Clinical and historical infection of Tacheng tick virus 2: A retrospective investigation.

BACKGROUND: Tacheng tick virus 2 (TcTV-2) is an emerging tick-borne virus belonging to the genus Uukuvirus in the family Phenuiviridae. Initially isolated in 2019 from a patient in Xinjiang Uygur Autonomous Region (XUAR), northwestern China, who developed fever and headache after a tick bite, TcTV-2 was concurrently molecularly detected in hard ticks across various countries, including China, Kazakhstan, Romania, and Turkey. This study conducted a retrospective epidemiological investigation of TcTV-2 infection. METHODOLOGY: In this retrospective cohort study, we collected samples from 47 tick-bitten patients, 984 herdsmen, 7 Asian badgers, 13 red foxes, and 168 Hyalomma asiaticum tick egg batches. Patients' samples were primarily analyzed by using high-throughput sequencing, targeting the V3-V4 region of the bacterial 16S rRNA gene and viral cDNA libraries. Typical tick-borne pathogens were further confirmed using RT-PCR and detected in Asian badgers, red foxes and Hy. asiaticum tick egg batches. We also conducted enzyme-linked immunosorbent assay (ELISA) to detected specific IgM and IgG antibodies against TcTV-2 in herdsmen. Phylogenetic analysis was performed to genetically characterize TcTV-2 detected in this study. PRINCIPAL FINDINGS: TcTV-2 was detected in various samples, including blood, urine, and throat swabs from 12.77% (6/47) tick-bitten patients. It was found in blood samples of 14.29% (1/7) of wild badgers, 7.69% (1/13) of red foxes, and 13.69% (23/168) of Hy. asiaticum egg batches. Furthermore, ELISA results revealed that 9.55% (94/984) of the serum samples (34 from males and 60 from females) were tested positive for TcTV-2-specific IgG, while 2.95% (29/984, 7 males and 22 females) showed positivity for TcTV-2-specific IgM. Additionally, 1.02% (10/984, 4 males and 6 females) of the sera tested positive for both TcTV-2-specific IgM and IgG. Phylogenetic analysis indicated that the TcTV-2 strains detected in this study were genetically similar, regardless of their origin and host species. CONCLUSIONS: Clinical symptoms of TcTV-2 infection in patients are nonspecific, with common symptoms including headache, fever, asthenia, vomiting, myalgia, rash, and meningitis-like signs. TcTV-2 can be detected in blood, urine, and throat swab samples of infected patients. Among local herdsmen, 9.55% tested positive for TcTV-2-specific IgG and 2.95% for TcTV-2-specific IgM. Importantly, TcTV-2 can be transovarially transmitted in Hy. asiaticum ticks, and the Asian badgers and red foxes are potential reservoirs of TcTV-2.

Effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen for diabetic foot ulcers.

Diabetic foot ulcers were a significant complication of diabetes and were accompanied by delayed wound healing. To compare the effect of topical application electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) dressing with alginate dressing when treating diabetic foot ulcers (DFUs). A single-center, prospective, randomized, patient-blinded clinical trial was conducted from July 1, 2023, to December 26, 2023. The clinical trial registration was completed on August 28, 2023 (ClinicalTrials.gov Identifier: NCT06014437). The eligible patients with DFUs of 1-20 cm2 present for at least 1 month and with Wagner grade 1 or 2. They were randomized 1:1 to receive PLCL/Fg or alginate dressing. Participants received PLCL/Fg dressing 1-3 times per week or alginate dressing 3 times per week for 12 weeks. A total of 52 patients (33 men [63.5 %]; mean [SD] age, 63.1 [11.9] years; mean [SD] diabetes time, 8.3 [4.6] years) with DFUs were assessed for this study. The DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 3.8 [3.2] cm2) were randomized to receive either the PLCL/Fg dressing (n = 26) or the alginate dressing (n = 26) for as long as 12 weeks. In this study, the incidence of complete healing included 22 patients (91.7 %) in the PLCL/Fg group and 14 (63.6 %) in the alginate group during the 12-week treatment period (P = 0.003). The treatment-related adverse events that occurred were 5 (20.8 %) in the PLCL/Fg group and 4 (18.1 %) in the comparator group. In this randomized clinical trial, PLCL/Fg dressing showed beneficial effects in DFUs treatment of wound surface reduction and regulating the wound microenvironment.

