The advancement of artificial intelligence and big data has accelerated the exploration of decentralized clinical trials （DCTs）， and their future complementary relationship with traditional clinical trial models represents an inevitable trend. Given the greater complexity of preliminary research and protocol design in oncology drug clinical trials， the implementation of “decentralization” requires all stakeholders to clarify the responsibilities and authorities， enhance communication and collaboration， conduct comprehensive training， and progressively promote the integration and sharing of medical resources， thereby facilitating the establishment of a new quality and risk management framework. Concurrently， institutional review board should focus on reviewing and evaluating the scientificity， feasibility， and research risk controllability of DCT project protocol designs. It should also prioritize the implementation of informed consent norms， the management of safety event reporting and continuing review， and the protection of participants’ personal information and privacy. By adopting corresponding ethical review procedures， it emphasizes improving the risk identification and addressing capabilities of institutional review board members regarding the review projects， guiding researchers to adhere to DCT regulations. This aims to genuinely implement the “value-oriented， patient-centered” philosophy， thereby promoting the standardized and efficient conduct of DCTs.

Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

ObjectiveTo explore the central neuroregulation mechanism of heat-sensitive moxibustion for knee osteoarthritis on pain relief. MethodsThirty patients who did not have experience of Deqi （得气） during heat-sensitive moxibustion treatment were assigned to the "non-Deqi group"， while another 30 patients who had experience of Deqi were assigned to the "Deqi group". Both groups received moxibustion at the left Heding （EX-LE2） acupoint. In the Deqi group， after the patients experienced sensation of Deqi at the acupoint， moxibustion was applied at approximately 3 cm from the skin for 10 minutes； in the non-Deqi group， moxibustion was also applied at approximately 3 cm from the skin for 10 minutes. Both groups received treatment once daily for 10 consecutive days. Knee joint pain was assessed before and after treatment using the visual analog scale （VAS）. Resting-state functional magnetic resonance imaging （rs-fMRI） scans were performed on all participants before the first treatment session and after the final session on the 10th day. The fractional amplitude of low-frequency fluctuations （fALFF） maps before and after treatment were processed using the SPM12 module by MATLAB. ResultsAfter treatment， VAS scores in both groups were significantly lower than before treatment （P＜0.05 or P＜0.01）， with the Deqi group showing significantly lower VAS scores than the non-Deqi group （P＜0.01）. Compared to before treatment， the Deqi group exhibited significant activation in the prefrontal cortex （t = 6.28）， white matter （t = 6.36）， and left temporal lobe （t = 9.33）， while significant inhibition was observed in the occipital lobe （t = -9.86） and right cerebrum （t = -4.54， P＜0.01）； in the non-Deqi group， significant changes after treatment were observed in the left occipital lobe （t = -6.42）， left medial frontal gyrus （t = -4.35）， left middle frontal gyrus （t = -4.74）， right superior frontal gyrus （t = -4.82）， right superior temporal gyrus （t = -6.61）， and right cerebellar posterior lobe （t = -8.64）， all of which were in inhibited states （P＜0.01）. Compared to the non-Deqi group， the Deqi group exhibited significant activation after treatment in the external nucleus （t = 5.77）， white matter （t = 3.58）， right cerebrum （t = 5.84）， left cerebellum （t = 5.35）， and left cerebrum （t = 4.32）， while significant inhibition was observed in the prefrontal cortex （t = -4.16）， occipital lobe （t = -4.87）， and precentral gyrus （t = -4.46， P＜0.01）. ConclusionsHeat-sensitive moxibustion provides better analgesic effects for knee osteoarthritis under state of Deqi. Its central neuroregulation mechanism may be related to the involvement of the frontal lobe， temporal lobe， occipital lobe， external nucleus， white matter， right cerebrum， left cerebellum， left cerebrum， and precentral gyrus in modulating pain signals.

