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 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.

End stage heart failure(ESHF) is the terminal stage of heart failure in patients with heart failure, or refractory heart failure. heart transplantation(HT) and mechanical circulatory assistance represented by ventricular assist device(VAD) are the main treatments for circulatory support in patients with ESHF. However, the serious shortage of donors has restricted the extensive development of HT. VAD technology, represented by left ventricular assist device(LVAD), has developed rapidly, and the 2-year survival rate after surgery has approached of HT. Although LVAD support can directly alleviate symptoms of left heart failure, it only partially relieves symptoms of right heart failure, resulting in high readmission rates.Therefore, more precise monitoring and regulation of right heart function in LVAD recipients is key to improving long-term prognosis. This article aims to provide an overview of strategies for the regulation of right heart function in patients after LVAD implantation.

For multi-center clinical research, how to ensure the quality of ethical review and improve the efficiency of ethical review through cooperation among centers is an important direction for clinical research management departments and research parties to explore. By combing and analyzing the existing pattern of multi-center ethical review at home and abroad, combining the current situation of the ethical review and management development in China, taking cancer clinical research as the breakthrough point, it was advocated to establish a cooperative review led by professional institute in domestic, on the basis of extensive and in-depth training exchanges and effective communication on the same platform, collaborative review, ensure quality and efficiency, so as to promote and implement the "mutual recognition" of ethical review. Then, this paper further put forward the concept of "whole-process linkage" in the ethical management process of multi-center clinical research, and pointed out that all research parties should clarify their responsibilities, enhance their awareness and ability, and jointly and comprehensively implement the protection of subjects among clinical researchers.

Objective To investigate the differences in clinical and radiographic features between severe influenza A H1N1 and H3N2 in children.Methods The clinical and radiographic data of children diagnosed with severe influenza A H1N1 and H3N2 were analyzed retrospectively.According to the pathogen subtypes,they were divided into H1N1 group(34 cases)and H3N2 group(23 cases).Differences in clinical data,laboratory results,treatment,hospitalization time,outcome,and radiographic features between the two groups were analyzed.The t-test was used for the comparison of normally distributed measurement data between the groups,and Mann-Whitney U test was used for the comparison of non-normally distributed measurement data between the groups.Chi-square test or Fisher's exact probability method was used for the analysis of counting data,depending on the situation.Results There were differences in the season of onset,clinical and radiographic features between the two groups.H1N1 subtype mostly occurred in win-ter,and mainly manifested as respiratory symptoms(wheezing/shortness of breath)and respiratory complications(severe pneumonia).H3N2 subtype was mainly observed in summer,and more likely to involve the central nervous system(CNS),presenting with neuro-logical symptoms(convulsions),abnormal electroencephalogram,and concurrent influenza associated encephalopathy(IAE).Conclusion There are significant differences in epidemiology,clinical and radiographic features between severe influenza A H1N1 and H3N2.H3N2 has a higher probability of concurrent IAE and should be highly vigilant in clinical practice.