Rivaroxaban and Aspirin in Drug-Coated Balloon Angioplasty for Femoropopliteal In-Stent Restenosis: a retrospective cohort study.

BACKGROUND: After drug-coated balloon (DCB) treatment of the femoropopliteal artery in-stent restenosis (ISR), a certain proportion of patients also experience target lesion restenosis. The purpose of this study was to explore the efficacy and safety of rivaroxaban combined with aspirin in the treatment of ISR after DCB intervention. METHODS: Patients who underwent DCB treatment for ISR after femoropopliteal artery intervention at our center from March 2017 to February 2022 were included consecutively. According to the drug treatment after DCB intervention of ISR, the patients were divided into rivaroxaban and aspirin group (RA Group) and dual antiplatelet therapy (DAPT) group. The outcomes of two groups during the 12-month follow-up after DCB intervention were compared. RESULTS: A total of 92 patients were included in final analysis, with 43 in RA group and 49 in DAPT group. During 12-month follow-up, a total of 15 cases of recurrent ISR were detected, and the recurrence rate of ISR and clinically driven TLR in the RA group were lower than those in the DAPT group (P<0.05). The vascular patency rate in the RA group was higher than that in the DAPT group at 6 and 12 months of follow-up (P<0.05). During the follow-up, there were no adverse events such as death, myocardial infarction, stroke, amputation, or major bleeding, and only a total of 5 cases of minor bleeding occurred. CONCLUSION: Compared with the standard DAPT regimen, rivaroxaban combined with aspirin can safely improve the follow-up outcome after DCB for femoropopliteal ISR.

CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer.

Although oxaliplatin (OXA) is widely used in the frontline treatment of colorectal cancer (CRC), CRC recurrence is commonly observed due to OXA resistance. OXA resistance is associated with a number of factors, including abnormal regulation of pyroptosis. It is therefore important to elucidate the abnormal regulatory mechanism underlying pyroptosis. Here, we identified that the circular RNA circPDIA3 played an important role in chemoresistance in CRC. CircPDIA3 could induce chemoresistance in CRC by inhibiting pyroptosis both in vitro and in vivo. Mechanistically, RIP, RNA pull-down and co-IP assays revealed that circPDIA3 directly bonded to the GSDME-C domain, subsequently enhanced the autoinhibitory effect of the GSDME-C domain through blocking the GSDME-C domain palmitoylation by ZDHHC3 and ZDHHC17, thereby restraining pyroptosis. Additionally, it was found that the circPDIA3/miR-449a/XBP1 positive feedback loop increased the expression of circPDIA3 to induce chemoresistance. Furthermore, our clinical data and patient-derived tumor xenograft (PDX) models supported the positive association of circPDIA3 with development of chemoresistance in CRC patients. Taken together, our findings demonstrated that circPDIA3 could promote chemoresistance by amplifying the autoinhibitory effect of the GSDME-C domain through inhibition of the GSDME-C domain palmitoylation in CRC. This study provides novel insights into the mechanism of circRNA in regulating pyroptosis and providing a potential therapeutic target for reversing chemoresistance of CRC.

Serum VEGF, P-Selectin, HDL-C, Platelet Index, and Coagulation Function Index in Deep Vein Thrombosis after Traumatic Fracture.

BACKGROUND: The goal was to investigate the relationship between serum vascular endothelial growth factor (VEGF), P-selectin, high-density lipoprotein cholesterol (HDL-C), platelet parameters, and coagulation function indexes and postoperative deep vein thrombosis (DVT) in patients with traumatic fracture. METHODS: A total of 150 patients with traumatic fractures after DVT were selected as the DVT group, and 150 patients with traumatic fractures without DVT during the same period were selected as the non-DVT group. Serum VEGF, P-selectin, HDL-C, platelet parameters including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), platelet large cell ratio (P-LCR), and plasma coagulation function indexes including thrombin time (TT), prothrombin time (PT), activated partial thrombin time (APTT), fibrinogen (FIB), and D-dimer (D-D) were measured. Pearson's correlation was performed to analyze the correlation between serum VEGF, P-selectin, and coagulation function indexes, and binary logistic regression was used to analyze the risk factors of DVT. RESULTS: Serum VEGF and P-selectin in the DVT group were higher while HDL-C was lower than those in the non-DVT group (p < 0.05). Serum VEGF and P-selectin were negatively correlated with plasma D-D and FIB (p < 0.05), and serum HDL-C was negatively correlated (p < 0.05). Compared with the non-DVT group, MPV, PDW, and P-LCR in the DVT group were decreased (p < 0.05). Multivariate logistic regression analysis showed that P-LCR was a risk factor for postoperative DVT in patients with traumatic fractures (p < 0.05). CONCLUSIONS: Serum VEGF and P-selectin are higher and HDL-C is lower in patients with DVT after postoperative traumatic fracture than in patients without DVT. Combined detection of serum VEGF, P-selectin, HDL-C, and coagulation function indexes may help to reduce the risk of DVT. Platelet parameters (MPV, PDW, P-LCR) have certain reference values for the clinical diagnosis and disease evaluation of DVT.