Bactericidal and biofilm eradication efficacy of a fluorinated benzimidazole derivative, TFBZ, against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major inducement of nosocomial infections and its biofilm formation render the high tolerance to conventional antibiotics, which highlights the requirement to develop new antimicrobial agents urgently. In this study, we identified a fluorinated benzimidazole derivative, TFBZ, with potent antibacterial efficacy toward planktonic MRSA (MIC = 4 µg/mL, MBC = 8 µg/mL) and its persistent biofilms (≥99%, MBEC = 8 µg/mL). TFBZ manifested significant irreversible time-dependent killing against MRSA as characterized by diminished cell viability, bacterial morphological change and protein leakage. Furthermore, the results from CBD devices, crystal violet assay in conjunction with live/dead staining and scanning electron microscopy confirmed that TFBZ was capable of eradicating preformed MRSA biofilms with high efficiency. Simultaneously, TFBZ reduced the bacterial invasiveness and exerted negligible hemolysis and cytotoxicity toward mammalian cells, which ensuring the robust therapeutic effect on mouse skin abscess model. The transcriptome profiling and quantitative RT-PCR revealed that a set of encoding genes associated with cell adhesion, biofilm formation, translation process, cell wall biosynthesis was consistently downregulated in MRSA biofilms upon exposure to TFBZ. In conclusion, TFBZ holds promise as a valuable candidate for therapeutic applications against MRSA chronic infections.

Outcomes of Excimer Laser Ablation Combined with Drug-coated Balloon in Atherosclerotic Lesions of the Popliteal Artery.

BACKGROUND: The treatment of atherosclerotic lesions in the popliteal artery is challenging. This study aims to investigate the efficacy and safety of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for these lesions. METHODS: From June 2019 to December 2021, data of patients who underwent ELA combined with DCB in the popliteal artery were retrospectively reviewed. Demographics, lesion characteristics, periprocedural complications, and follow-up information were analyzed. The primary endpoint was primary patency. Secondary endpoints included major amputation-free survival rate, technical success, bailout stenting, clinically-driven target lesion reintervention, improvement of ankle-brachial index (ABI), and Rutherford class. RESULTS: A total of 61 patients were enrolled. The mean age was 73.4 ± 11.7 years. 20 (32.8%) patients had stenotic lesions, while 41 (67.2%) patients had chronic total occlusions. The mean length of these lesions was 7.3 ± 2.8 cm. Procedure technical success rate was 95.1%. Bailout stent was performed in 3 (4.9%) patients. Intraprocedural distal embolization occurred in 3 (4.9%) patients, while flow limiting dissections occurred in 3 (4.9%) patients. The mean ABI was significantly improved from 0.45 ± 0.13 at baseline to 0.90 ± 0.12 after ELA, 0.88 ± 0.11 at 6 months and 0.85 ± 0.12 at 12 months during the follow-up period. The median follow-up time was 28.2 ± 6.1 months. Reintervention was performed in 5 (8.2%) patients. The 2-year primary patency was 83.5%. CONCLUSIONS: ELA combined with DCB is a safe and effective strategy in the treatment of popliteal artery atherosclerotic lesions with low rates of bail-out stenting and high primary patency.

Platelet factor 4 promotes deep venous thrombosis by regulating the formation of neutrophil extracellular traps.

The presence of neutrophil extracellular traps (NETs) in thrombotic diseases has been extensively studied. The exact mechanism of NET formation in deep venous thrombosis (DVT) has not been largely studied. This study is aimed to explore the role of NETs and their interaction with platelet factor 4 (PF4) in DVT. In plasma samples from 51 healthy volunteers and 52 DVT patients, NET markers and PF4 were measured using enzyme-linked immunosorbent assays (ELISA). NET generation in blood samples from healthy subjects and DVT patients was analyzed by confocal microscopy and flow cytometry. The plasma levels of NETs were significantly elevated in DVT patients, and neutrophils from patients showed a stronger ability to generate NETs after treatment. PF4 was upregulated in plasma samples from DVT patients and mediated NET formation. NETs enhanced procoagulant (PCA) via tissue factor and activating platelets to induce procoagulant activity. In addition, we established an inferior vena cava ligation (IVC) model to examine the role of NETs in thrombogenicity in DVT. In conclusion, NET formation was mediated by PF4 and enhance the procoagulant activity in DVT.

