0. 05, P<0.01). Conclusions d-Borneol increases the sensitivity of eisplatin by increasing the expression of P21 and P27 and inhibiting the expression of cyclinA2/D3 and CDK2/6 to induce cell cycle arrest and inhibit the malignant proliferation of H460/CDDP cells, thereby achieving the effect of anti-drug sensitization.

In recent years, the prevalence of hyperglycemia has been increasing, and patients’ bodies have been seriously damaged. Compared with conventional Western drugs, natural products have fewer adverse reactions and delay the complications of hyperglycemia. As a valuable natural product resource, Small-leaf Kuding (SLK) contains various beneficial components for the human body. The aim of this study was to study the regulation effect of SLK extract at different doses on blood glucose metabolism in hyperglycemic mice. Lipopolysaccharide and streptozotocin were used to induce hyperglycemia in mice. Extract of SLK were administered intragastrically at low, medium, and high doses (5 g·kg

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Humans ; Isoniazid/pharmacology* ; Mycobacterium tuberculosis/genetics* ; Rifampin/pharmacology* ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Tuberculosis, Multidrug-Resistant/microbiology* ; Drug Resistance, Multiple, Bacterial/genetics* ; Bacterial Proteins/genetics*

ObjectiveTo understand the experience， knowledge and attitudes of e-cigarette users in Shanghai， and to provide evidence for the development of intervention programs for e-cigarette use. MethodsThe Respondent-Driven Sampling （RDS） method was used to recruit 40 e-cigarette users for qualitative interviews from November 2020 to February 2021. NVivo （11.0） software was used to code interview records， and the thematic pattern and relationship analysis were conducted. ResultsIn terms of the reasons and user experience of e-cigarette use， most respondents used e-cigarettes for the first time after recommendation of friends； The reasons for the current use of e-cigarettes focus on the subjective feelings generated by the use of e-cigarettes （easy to use， replacing traditional tobacco， and having many flavors）. Compared with traditional tobacco use， respondents said e-cigarettes tasted good and had no physical impact （they could be used all the time without making them uncomfortable）. In terms of the awareness of e-cigarette use related knowledge， the respondents' opinions on whether e-cigarettes caused health risks were mostly based on their own experience of using them， and they said it was difficult to identify real information online. As for whether they were interested in relevant knowledge， most respondents said they wanted to learn about the professional knowledge related to e-cigarettes. Regarding the attitude related to the use of e-cigarettes， most respondents believed that e-cigarettes are addictive， e-cigarettes are not a safe alternative to traditional tobacco， ande-cigarettes couldn't help them quit smoking. Three out of ten respondents said they supported including e-cigarettes in the Regulation on Smoking Control in Public. ConclusionThere are certain characteristics of e-cigarette users' feelings， related knowledge and attitude towards e-cigarette use that should be targeted to carry out publicity， education and intervention.