Endovascular Denervation for the Improvement of Limb Ischemia in Patients with Peripheral Artery Disease: A Randomized Clinical Trial.

BACKGROUND: To evaluate the safety and efficacy of endovascular denervation (EDN) as an adjunct to percutaneous vascular intervention (PVI) for peripheral artery disease (PAD). METHODS: From August 2019 to April 2021, 38 eligible patients with PAD enrolled in this study were randomly and equally assigned into 2 groups: the PVI group and the PVI + EDN group treated with EDN at the iliac and femoral arteries before PVI. The primary endpoint was the improvement in the ankle brachial index at 6 months after the procedure. The secondary endpoints were transcutaneous oxygen pressure (TcPO2), Rutherford category, numerical rating scale score, and safety. RESULTS: The technical success rates of PVI and EDN were 100%, and no device-related or procedure-related major adverse events occurred in either group. Compared with PVI alone, PVI + EDN demonstrated a significant improvement in limb hemodynamics at 6 months (Δ ankle brachial index 0.44 ± 0.31 vs. 0.24 ± 0.15, P = 0.018). Microcirculatory perfusion of PAD was significantly better at 6 months in the PVI + EDN group (ΔTcPO2, 15.68 ± 16.72 vs. 4.95 ± 13.43, P = 0.036). The Rutherford category was significantly improved in the PVI + EDN group in comparison with the PVI group at the 3-month follow-up (100.00% vs. 68.42%, P = 0.02). The decrease in the numerical rating scale score in the PVI + EDN group was greater than that in the PVI group at 1 week following the procedure (3 [2-5] vs. 4 [4-6], P = 0.022). CONCLUSIONS: In this single-center pilot analysis of a heterogeneous cohort of patients with PAD, PVI with EDN demonstrated a significant improvement in limb ischemia at 6 months compared with PVI alone.

Risk Factors for Access-Related Adverse Events Related to the Preclose Technique in Thoracic Endovascular Aortic Repair.

PURPOSE: To analyze the risk factors for access-related adverse events (AEs) of the preclose technique in thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Ninety-one patients with Stanford type B aortic dissection who underwent the preclose technique in TEVAR between January 2013 and December 2021 were included. According to the occurrence of access-related AEs, the patients were divided into 2 groups: those with AE and those without AE. Age, sex, combined diseases, body mass index, skin depth, femoral artery diameter, access calcification, iliofemoral artery tortuosity, and sheath size were recorded for risk factor analysis. The sheath-to-femoral artery ratio (SFAR), the ratio of the femoral artery inner diameter (in millimeters) to the sheath's outer diameter (in millimeters), was also included in the analysis. RESULTS: SFAR was identified as an independent risk factor for AEs using multivariable logistic analysis (odds ratio, 251.748; 95% CI, 7.004-9,048.534; P = .002). The cutoff value of SFAR was 0.85 and was related to a higher incidence of access-related AEs (5.2% vs 33.3%, P = .001), especially to a higher stenosis rate (0.0% vs 21.2%, P = .001). CONCLUSIONS: SFAR is an independent risk factor for access-related AEs of preclose in TEVAR with a cutoff value of 0.85. SFAR could be a new criterion for preoperative access evaluation in high-risk patients that may allow the detection and treatment of access-related AEs at the early stage.

A synchronous demodulation technology based on sample-and-hold for eddy current sensors.

This paper proposes a synchronous demodulation technology based on sample-and-hold which shows significant advantages in the application of precision sensors. The traditional synchronous demodulation methods are discussed, and then the working principle of the proposed method is theoretically analyzed in detail. It is found that the proposed method can not only effectively suppress the harmonic components caused by the signal source but is also beneficial to improving the dynamic range of precision sensors. The eddy current sensor is adopted as an example of precision sensors, and a high-precision eddy current displacement sensor prototype was designed and tested. The results show that with the proposed method, the harmonics in the output signal are suppressed more effectively, and the demodulation circuit is relatively simplified. This synchronous demodulation method has an extensive application prospect in precision sensors.

Thiourea participation in [3+2] cycloaddition with donor-acceptor cyclopropanes: a domino process to 2-amino-dihydrothiophenes.

The Yb(OTf)3-catalyzed [3+2] cycloaddition of donor-acceptor cyclopropanes with thiourea offers an efficient route to diverse 2-amino-4,5-dihydrothiophenes (up to 92% yield), in which optically active 2-amino-dihydrothiophenes can be produced from enantiomerically pure cyclopropanes. Thiourea, which is an odorless and cheap reagent, provides a C[double bond, length as m-dash]S double bond, serves as an amino source, and functions as a decarbalkoxylation reagent in this reaction. Preliminary mechanistic studies demonstrate that the reaction undergoes a sequential [3+2] cycloaddition/deamination/decarboxylation process.