OBJECTIVE To investigate a suspected hospital-acquired infection cluster of Enterococcus faecium(Efm)in a neonatal intensive care unit(NICU)of the First Medical Center of Chinese PLA General Hospital,identify the source of infection and transmission routes,and provide a reference for precise prevention and control of hospital-acquired infections.METHODS Epidemiological investigations and environmental microbiological sam-pling were conducted for two neonates with Efm bloodstream infections in the NICU in Jul.2024 to detect Efm in the ward environment.Whole-genome average nucleotide identity(ANI)and multilocus sequence typing(MLST)were used to analyze the homology,drug resistance,and virulence factors of Efm isolates from patients and envi-ronments.Targeted intervention measures were proposed.RESULTS Two cases of Efm bloodstream infection were detected.A total of 37 environmental specimens were collected,and 2 were cultured Efm(the wipe dispenser o-pening and incubator handle of the patients).The drug susceptibility testing results of 2 environmental specimens were consistent with those of the two patient specimens.Genomic analysis confirmed high homology(ANI＞99.99％)among the four Efm isolates.After implementing a series of measures including centralized isolation,strict hand hygiene,thorough environmental cleaning and disinfection,strict disinfection and management of inva-sive devices,enhanced grouping of medical staff for diagnosis and treatment,the incident was effectively con-trolled.CONCLUSIONS This incident can be determined as cluster of hospital-acquired infection with Enterococcus faecium in the neonatal intensive care unit.The wet wipes are the source or transmission medium of contamina-tion.Inadequate disinfection of items and the environment,and insufficient hand hygiene of medical staff are the main reasons for this infection outbreak.Early identification of abnormal cluster of infection,investigation of the source of infection and transmission routes and timely implementation of targeted measures are the keys for preventing infection outbreaks.

OBJECTIVE By conducting evidence evaluation research on literatures,this study aims to reveal the o-verall characteristics and research hotspots in the field of combat trauma-related infections,ultimately providing data support for the prevention and control of such infections.METHODS Relevant research in this field was sys-tematically collected from open-source databases to construct a dataset.The overall characteristics,research hotspots,prevention and control strategies,and future challenges of trauma-related infections were summarized and analyzed.RESULTS From 2004 to 2024,184 papers were published.The United States contributed the most publications,with Uniformed Services University of the Health Sciences being the most productive research insti-tution and Professor Clinton K.Murray as the author with the highest number of publications.The top five key-words with the highest frequency were combat related injury,infection,Acinetobacter baumannii,epidemiology and management.Among the publicly published literature data on war trauma-related infections,blast injuries ac-counted for the largest proportion,mainly multi-site injuries,with limb injuries being the most common.Bacteri-al infections were more common than fungal infections,with gram-negative bacteria being predominant and A.baumannii being the most common.Besides early wound management and the use of antibacterial drugs,in-creased attention should be paid to infection prevention and control in austere environments and the development of novel countermeasures.These advancements are critical to address projected changes in combat trauma,inclu-ding increasingly complex injuries and substantially elevated risks of infection and antimicrobial resistance.CONCLUSION This study systematically presents research hotspots,developmental trends,and prospects in com-bat trauma-related infections through evidence evaluation study,providing novel perspectives for researchers and facilitating further development in this field.

Objective To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule,ophiopogonin,on enhancing the immune response of a subunit vaccine with the receptor-binding domain(RBD)of coronavirus spike protein as the antigen.Methods CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D'(OPD')on bone marrow-derived dendritic cells(BMDCs).Female Balb/c mice were randomly divided into RBD,RBD/OPD',RBD/Alum,and control groups.The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse,and immunization was carried out according to the intramuscular injection immunization procedure on days 0,21,and 42.The titers of specific IgG and its subtype antibodies were detected by ELISA.The cytokine levels in the supernatant of splenocytes were detected using ELISA.The number of splenocytes secreting IFN-γ was detected by ELISpot.Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs.The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry.The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.Results When the concentration of OPD'was less than 5 μg/mL,the survival rate of BMDCs was 100%.After a single intramuscular injection in mice,except for a slight decrease in body weight,the other biochemical indicators were within corresponding normal ranges.After intramuscular injection immunization of the vaccine,the titers of serum-specific IgG,IgG1,and IgG2a in the RBD/OPD'group were significantly higher than those in the RBD group(P<0.05).Compared with the RBD group,the RBD/OPD'group induced a high-level Th1 cell immune response of IL-1β,TNF-α,and IFN-γ(P<0.01)and had more lymphocytes secreting IFN-γ(P<0.001).Laser confocal microscopy displayed that BMDCs took up more antigens after OPD'treatment,which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate(P<0.01).Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD'group than the RBD group,suggesting that OPD'may activate the PPAR signaling pathway to exert its adjuvant effect.Conclusion OPD'effectively enhances the immune response of the RBD subunit vaccine,and its action mechanism may be related to the activation of the PPAR signaling pathway.

