OBJECTIVE To analyze the current status and challenges in importing rare disease drugs in China， providing references for optimizing the import process and improving relevant policies. METHODS Questionnaires and interviews were conducted with stakeholders involved in rare disease drug importation， including government departments， multinational pharmaceutical enterprises， healthcare institutions， and patient organizations. This explored the current situation and challenges encountered by each party. Expert opinions were synthesized to propose improvement suggestions. RESULTS A questionnaire survey of representatives from 25 multinational pharmaceutical companies in the rare disease field revealed that these companies had a strong willingness to import rare disease drugs， with 58.33% of them practicing diverse import models. However， significant challenges hindered this process， including unclear regulations （54.17%）， complex approval procedures （45.83%）， and excessively long approval cycles （41.67%）， negatively impacting their motivation. Meanwhile， interviews with 13 experts from government departments， healthcare institutions， pharmaceutical enterprises， and patient organizations identified deficiencies in policy design， approval processes， sampling inspection costs， and communication efficiency with regulators. Additionally， the drug import model in special medical zones also required improvement. CONCLUSIONS The importation of rare disease drugs in China faces challenges such as incomplete policies， inflexible regulatory mechanisms， and insufficient communication channels. It is recommended to enhance the rare disease definition criteria， optimize import incentive policies， and refine regulatory models， so as to further optimize the import process of rare disease drugs and improve relevant policies.

Objective: To investigate the incidence trend and epidemic characteristics of notifiable infectious diseases in Nanjing City from 2004 to 2022, so as to provide the basis for improving the prevention, control, and monitoring strategies of infectious diseases. Methods: Data pertaining to notifiable infectious diseases reported in Nanjing City from 2004 to 2022 were retrieved from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. Infectious diseases were classified by law and transmission routes. Temporal distribution incidence of notifiable infectious diseases were descriptively analyzed. The trends in incidence of notifiable disease were analyzed using annual percent change (APC) and average annual percent change (AAPC). Results: A total of 33 types of notifiable infectious diseases with 505 275 cases were reported in Nanjing City from 2004 to 2022. The average annual reported incidence was 347.45/105, showing a decreasing trend from 2018 to 2022 (APC=-13.499%, P<0.05), and there was no significant trend overall (AAPC=-1.586%, P>0.05). A total of 203 235 cases of 25 types of class A and B notifiable infectious diseases were reported, with an average annual reported incidence of 139.75/100 000, showing an overall decreasing trend (AAPC=-4.954%, P<0.05). Eight types of class C notifiable infectious diseases with 302 042 cases were reported, with an average annual reported incidence of 207.69/100 000. The reported incidence showed an increasing trend from 2004 to 2018 (APC=10.117%, P<0.05), and a decreasing trend from 2018 to 2022 (APC=-27.467%, P<0.05). There was no trend overall (AAPC=-0.360%, P>0.05). The reported incidence of blood-borne and sexually transmitted infectious diseases was the highest in class A and B infectious diseases, with an average annual reported incidence of 69.88/100 000, which was at a high epidemic level throughout the year, except February. The reported incidence of respiratory infectious diseases was 51.30/100 000, with a high reported incidence in April and December. The reported incidence of intestinal infectious diseases was the highest (178.06/100 000) in class C infectious diseases, with a high reported incidence in June and November. Conclusions The reported incidence of notifiable infectious diseases in Nanjing City was generally stable from 2004 to 2022. The peak incidence of respiratory infectious diseases occurred in winter and spring, and that of intestinal infectious diseases was in summer and autumn. It is necessary to strengthen the surveillance and intervention of blood-borne and sexually transmitted infectious diseases, respiratory infectious diseases, and intestinal infectious diseases to reduce the risk of infectious diseases.