Correlation between Serum MMP-2/-16 Levels and Inflammation in Patients with Deep Vein Thrombosis.

BACKGROUND: The aim of the study was to clarify the correlation between serum MMP-2/-16 and inflammation in patients with deep venous thrombosis (DVT). METHODS: Sixty DVT patients and 60 healthy people who underwent health examinations were collected. Serum MMP-2/-16, IL-6/-8, and TNF-α were determined by ELISA. MMP-2/-16 protein levels were detected by western blot, and IL-6/-8 and TNF-α by RT-qPCR. Correlation analysis was performed on MMP-2/-16xdd, IL-6/-8, and TNF-α in DVT patients. RESULTS: MMP-2/-16, IL-6/-8, and TNF-α in DVT patients after treatment were lower than before treatment. Serum IL-6/-8 and TNF-α levels in DVT patients were both positively correlated with MMP-2/-16 levels. CONCLUSIONS: MMP-2/-16 and inflammatory factors are related to DVT development, and IL-6/-8 and TNF-α are positively correlated with MMP-2/-16.

Characterization of an Enterococcus faecalis bacteriophage SFQ1 as a potential therapeutic agent.

Enterococcus faecalis is a well-established resident of the human gastrointestinal tract and is also a major cause of human infections. Unfortunately, therapeutic options for E. faecalis infections remain limited, particularly with the emergence of vancomycin-resistant strains in hospital settings. Consequently, there has been a renewed interest in phage therapy as an alternative to antibiotics. In this study, we have isolated a bacteriophage, vB_EfaS-SFQ1, from hospital sewage, which effectively infects E. faecalis strain EFS01. Phage SFQ1 is a siphovirus and exhibits a relatively broad host range. Furthermore, it has a short latent period of approximately 10 min and a large burst size of about 110 PFU/cell at a multiplicity of infection (MOI) of 0.01, and it could effectively disrupt the biofilms formed by E. faecalis. Thus, this study provides a detailed characterization of E. faecalis phage SFQ1, which has great potential for treating E. faecalis infections.

Neutrophil-to-Lymphocyte Ratio Predicts Restenosis After Drug-Coated Balloon Therapy for Femoropopliteal Artery Lesions: A Retrospective Study.

Background: Peripheral artery disease (PAD) is a common atherosclerotic vascular disease. The use of drug-coated balloon (DCB) for the treatment of femoropopliteal artery disease has gradually increased. A certain percentage of patients developed target lesion restenosis after DCB treatment of the femoral popliteal artery. The neutrophil-to-lymphocyte ratio (NLR) is closely related to the level of inflammatory activity and has predictive value for atherosclerotic vascular disease. This study aimed to analyze the relationship between NLR and 1-year restenosis after DCB for femoropopliteal artery disease. Methods: Patients with femoropopliteal artery disease who were treated with DCBs at our hospital from May 2016 to December 2020 were retrospectively included. Baseline data during the patient's first hospital stay and data during follow-up were collected. Demographic data, laboratory test results, lesion examination results, and major adverse events during the follow-up period were collected. Logistic regression was used to analyze the factors associated with restenosis after DCB. Results: A total of 117 patients were included. During 1-year follow-up, 19 cases (16.2%) of restenosis were detected. Five of these patients (4.3% of total included patients) were readmitted for symptomatic ischemia. No deaths or amputations occurred. Baseline NLR in patients with restenosis was higher than that in patients without restenosis (2.4 (2.1, 3.4) vs. 1.8 (1.3, 2.3), P < 0.001). Logistic univariate and multivariate analysis showed that baseline hs-CRP level (OR = 1.10, 95%CI: 1.05-1.34), lesion length (OR = 1.04, 95%CI: 1.02-1.27), use of rivaroxaban (OR = 1.08, 95%CI: 1.05-1.39), NLR (OR = 1.47, 95%CI: 1.13-2.48), LDL-C level (OR = 1.25, 95%CI: 1.05-1.52), and diabetes (OR = 1.25, 95%CI: 1.05-1.52) = 1.18, 95%CI: 1.06-1.66) were predictors of restenosis. Conclusion: Baseline NLR before DCB can predict the risk of restenosis after surgery.