Numerical simulation of the distal stent graft-induced new entry after TEVAR.

The study aimed to investigate the mechanical factors for distal stent graft-induced new entry (dSINE) in aortic dissection patients and discussed these factors in conjunction with aortic morphology. Two patients (one dSINE and one non-dSINE), with the same age, gender, and type of implanted stent, were selected, then aortic morphological parameters were calculated. In addition, the stent material parameters used by the patients were also fitted. Simulations were performed based on the patient's aortic model and the stent graft used. The true lumen segment at the distal stent graft was designated as the "dSINE risk zone," and mechanical parameters (maximum principal strain, maximum principal stress) were computed. When approaching the area with higher mechanical parameters in the dSINE risk zone, dSINE patient exhibited higher values and growth rates in mechanical parameters compared to non-dSINE patient. Furthermore, dSINE patient also presented larger aortic taper ratio, stent oversizing ratio, and expansion mismatch ratio of the distal true lumen (EMRDTR). The larger mechanical parameters and growth rates in dSINE patient corresponded to a greater aortic taper ratio, stent oversizing ratio, and EMRDTR. The failure of dSINE prediction by the stent tortuosity index indicated that mechanical parameters were the fundamental reasons for dSINE development.

Endovascular Strategies and Outcomes for Aberrant Splenic Artery Aneurysms.

OBJECTIVES: Aberrant splenic artery aneurysms (ASAAs) located at the splenomesenteric trunk (SMT) and the celiacomesenteric trunk have a close anatomical relationship with the superior mesenteric artery (SMA). The aim of this study was to review our institutional experience of endovascular treatment for ASAAs and evaluate the long-term outcomes. METHODS: A retrospective review of patients with ASAAs who underwent endovascular treatment between December 2006 and December 2022 was performed. The demographics of the patients, aneurysm characteristics, treatment strategies, perioperative and long-term outcomes, and complications were analyzed. RESULTS: A total of 29 patients with ASAAs were endovascularly treated at our institution. The SMT variant occurred in the majority of the patients. All ASAAs were characterized by eccentric growth and extremely short inflow arteries. Only 1 patient's inflow artery of the aneurysm exceeded 1 cm in length. Thirteen patients were treated by coil embolization alone. Four patients received bare stent-assisted coil embolization. A combination of coil embolization and covered stent placement across the orifice of the aberrant splenic artery was performed in the remaining 12 cases. Coil migration into the SMA occurred in 2 patients during the operation. Technical success was achieved in all patients. With a median duration of 63 (34-101) months of follow-up, no intestinal ischemia, aneurysm-related death, aneurysm rupture, or sac enlargement occurred. Three cases of aneurysm sac reperfusion were observed, and 1 patient underwent reintervention with secondary embolization. Asymptomatic occlusion of the covered stent was detected in 1 patient at 2 years. CONCLUSIONS: Endovascular treatment is a safe, effective, and durable option for ASAAs. Inflow embolization might be difficult to achieve in ASAAs and poses a high risk of coil migration into the SMA. Long-term observation indicates that reasonable use of the covered stent could achieve reliable inflow artery exclusion in ASAAs without intestinal complications. CLINICAL IMPACT: Aberrant splenic artery aneurysm (ASAA) is an extremely rare entity. This study reported a large sample size of ASAAs treated by endovascular techniques with long-term follow-up. The ASAA was characterized by an extremely short inflow artery and a close anatomical relationship with the superior mesenteric artery (SMA). Endovascular treatment is a safe, effective, and durable option for ASAAs. Inflow embolization might be difficult to achieve in ASAAs and pose a high risk of coil migration into the SMA. Long-term observation indicates that reasonable use of the covered stent could achieve reliable inflow artery exclusion in ASAAs without intestinal complications.

Prognostic Implications of Initial Focal Contrast Enhancement in Acute Type B Intramural Hematoma.