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

Objective:To investigate the effect of sleep on physical performance and the correlation between sleep quality and physical performance in the elderly.Methods:In this prospective multicenter case-control study, 472 elderly people aged 60-80 years were recruited from three regions in China, Beijing, Tianjin, and Hainan Province.Basic information of study participants was collected through face-to-face interviews, and physical performance of study participants was assessed by the time up and go(TUG)test on site, with 106 cases(22.5%)in the normal physical performance group and 366 cases(77.5%)in the abnormal group.The Pittsburgh Sleep Quality Index(PSQI)and the Epworth Sleepiness Scale(ESS)were applied to assess sleep quality of study subjects.Correlation analysis was performed to examine factors affecting subjects' physical performance.Results:Age, history of alcohol consumption, BMI, past medical history, the ESS score, daytime sleepiness, and some components of PSQI, such as sleep quality, sleep efficiency, sleep disturbances, use of sleeping drugs and daytime dysfunction, were influencing factors of the TUG score.Two components of PSQI, sleep duration and habitual sleep efficiency, and the ESS score were positively correlated with physical performance.Logistic regression analysis showed that risk factors for decreased physical performance in the elderly included increased age( OR=1.125, 95% CI: 1.083-1.168, P<0.01), history of alcohol consumption( OR=0.482, 95% CI: 0.384-0.605, P<0.001), abnormally high body mass index( OR=1.663, 95% CI: 1.340-2.063, P<0.01), hyperlipemia( OR=0.156, 95% CI: 0.077-0.318, P<0.01), digestive system diseases( OR=0.154, 95% CI: 0.044-0.532, P<0.01), use of sleeping drugs( OR=0.415, 95% CI: 0.202-0.854, P<0.05), daytime sleepiness( OR=4.234, 95% CI: 2.800-6.403, P<0.01), a high habitual sleep efficiency score of PSQI( OR=1.425, 95% CI: 1.214-1.672, P<0.01)and a high sleep disturbances score in PSQI( OR=3.356, 95% CI: 2.337-4.819, P<0.01). Conclusions:The incidence of physical performance decline is high in the elderly.There is a correlation between physical performance and sleep quality.

Objective To analyze the clinical manifestations of delayed serological transfusion reactions(DSTR)after platelet transfusion in tumor patients,and to explore the transfusion strategy.Methods Clinical data and laboratory test re-sults of patients with positive antibody screening were analyzed after platelet transfusion in our hospital from January 1,2015 to June 30,2023,and the incidence rate,clinical characteristics and transfusion strategy of patients with DSTR were ana-lyzed.Results A total of 2 553 patients with 6 057 platelet transfusions were reviewed.Eight patients developed DSTR and received a total of 21 therapeutic amounts of platelets,and 5 patients were subsequently transfused with red blood cells.Rh system antibodies were detected in 7 cases(4 anti-E,1 anti-c/E,1 anti-C and 1 anti-c)and Kell system antibodies in 1 case.Conclusion Tumor patients may also develop DSTR after platelet transfusion.It is necessary to pay close attention to the antibody situation and perform matched transfusion when transfusing blood again.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal–fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal–fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal–fetal tolerance based on maternal–fetal crosstalk. Insights into maternal–fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Objective To investigate the research status and the research hotspots on male nurses at home and abroad in last decade,so as to provide references for further research in male nurses.Methods Literature between 2013 and 2024 on male nurses were retrieved from the Web of Science(WOS)and CNKI.CiteSpace 6.2.6 R7 software was used to analyse the volume of publication,keyword co-occurrence,keyword clustering and emergence.Results A total of 736 articles were included in the study.From 2013 to 2023,the number of published papers of male nurses in CNKI and WOS showed an increasing trend.The research was primarily affiliated with 263 institutions across 62 countries.The country with the highest volume of publication is China,followed by the United States,although there was a need to enhance collaboration with other nations.The institution with the most publications is the Hong Kong Polytechnic University.A comprehensive analysis of keyword co-occurrence,clustering,and emerging trends revealed that the research hotspots in the field of male nursing in CNKI mainly includes the advantages of male nurses,psychological capital,humanistic care,development,needs,professional identification.Whereas WOS focuses on the topics such as gender bias against male nurses,mental health,workplace violence,ambivalent sexism,motivational barriers,individual differences,societal prejudice and knowledge and attitucle.Both domestic and international research on male nurses primarily consist of cross-sectional surveys and qualitative studies,with fewer intervention studies.Currently,the researches regarding male nursing focus on the qualitative study of mental health of male nurses.Conclusion Focusing on the mental health and professional status of male nurses,domestic scholars need to increase the formulation and implementation of interventions in this field in order to address the practical issues faced by male nurses,therefore to promote the comprehensive development of the nursing profession,enhance the overall quality and service quality of the nursing team,and provide patients with higher quality in nursing services.

