Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objective To analyze the correlation between serum miR-939 and miR-15b expression and mi-crovascular injury in patients with diabetic retinopathy(DR).Methods A total of 176 patients with type 2 di-abetes diagnosed and treated in the Baoding Second Hospital from January 2021 to October 2022 were selected as the study objects.The subjects were divided into 74 patients without DR(NDR group),62 patients with non-proliferative DR(NPDR group)and 40 patients with proliferative DR(PDR group)according to whether or not DR occurred and the degree of lesions.Real-time fluorescent quantitative PCR was used to detect the relative expression levels of miR-939 and miR-15b in serum of all groups,the level of vascular endothelial growth factor(VEGF)was detected by enzyme-linked immunosorbent assay,and the count percentage of en-dothelial cells(ECs),endothelial progenitor cells(EPCs)and circulating progenitor cells(CPCs)was detected by flow cytometry.Serum levels of miR-939,miR-15b,VEGF and ECs,EPCs and CPCs were compared in 3 groups.Pearson correlation was used to analyze the correlation between serum miR-939 and miR-15b and VEGF,ECs,EPCs and CPCs.Multivariate Logistic regression was used to analyze the factors affecting the oc-currence of DR in patients with type 2 diabetes.Results The relative expression levels of miR-939 and miR-15b in PDR group and NPDR group were lower than those in NDR group,while the serum VEGF levels were higher than those in NDR group,with statistical significance(P＜0.05).ECs in PDR group and NPDR group were higher than those in NDR group,while EPCs and CPCs were lower than those in NDR group,the differ-ence was statistically significant(P＜0.05).Serum miR-939 was negatively correlated with VEGF and ECs(r=-0.407,-0.613,P＜0.05),and positively correlated with EPCs and CPCs(r=0.481,0.486,P＜0.05).Serum miR-15b was negatively correlated with VEGF and ECs(r=-0.539,-0.625,P＜0.05),and positively correlated with EPCs and CPCs(r=0.451,0.483,P＜0.05).Multivariate Logistic regression anal-ysis showed that the duration of type 2 diabetes,hemoglobin A1c,2-hour postprandial blood glucose,VEGF,miR-939 and miR-15b were the influencing factors for the occurrence of DR in type 2 diabetes patients(P＜0.05).Conclusion The expression of miR-939 and miR-15b in serum of DR patients is closely related to VEGF,ECs,EPCs and CPCs,and the expression of miR-939 and miR-15b in serum of DR patients can provide a certain reference for early judgment and evaluation of the degree of microvascular injury.

Objective To develop a novel transcatheter tricuspid valve replacement device and test its performance. Methods The transcatheter tricuspid valve stent consisted of double-layer self-expanding nitinol stent, biotissue-derived bovine pericardial leaflets, and PTFE woven. The delivery system, mainly consisting of a handle control unit and a delivery sheath, was sent to the correct position via right atrium or jugular vein. The sheath had a visualization feature, and the handle control unit could realize the functions of stable release and partial recovery of the interventional valve. In addition, this study performed animal survival experiments on the basis of in vitro experiments. A large-white pig was used as the experimental animal. Cardiopulmonary bypass was established through median thoracotomy, then the right atrium was opened, and the interventional valve was released under direct vision without cardiac arrest. Approximately 1 month after interventional valve implantation, the maneuverability and stability of the interventional tricuspid device were evaluated by autopsy. Results Through the animal experiment, the interventional valve was successfully released, and the anchoring was satisfactory. Postoperative transthoracic echocardiography showed that the interventional valve opened and closed well, the flow rate of tricuspid valve was 0.6 m/s, and there was no obvious tricuspid regurgitation. One month after the operation, we dissected the large-white pig and found the interventional valve was not deformed or displaced, the leaflets were well aligned, and there was thrombus attachment in the groove between the inner and outer layers of the interventional valve. Conclusion Animal experiment shows that the novel device can stably and firmly attach to the tricuspid annulus, with good anchoring effect, and effectively reduce paravalvular leakage.