BACKGROUND: The prognostic implication of initial focal contrast enhancement (FCE), including focal intimal disruption (FID) and intramural blood pool (IBP), in acute type B intramural hematoma (IMH) remain unclear. OBJECTIVES: The purpose of this study was to compare the prognostic implications in IMH with or without FCE. METHODS: A total of 574 patients were enrolled. FID was defined as an intimal disruption with contrast-filled out-pouching from the aorta lumen with a communicating orifice of >3 mm, and IBP was defined as a localized contrast medium-filled pool inside the IMH. RESULTS: A total of 207 (36.1%) patients with initial FCE, including 132 (63.8%) FIDs and 75 (36.2%) IBPs, were identified. Patients with FCE accompanying IMH were more likely to have hypertension (P = 0.001), pleural effusion (P = 0.006), fewer aortic segments involved (P < 0.001), more adverse aortic events (AAEs) (P < 0.001), and fewer freedom from intervention (P = 0.002). Pleural effusion (HR: 1.79; 95% CI: 1.25-2.55; P = 0.001) and FCE (HR: 1.51; 95% CI: 1.12-2.02; P = 0.006) were identified to be the independent risk factors of AAEs. In the subgroup analysis, IMH with initial FID were more likely to progress than those with initial IBP (P < 0.001). FIDs located at the proximal descending aorta (HR: 2.95; 95% CI: 1.65-5.29; P < 0.001) were associated with AAEs. CONCLUSIONS: Patients with FCE accompanying IMH were more likely to progress, especially in those initial FID localized at the proximal descending aorta. (Nature course and predictors of progression of intramural hematoma: A retrospective, multicenter study; ChiCTR2300073829).

Towards biomechanics-based pre-procedural planning for thoracic endovascular aortic repair of aortic dissection.

BACKGROUND AND OBJECTIVE: Although thoracic aortic endovascular repair (TEVAR) has shown promising outcomes in the treatment of patients with complicated type B aortic dissection, complications still occur after TEVAR that can lead to catastrophic events. Biomechanical interactions between the stent-graft (SG) and the local aortic tissue play a critical role in determining the outcome of TEVAR. Different SG design may cause different biomechanical responses in the treated aorta, but such information is not known at the time of pre-procedural planning. By developing patient-specific virtual stent-graft deployment tools, it is possible to analyse and compare the biomechanical impact of different SGs on the local aorta for individual patients. METHODS: A finite element based virtual SG deployment model was employed in this study. Computational simulations were performed on a patient-specific model of type B aortic dissection, accounting for details of the SG design and the hyperelastic behaviour of the aortic wall. Based on the geometry reconstructed from the pre-TEVAR CTA scan, the patient-specific aortic dissection model was created and pre-stressed. Parametric models of three different SG products (SG1, SG2 and SG3) were built with two different lengths for each design. The SG models incorporated different stent and graft materials, stent strut patterns, and assembly approaches. Using our validated SG deployment simulation framework, virtual trials were performed on the patient-specific aortic dissection model using different SG products and varying SG lengths. CONCLUSION: Simulation results for different SG products suggest that SG3 with a longer length (SG3-long) would be the most appropriate device for the individual patient. Compared to SG1-short (the SG deployed in the patient), SG3-long followed the true lumen tortuosity closely, resulted in a more uniform true lumen expansion and a significant reduction in peak stress in the distal landing zone. These simulation results are promising and demonstrate the feasibility of using the virtual SG deployment model to assist clinicians in pre-procedural planning.

Predictors of Return to Work After Thoracic Endovascular Aortic Repair in Patients With Type B Aortic Dissection.