Objective:To explore the effectiveness of intelligent multifunctional rehabilitation instrument for lower limb diseases in preventing deep vein thrombosis in stroke patients with hemiplegia.Methods:From September 2022 to September 2023, convenience sampling was used to select 121 stroke patients with hemiplegia admitted to the Department of Neurology, Neurosurgery, and Rehabilitation of Cangzhou Central Hospital as the study subject. The study subjects were divided into a control group ( n=58) and an observation group ( n=63) using the random number table method. The control group was treated with standard medication and routine rehabilitation nursing, while the observation group was treated with the intelligent multifunctional rehabilitation instrument for lower limb diseases on the basis of the control group. The intervention time was four weeks for both groups. This study compared the incidence of clinical symptoms of lower limbs (swelling, pain, skin temperature, gastrocnemius test results) and deep vein thrombosis in the lower limbs between two groups of patients after intervention. The plasma D-dimer levels, femoral vein blood flow velocity, and blood flow of the two groups of patients before and after intervention were also compared. Results:After intervention, the number of cases of lower limb clinical symptoms (swelling, pain, elevated skin temperature, positive results of gastrocnemius muscle test) and deep vein thrombosis in the observation group was lower than that in the control group ( P<0.05). In the observation group, the plasma D-dimer levels of patients were lower than those of the control group ( P<0.05), and the femoral vein blood flow velocity and blood flow were higher than those of the control group ( P<0.05) . Conclusions:The intelligent multifunctional rehabilitation instrument for lower limb diseases can effectively prevent the occurrence of deep vein thrombosis in stroke patients with hemiplegia.

Objective:To investigate the effects and mechanisms of exogenous calcium-binding protein S100A4 on prolifera-tion,survival and migration functions of glioma cells.Methods:Pan-cancer dataset was downloaded from UCSC database for the analysis of S100A4 expression and prognosis in pan-cancer,and transcriptome and clinical data of glioma patients were downloaded from CGGA database.Prognosis and progression of S100A4 expression in glioma patients were analyzed by R software.S100A4 protein network interaction of glioma patients were addressed by online analytical tools GEPIA and STRING.Human glioma cell lines(U87 and U251)were cultured in vitro,and the experiment was divided into 3 groups:PBS group,S100A4 group and S100A4+TAK242 group[Resa-torvid(TAK242)was a specific inhibitor of Toll-like receptors 4(TLR4)].Flow cytometry was used to detect proliferation and apopto-sis of glioma cells.Wound healing assay,Transwell assay and clone formation assay were used to detect migration and proliferation ability of U87 and U251 cells,and Western blot was used to detect levels of TLR4 protein and NF-κB related signaling proteins.Results:Bioinformatics results showed that S100A4 was significantly upregulated in multiple tumours(P<0.05),which included glio-blastoma(GBM),lower grade glioma(LGG),stomach adenocarcinoma(STAD),liver hepatocellular carcinoma(LIHC),etc,with poorer prognosis in GBM and LGG.Compared with glioma patients with low expression of S1004,high expression S100A4 in glioma patients had shorter survival and higher degree of WHO classification.In addition,S100A4 protein in glioma patients may interact with Annexin A2(ANXA2),TLR4 and advanced glycosylation end product-specific receptor(AGER)proteins.In cellular experiments,U87 and U251 cells showed enhanced proliferation and migration,and significantly up-regulated levels of TLR4,p-ERK1/2,p-p38 and p-p65 proteins after exogenous S100A4 treatment compared to PBS group(P<0.05),while glioma cells in S100A4+TAK242 group showed weaker proliferation and migration,and lower TLR4,p-p38 and p-p65 protein levels than those in S100A4 group,TLR4,p-ERK1/2,p-p38,p-p65 protein levels were significantly down-regulated(P<0.05).Conclusion:S100A4 may regulate func-tion of glioma proliferation,migration and survival through TLR4/NF-κB signaling pathway.