Objective To establish a mouse model of infection with the minimum lethal dose of Vibrio vulnificus(V.vulnificus)and to evaluate the protective efficacy of inactivated whole-cell(IWC)vaccine using this model.Methods A mouse model of lethal-dose infection was established by intraperitoneal injection of different doses of V.vulnificus.Bacterial colonization in the organs was detected with tissue homogenate plating,and pathological changes in the organs were observed after tissue section staining.Flow cytometry was used to detect immune cell responses after liver tissues were digested into single-cell suspension.IWC vaccine of V.vulnificus was prepared,and the mice were immunized through different routes to observe the protective efficacy of the vaccine.Results A mouse model of infection with the minimum lethal dose at 1×106 CFU of V.vulnificus was successfully established.After infection,the bacteria were mainly colonized in the liver of mice and caused severe pathological damages.Compared with the uninfected mice,the proportion of neutrophils in the liver was significantly increased in the infected mice,whereas the proportions of B cells and T cells were correspondingly decreased(P<0.05).A single intramuscular or intraperitoneal injection of the IWC vaccine could protect the mice effectively against lethal infection of V.vulnificus in 7 d later(P<0.01),although the level of serum IgG having no significant increase.Conclusion A mouse model of lethal-dose infection with V.vulnificus is successfully established,with histopathological characteristics.The IWC vaccine of V.vulnificus rapidly mediates immune protection in this model probably independent of IgG.

Objective To prepare tubeimoside Ⅲ nanoemulsion(TBMⅢ-NE)and evaluate its adjuvant effect in vaccines.Methods TBMⅢ-NE was prepared using low-energy emulsification.Dynamic light scattering was used to characterize the particle size and polydispersity index of the obtained TBMⅢ-NE,and transmission electron microscopy(TEM)was employed to observe the morphology.CCK-8 assay was utilized to determine the cytotoxicity of TBMⅢ-NE on bone marrow-derived dendritic cells(BMDCs).The in vitro safety of TBMⅢ-NE was evaluated using a hemolysis assay.The ability of TBMⅢ-NE to promote the phagocytosis of antigens by DC2.4 cells was observed using confocal laser microscopy.After co-incubation of TBMⅢ-NE with BMDCs,the expression levels of CD40,CD86,MHC-Ⅰ,and CCR7 on the surface of BMDCs were detected using flow cytometry,and the levels of cytokines in the supernatant of BMDCs were measured using enzyme-linked immunosorbent assay(ELISA).After female BALB/c mice were immunized with the SARS-CoV-2 antigen RBD in combination with TBMⅢ-NE,ELISA was conducted to determine the serum levels of specific IgG,IgG2a,and IgG1 antibodies.The number of specific IFN-γ-secreting cells in mouse splenocytes was detected using enzyme-linked immunospot(ELISpot)assay.Results The prepared blank nanoemulsion(BNE)and TBMⅢ-NE were in a particle size of 25.46 and 25.89 nm,and a polydispersity index of 0.214 and 0.125,respectively.TEM displayed that TBMⅢ-NE was in uniform sphere and well dispersed.When the TBMⅢ-NE adjuvant was diluted by 400-fold,the survival rate of BMDCs was approximately 86%.Compared with free TBMⅢ,the hemolytic toxicity of TBMⅢ-NE was significantly reduced(P<0.01).TBMⅢ-NE promoted the phagocytosis of antigens by DC2.4 cells and significantly increased the expression of CCR7 on the surface of BMDCs(P<0.05),indicating its potential to promote more dendritic cells to effectively migrate to lymph nodes.TBMⅢ-NE also promoted the expression of IL-6 and IL-1β in the supernatant of BMDCs(P<0.05).When combined with RBD,TBMⅢ-NE significantly increased the levels of specific IgG,IgG2a,and IgG1 antibodies in mouse serum(P<0.01)and promoted the secretion of specific IFN-γ in splenocytes(P<0.01),indicating that TBM Ⅲ-NE could enhance specific cellular immune responses.Conclusion A stable and highly effective TBMⅢ-NE that can induce humoral and cellular immune responses is successfully prepared.