OBJECTIVE: Type B aortic dissection (TBAD) is a life-threatening condition, and it takes heavy burden to family and society. Return to work (RTW) not only means patients' physical health but also demonstrates their mental well-being. Thoracic endovascular aortic repair (TEVAR) has been successful in treatment of TBAD patients. However, less studies have addressed on the social functional recovery of TBAD after TEVAR, especially for RTW. METHODS: From January 1, 2017 to January 1, 2021, TBAD patients who underwent TEVAR and completed a 12-month follow-up were retrospectively enrolled. Primary outcome was RTW. Patients' demographic, sociological, and clinical characteristics, and so on were recorded to analyze and demonstrate independent risk factors for RTW. RESULTS: Four hundred thirty-two TBAD patients (388 males) were enrolled with a mean age of 48.3±8.9 years (ranged from 19 to 60 years). The 12-month cumulative RTW rate was 62.7% (95% confidence interval [CI]: 57.2%-67.8%). Age <50 years (odds ratio [OR]=3.675, 95% CI: 1.436-9.405) was identified as independent protective factors for RTW, while preoperative job as manual workers (OR=0.101, 95% CI: 0.029-0.353), average annual income, <30 000 Chinese Yuan (CNY) [<4400 US dollar], (OR=0.186, 95% CI: 0.054-0.637), complicated TBAD (malperfusion) (OR=0.246, 95% CI: 0.092-0.659), and distal stent graft-induced new entry (SINE) (OR=0.218, 95% CI: 0.083-0.575, p=0.002) were identified as independent risk factors. CONCLUSION: Approximately 64% of our patients were able to RTW in the 12 months post-TEVAR for TBAD. Younger patients, patients with less physically demanding jobs, and patients with less complex surgeries were more likely to RTW. Based on these results, more can be done to facilitate the patient's ability and willingness to RTW after TEVAR. CLINICAL IMPACT: Type B aortic dissection (TBAD) is a life-threatening condition that poses significant burden on both individuals and society. The ability to return to work (RTW) not only reflects the patient's physical health but also indicates their mental well-being. Therefore, identifying risk factors for RTW and promoting the reintegration of TBAD patients into the workforce is crucial in clinical practice.To our knowledge, this study is the first to elucidate and predict the RTW outcomes of TBAD patients who underwent thoracic endovascular aortic repair (TEVAR).

Risk factors for at-risk foot and peripheral artery disease among the population with diabetes: A multicommunity-based cross-sectional study.

AIMS: This study aimed to investigate the prevalence, characteristics, and influence factors of the at-risk foot with diabetes mellitus (DM). METHODS: This study included 3030 DM patients from the at-risk foot screening program of Shanghai in China between March 21 and April 30 in 2021. Data were collected from the questionnaire survey, physical examination, and fasting blood sample. RESULTS: The prevalence of at-risk foot was 27.8% among DM patients. After adjusted, the risk of higher at-risk grade increased with age and urinary albumin creatinine ratio (OR = 1.04, 95%CI = 1.02-1.06; OR = 1.001, 95%CI = 1.000-1.002, respectively), whereas decreased with estimated glomerular filtration rate (eGFR) (OR = 0.991, 95%CI = 0.984-0.998). The incidence of peripheral artery disease (PAD) was 11.1% in all people with DM, and age, pulse rate, and low-density lipoprotein were independent risk factors for PAD. In contrast, high-density lipoprotein, eGFR, and lymphocyte-to-monocyte ratio were independent protective factors for PAD. Glycated hemoglobin HbA1c was not an independent risk factor for increased risk grade or more severe PAD. CONCLUSIONS: The at-risk foot accounted for a high percentage among DM patients. Advanced age and renal dysfunction are independent risk factors for the at-risk foot. Glycemic control does not reduce the risk grade of at-risk foot and the incidence of PAD.

Nonsurgical Repair of the Ascending Aorta: Why Less Is More.