Pharmacology of the giant panda (Ailuropoda melanoleuca) melanocortin-3 receptor.

The melanocortin-3 receptor (MC3R) is a member of the G protein-coupled receptor superfamily that plays a critical role in controlling energy balance and metabolism. Although pharmacological characterization of MC3R has been reported previously in several other species, there is no report on the MC3R from giant panda (Ailuropoda melanoleuca). This ancient species is known as a 'living fossil' and is among the most endangered animals in the world. Giant panda survive on a specialized diet of bamboo despite possessing a typical carnivorous digestive system. We report herein the molecular cloning and pharmacological characterization of amMC3R. Homology and phylogenetic analysis showed that amMC3R was highly homologous (>85%) to several other mammalian MC3Rs. Using human MC3R (hMC3R) as a control, the binding of five agonists, [Nle4, D-Phe7]-α-melanocyte stimulating hormone (NDP-MSH), α-, ß-, γ-, and D-Trp8-γ-MSH, was investigated, as well as Gs-cAMP and pERK1/2 signaling. The results showed that amMC3R bound NDP- and D-Trp8-γ-MSH with the highest affinity, followed by α-, ß-, and γ-MSH, with the same rank order as hMC3R. When stimulated with agonists, amMC3R displayed increased intracellular cAMP and activation of pERK1/2. These data suggest that the cloned amMC3R was a functional receptor. The availability of amMC3R and knowledge of its pharmacological functions will assist further investigation of its role in controlling energy balance and metabolism.

[Intramuscular injection of lentivirus-mediated EPAS1 gene improves hind limb ischemia and its mechanism in a rat model of peripheral artery vascular disease].

Objective To investigate the effect of over-expressed endothelial Per-Arnt-Sim domain protein 1 (EPAS1) on peripheral arterial disease (PAD) in a rat model. Methods PAD rat model was established by external iliac artery ligation followed by lentivirus-mediated EPAS1 gene injection into rat right adductor magnus. The models were evaluated by quantitative analysis of gait disturbance. The changes of blood flow in the posterior extremity of the rats were detected using laser Doppler. The expressions of EPAS1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) mRNAs were tested by real-time quantitative PCR. The expression of α-smooth muscle actin (αSMA) was detected by immunohistochemical staining. Results Compared with lenti-EGFP group, rat hind limb function and circulation got recovered obviously 7 days after lenti-EPAS1 injection. The mRNA expressions of EPAS1, HGF, bFGF, and VEGF were up-regulated in the lenti-EPAS1-treated sites.The expression of αSMA showed an obvious increase in the lenti-EPAS1-treated muscles. Conclusion Over-expressed lenti-EPAS1 can promote angiogenesis via the up-regulation of EPAS1-related angiogenic factors in the muscles of the affected hind limb and reduce gait disturbance.

[The combination of dasatinib and gefitinib enhances the killing effect of gefitinib on HCC827 lung cancer cells].

OBJECTIVE: To investigate the molecular mechanism underlying that dasatinib enhances the killing effect of gefitinib on HCC827 lung cancer cells. METHODS: HCC827 cells and gefitinib-resistant HCC827GR cells were treated with 0, 100, 500, 1000 nmol/L gefitinib alone or in combination with 1000 nmol/L dasatinib. The proliferation of HCC827 cells and HCC827GR cells was detected by MTT assay, the activity of caspase 3 was tested by spectrophotometry, and the protein phosphorylation levels of Src and epidermal growth factor receptor (EGFR) were examined by Western blotting. RESULTS: Src phosphorylation level was obviously enhanced in HCC827GR cells. Dasatinib significantly inhibited Src phosphorylation, promoted the cell proliferation and the expression of caspase 3. The combination of gefitinib and dasatinib had the stronger killing effect than gefitinib alone did. CONCLUSION: The combination of dasatinib and gefitinib can enhance the inhibition on the expression of Src protein and the killing effect of gefitinib on HCC827 lung cancer cells.