Objective:To explore the therapeutic effect of compound Kuijie Ankang Decoction on ulcerative colitis (UC) model mice by non targeted metabonomics; To explore its mechanism.Compound Kuijie Ankang.Methods:The mice were randomly divided into blank control group, model group, Kuijie Ankang Decoction group and sulfasalazine group, with 12 mice in each group. Except the blank control group, the other groups were given 1.5% DSS solution for free drinking to prepare UC model. After successful modeling, Kuijie Ankang Decoction group was intragastrically administered with compound Kuijie Ankang Decoction of 9.68 g/kg, sulfasalazine group was intragastrically administered with sulfasalazine capsule suspension of 320 mg/kg, model group and blank control group were intragastrically administered with equal volume of purified water, once a day, for 7 consecutive days. The body mass and disease activity index (DAI) score of mice were measured. ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the colon tissue of mice; the protein expressions of Claudin-1 and Zo-1 in colon tissue were detected by immunofluorescence method. HE staining was used to observe the pathological changes in the colon, and UHPLC-OE-MS technology was used to analyze the endogenous metabolite structure of mouse colon tissue, differential metabolites and related metabolic pathways were screened.Results:Compared with the model group, the colon length in Kuijie Ankang Decoction group and sulfasalazine group increased ( P<0.01), the DAI score decreased ( P<0.01), the levels of TNF-α, IL-1β and IL-6 in colon tissue decreased ( P<0.01), the level of IL-10 increased ( P<0.01), and the average optical density of Claudin-1 and Zo-1 protein increased ( P<0.01 or P<0.05). Metabolomics analysis identified 26 potential differential metabolites, including nicotinamide adenine dinucleotide, guanine, gamma aminobutyric acid, and thiamine, affecting 26 key metabolic pathways, including lysine biosynthesis, thiamine metabolism, cysteine and methionine metabolism. Conclusion:Kuaijie Ankang Decoction may improve metabolites such as Gamma aminobutyric acid and thiamine through metabolic pathways such as lysine biosynthesis to alleviate inflammatory reactions, thereby exerting therapeutic effects on ulcerative colitis in mice.

Objective To discuss the short-term efficacy of endovascular recanalization for symptomatic non-acute internal carotid artery occlusion.Methods A total of 90 patients with symptomatic non-acute internal carotid artery occlusion,who were admitted to the Department of Neurology of Tianjin Municipal Teda Hospital of China from August 2017 to December 2021,were selected as the research objects.The patients were divided into study group(n=45)and control group(n=45).Percutaneous endovascular recanalization of internal carotid artery occlusion was performed for the patients of the study group,and standardized antiplatelet aggregation and anti-lipid therapy(including oral aspirin,clopidogrel bisulphate and atorvastatin)was adopted for the patients of the control group.The symptom recurrence rate at one year after treatment in both groups was analyzed.Results Of the 45 patients in the control group,4 were lost in touch,and 41 completed the one-year follow-up.Of the 45 patients in the study group,2 patients had failure of surgery,one patient had lost contact visit,and 42 completed the one-year follow-up.Postoperative intracranial hemorrhage occurred in 2 patients.After one year of follow-up,in the control group 26 patients(63.41％)developed recurrence of symptoms,presenting as transient ischemic attack(TIA,n=13,31.7％)and cerebral infarction(n=13,31.7％),and in the study group 8 patients(4.76％)developed recurrence of symptoms,presenting as TIA(n=6,14.3％)and cerebral infarction(n=2,4.8％);the incidence of cerebral infarction in the study group was strikingly lower than that in the control group,and the difference between the two groups was statistically significant(P＜0.05).In the patients with grade Ⅲ compensation,the recurrence rate of symptoms was remarkably decreased after endovascular recanalization of internal carotid artery occlusion,and the difference between the two groups was statistically significant(P＜0.05).However,in the patients with grade Ⅰ or grade Ⅱ compensation,although the recurrence rate of symptoms was decreased after endovascular recanalization of internal carotid artery occlusion,the difference between the two groups was not statistically significant(P＞0.05).Conclusion For the treatment of patients with symptomatic non-acute internal carotid artery occlusion,percutaneous endovascular recanalization of internal carotid artery occlusion is clinically safe,it can significantly decrease the recurrence rate of symptoms.