Objective: Advanced endovascular options for acute and chronic pathology of the ascending aorta are emerging; however, several problems with stent grafts placed in the ascending aorta have been identified in patients unsuitable for surgical repair, such as migration and erosion at aorta interface. Method: Among the six cases analysed in this report, three were treated with a stent graft in the ascending aorta to manage chronic dissection in the proximal aorta; dimensions of those stent grafts varied between 34 and 45 mm in diameter, and from 77 to 100 mm in length. Three patients, matched by age, sex and their nature of pathology, were subjected to the focal closure of a single communicating entry by the use of an occluding device (Amplatzer ASD and PFO occluders between 14 and 18 mm disc diameter) with similar Charlson comorbidity score. Results: Both conceptually different nonsurgical management strategies were technically feasible; however, with stent grafts, an early or delayed erosion to full re-dissection was documented with stent grafts, in contrast to complete seal, with an induced remodelling and a long-term survival after the successful placing of coils and occluder devices. Moreover, aortic root motion was not impaired by the focal occlusion of a communication with an occluder, while free motion was impeded after stent graft placement. Conclusions: The intriguing observation in our small series was that stent grafts placed in the ascending aorta portends the risk of an either early (post-procedural) or delayed migration and erosion of aortic tissues at the landing site or biological interface between 12 and 16 months after the procedure, a phenomenon not seen with the use of focal occluding devices up to 5 years of follow-up. Obviously, the focal approach avoids the erosion of the aortic wall as the result of minimal interaction with the biological interface, such as a diseased aortic wall. Potential explanations may be related to a reduced motion of the aortic root after the placement of stent graft in the ascending aorta, whereas the free motion of aortic root was preserved with an occluder. The causality of erosion may however not be fully understood, as besides the stiffness and radial force of the stent graft, other factors such as the induced inflammatory reactions of aortic tissue and local adhesions within the chest may also play a role. With stent grafts failing to portend long-term success, they may still have a role as a temporizing solution for elective surgical conversion. Larger datasets from registries are needed to further explore this evolving field of interventions to the ascending aorta.

Evaluation of the lower extremity blood supply in no-option critical limb ischemia patients with stem cell transplantation by time maximum intensity projection CT perfusion: A single-centre prospective study.

OBJECTIVES: Cell therapy has had satisfactory safety and efficacy outcomes for no-option critical limb ischaemia (NO-CLI) patients. In the current study, we aimed to compare the image quality of ischaemic lower limb blood vessels shown on volumetric CT-based time maximum intensity projection CT perfusion (t-MIP CTP) versus single-phase CTA (sCTA). We also tried to quantify the blood flow of the ischaemic lower extremity based on the t-MIP technique, not only to precisely show the dynamic change in blood flow from before to after cell therapy but also to detect any relationship between this change and patient prognosis. METHODS: A total of 31 patients with thromboangiitis obliterans (TAO)-induced NO-CLI who had been referred from the department of vascular surgery to undergo autologous stem cell transplantation into a single limb from January 2020 to March 2021 were prospectively enrolled in this study. Preoperative sCTA or t-MIP CTP and postoperative 1-month t-MIP CTP were performed in all patients. Clinical outcomes, including the 1-month ankle-brachial index (ABI) and 3-month CLI status, were also analysed. Image quality, including objective scores (attenuation, signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]), subjective scores and collateral scores, was compared between preoperative sCTA and t-MIP CTP. Vascular volume was calculated as the total volume (mL) of lower limb arteries within the scanning range. All images and calculations were performed by 2 separate radiologists. Receiver operating characteristic curves were drawn to reveal the sensitivity and specificity of vascular volume and ABI in predicting prognosis. RESULTS: Both sCTA and t-MIP CTP images exhibited good quality for diagnosis. t-MIP CTP images showed significantly higher attenuation, SNR and CNR in all arterial segments (popliteal artery, anterior tibial artery, posterior tibial artery and peroneal artery). In subjective and collateral score evaluations, t-MIP CTP images were also significantly better than sCTA images (both p < .05). At 1 month after transplantation, both vascular volume and ABI showed significant improvement (both p < .01). At 3 months after transplantation, 38.71% of patients (12/31) achieved CLI relief (Rutherford class < 4). Through the receiver operating characteristic (ROC) curve, the 1-month vascular volume increase ratio showed better ability to predict the 3-month prognosis (radiologist 1: AUC, 0.757; sensitivity, 0.750; specificity, 0.840; radiologist 2: AUC, 0.803; sensitivity, 0.500; specificity, 1.000) than the 1-month ABI increase ratio (AUC, 0.607; sensitivity, 0.230; specificity, 0.820) or 1-month ABI (AUC, 0.410; sensitivity, 0.080; specificity, 0.580). CONCLUSION: t-MIP CTP showed significantly higher-quality images of ischaemic limb vascularity than sCTA. t-MIP CTP can reveal the anatomical information of collaterals more accurately, which is of great importance for NO-CLI patients undergoing cell transplantation. The 1-month vascular volume increase ratio can predict the 3-month prognosis more precisely on this basis.

Hemodynamic parameters impact the stability of distal stent graft-induced new entry.