[Objective]To study the effect and mechanism of Chrysanthemi Indici Flos extract(CYM.E)on hyperuricemia in rats induced by"overeating greasy".[Methods]Sixty-four rats were randomly divided into normal control group,model control group,allopurinol 10mg·kg-1 group,Benzbromarone 5 mg·kg-1 group,and CYM.E 15,30,60 and 90 mg·kg-1 group,with 8 rats in each group.Except for the normal control group,the other groups used fat emulsion to establish a rat model of anthropomorphic hyperuricemia based on"overeating greasy".During the experiment,serum uric acid(UA),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-c)and low density lipoprotein cholesterol(LDL-c)levels were measured.Interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and lipopolysaccharide(LPS)were determined by enzyme linked immunosorbent assay(ELISA).The mRNA expression of TNF-α and Toll like receptor 4(TLR4)in the small intestine was measured by Real-time quantitative polymerase chain reaction(qRT-PCR);and the protein expression of TLR4 in the small intestine was measured by Western blot.Intestinal microecology was classified with operational taxonomic units(OTU),and OTU was analyzed with structure,and LEfSe difference,etc.[Results]CYM.E significantly reduced the serum UA,TC,LDL-c,IL-6 and TNF-αlevels of model rats;and reduced plasma LPS level.Moreover,CYM.E could reduce the expression of TNF-α mRNA and TLR4 mRNA in the small intestine,and reduced the protein expression of TLR4 in the small intestine,thus improving the microinflammatory state of the intestinal tract,increased the abundance and species of Lactobacillales and Bifidobacteriales,and reduced the abundance and species of Bacteroidales and Escherichia coli.[Conclusion]CYM.E has the effects of decreasing serum UA levels,regulating blood lipids,decreasing inflammatory damage,and decreasing endotoxin release,which may exert an UA-lowering effect by regulating intestinal microecology.

Idiopathic pulmonary fibrosis(IPF)is a progressive and inflammatory interstitial lung disease,clinically divided into stable and acute exacerbation periods of idiopathic pulmonary fibrosis(AE-IPF),which faces great difficulties in prevention and treatment,increasing the health and life burden of patients.At present,the diagnostic methods of AE-IPF are relatively limited,while biomarkers are safe,simple and specific,which are of great significance for the diagnosis and treatment of AE-IPF.Based on the theoretical connotation of AE-IPF(lung heat and collateral obstruction syndrome),this paper explores the application value of combining AE-IPF lung heat stagnation syndrome and biomarkers,explains the pathogenesis of AE-IPF lung heat stagnation syndrome at the molecular level,and analyzes the guiding role of combining syndromes and biomarkers in the clinical application of traditional Chinese medicine for AE-IPF lung heat stagnation syndrome.

The abundance of proteins in human urine is low and easily to be masked by high-abundance proteins during mass spectrometry analysis. Development of efficient and highly selective enrichment methods is therefore a prerequisite for achieving deep coverage of urine protein markers. Notably, different experimental methods would affect the urine protein enrichment efficacy and the coverage of urine proteome. In this study, ultrafiltration, nitrocellulose membrane enrichment and saturated ammonium sulfate precipitation were used to process 10 mL urine samples from five healthy volunteers and five bladder cancer patients. The urine proteins were enriched and separate by SDS-PAGE to compare the purification efficiency of different methods. Moreover, the peptide identification effects of different purification methods were analyzed by mass spectrometry to determine the best method for enriching urine protein histones. Saturated ammonium sulfate precipitation method outperformed the ultrafiltration and the nitrocellulose membrane enrichment methods in terms of the protein enrichment efficacy and quality. The interference of highly abundant albumin was reduced, whereas the amount of low-abundance protein was increased, and the sensitivity of mass spectrometry identification was increased. The saturated ammonium sulfate precipitation method may be applied for large-scale urine processing for screening clinical diagnostic markers through proteomics.
Histones ; Humans ; Mass Spectrometry ; Proteome ; Proteomics ; Urinalysis

Significant advances have been made in cancer immunotherapy recently, of which, bispecific antibodies (BsAbs), through bridging, redirecting and activating immune effector cells to kill cancer cells, are attracting increasing attention.Since the anti-CD19 and anti-CD3 BsAb, blinatumomab, was approved in 2014 by the FDA for the treatment of acute lymphoblastic leukemia, preclinical and clinical research with immune-cell-redirecting BsAbs have been fast growing in the area of hematologic malignancies. This review summarizes the current scientific and clinical investigation of BsAbs targeting different tumor-associated antigens from B lymphocytes, plasma cells and myeloid cells, covering three most common blood cancers, namely, lymphoma, multiple myeloma and leukemia. Further development for better therapeutic benefits and lower adverse events, are continuously being pursued, in particular, looking for more specific tumor antigens, optimizing antigen-antibody affinities, extending the half-life of BsAbs and redirecting different immune effector cells, whose breakthroughs and opportunities are soon to be delivered for the management of hematologic malignancies.