Stent graft-induced new entry tear (SINE) is a serious complication in aortic dissection patients caused by the stent-graft itself after thoracic endovascular aortic repair (TEVAR). The stability of SINE is a key indicator for the need and timing of reinterventions. This study aimed to understand the role of hemodynamics in SINE stability by means of computational fluid dynamics (CFD) analysis based on patient-specific anatomical information. Four patients treated with TEVAR who developed a distal SINE (dSINE) were included; two patients had a stable dSINE and two patients experienced expansion of the dSINE upon follow-up examinations. CFD simulations were performed on geometries reconstructed from computed tomography scans acquired upon early detection of dSINE in these patients. Computational results showed that stable dSINEs presented larger regions with low time-averaged wall shear stress (TAWSS) and high relative residence time (RRT), and partial thrombosis was observed at subsequent follow-ups. Furthermore, significant systolic antegrade flow was observed in the unstable dSINE which also had a larger retrograde flow fraction (RFF) on the SINE plane. In conclusion, this pilot study suggested that high RRT and low TAWSS may indicate stable dSINE by promoting thrombosis, whereas larger RFF and antegrade flows inside dSINE might be associated with its expansion.

A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension.

AIMS: Excess dietary sodium intake and retention lead to hypertension. Impaired dermal lymphangiogenesis and lymphatic dysfunction-mediated sodium and fluid imbalance are pathological mechanisms. The adenosine A2A receptor (A2AR) is expressed in lymphatic endothelial cells (LECs), while the roles and mechanisms of LEC-A2AR in skin lymphangiogenesis during salt-induced hypertension are not clear. METHODS AND RESULTS: The expression of LEC-A2AR correlated with lymphatic vessel density in both high-salt diet (HSD)-induced hypertensive mice and hypertensive patients. Lymphatic endothelial cell-specific A2AR knockout mice fed HSD exhibited 17 ± 2% increase in blood pressure and 17 ± 3% increase in Na+ content associated with decreased lymphatic density (-19 ± 2%) compared with HSD-WT mice. A2AR activation by agonist CGS21680 increased lymphatic capillary density and decreased blood pressure in HSD-WT mice. Furthermore, this A2AR agonist activated MSK1 directly to promote VEGFR2 activation and endocytosis independently of VEGF as assessed by phosphoprotein profiling and immunoprecipitation assays in LECs. VEGFR2 kinase activity inhibitor fruquintinib or VEGFR2 knockout in LECs but not VEGF-neutralizing antibody bevacizumab suppressed A2AR activation-mediated decrease in blood pressure. Immunostaining revealed phosphorylated VEGFR2 and MSK1 expression in the LECs were positively correlated with skin lymphatic vessel density and A2AR level in hypertensive patients. CONCLUSION: The study highlights a novel A2AR-mediated VEGF-independent activation of VEGFR2 signaling in dermal lymphangiogenesis and sodium balance, which might be a potential therapeutic target in salt-sensitive hypertension.

Preclinical animal study of electrospun poly (l-lactide-co-caprolactone) and formulated porcine fibrinogen for full-thickness diabetic wound regeneration.

Diabetic foot ulcer is one of the most serious chronic complications of diabetes mellitus. It may lead to amputation of the lower extremities for diabetics. Our study was to evaluate the effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) wound dressing on animal wound model. A blend ratio of PLCL/Fg scaffold was 4 (PLCL):1 (Fg). The scanning electron microscopy findings showed that the fibers' diameter was 122.5 ± 80.3 nm, and the tensile strength was 9.2 ± 0.2 MPa. In-vivo study of the hog normal model demonstrated that PLCL/Fg dressing had better biocompatibility, degradability, and ability to restore the skin's normal structure. We evaluated the wound healing processes in the rat diabetic model by macroscopic observation and histological observation at 1, 2, and 3 post-operation weeks. In our study, the PLCL/Fg group performed better 3 weeks after surgery, in terms of macroscopic healing and scarring. After surgery, the PLCL/Fg group showed better fibroblast accumulation, tissue granulation, and collagen expression than the control group. Topical treatment with PLCL/Fg dressing effectively enhanced wound healing in both normal and hyperglycemic conditions, suggesting that it may possess wound-healing potential.