Regulatory T cells demonstrate significantly increased functions following stimulation with IL-2 in a Tim-3-dependent manner in intracranial aneurysms.

The formation of intracranial aneurysm (IA) is associated with the destruction of various cellular and structural components, which induces pathogenic inflammatory responses that further propagate tissue damage. The regulatory immune system can suppress exacerbated inflammation and offer tissue protection; however, previous studies by others and us have demonstrated that the regulatory T (Treg) cells were functionally impaired in IA patients. Hence, strategies that can improve Treg function in IA patients should be investigated. Based on our previous finding that IL-2 strongly elevated the expression of the checkpoint molecule Tim-3 in Treg cells, we examined the effect of IL-2 in the function of Treg cells from IA patients. External IL-2 significantly improved the proliferation of Treg cells, increased the expression of CTLA-4 and LAG-3, and enhanced Treg-mediated suppression of conventional T cell (Tconv) proliferation. Importantly, compared to the Tim-3- Treg cells, the Tim-3+ Treg cells presented comparable proliferation capacity, but significantly greater expressions of CTLA-4 and LAG-3 and significantly higher capacity to suppress Tconv proliferation. In addition, blocking Tim-3 abrogated IL-2-mediated enhancement of Tim-3+ Treg cells. We then investigated the IL-2 level in IA patients, and found that although IA patients and healthy controls presented similar serum IL-2 concentration, the concentrations of IL-1ß and TNF-α were significantly higher in IA patients than in healthy controls, signaling a relative reduction in IL-2 abundance. Together, we found that IL-2 could significantly enhance the function of Treg cells from IA patients in a Tim-3-dependent manner.

Patients with intracranial aneurysms presented defects in regulatory T cells, which were associated with impairment in Tim-3 upregulation.

Pathogenic inflammation contributes to aneurysm formation by mediating the destruction of the endothelium and the extracellular matrix and promoting pathogenic proliferation of smooth muscle cells. In mouse models, tolerance-inducing T regulatory (Treg) cells could significantly reduce the incidence and severity of aneurysms. Hence, it should be investigated why in human intracranial aneurysm (IA) patients, Treg cells failed to provide protection against aneurysm formation. In this study, the frequency and function of Treg cells in IA patients were examined. The frequency of Foxp3+ Treg cells was significantly lower in IA patients than in healthy controls. This downregulation was only specific to the Treg subset of CD4+ T cells, as the frequency of total CD4+ T cell was increased in IA patients. Subsequently, we found that the expressions of Treg-associated molecules, including Foxp3, CTLA-4, TGF-ß, and IL-10, were significantly lower in Foxp3+ Treg cells from IA patients than in Foxp3+ Treg cells from healthy controls. In both healthy controls and IA patients, Foxp3+ Treg cells were distinguished into a more potent Tim-3+ subset and a less potent Tim-3- subset. The Tim-3+ subset of Foxp3+ Treg cells was significantly reduced in IA patients. Signaling via IL-2, IL-7, IL-15 and IL-21 was shown to promote Tim-3 upregulation in CD4+ and CD8+ T cells. Interestingly, we found that Tim-3 could be upregulated in Treg cells via the same mechanism, but compared to the Treg cells from healthy controls, the Treg cells from IA patients presented defects in Tim-3 upregulation upon cytokine stimulation. Together, our results demonstrated that Foxp3+ Treg cells in IA patients presented reduced function, which was associated with a defect in Tim-3 upregulation.

Soluble galectin 9 potently enhanced regulatory T-cell formation, a pathway impaired in patients with intracranial aneurysm.

Patients with intracranial aneurysm (IA) present a dysregulated immune system with lower frequency of regulatory T (Treg) cells. Here, we examined whether galectin 9 (Gal-9), the natural ligand of Tim-3, could promote Treg cells in IA patients. We first discovered that the intracellular and extracellular Gal-9 was primarily expressed by CD4+ CD25- T conventional (Tconv) cells, and also by monocytes at lower levels, but rarely by CD4+ CD25+ Treg cells. In IA patients, the Gal-9 expression was significantly lower than in healthy controls. CD4+ CD25- Tconv cells could be induced into Foxp3-expressing induced Treg (iTreg) cells using a TGF-ß-containing milieu. We found that soluble Gal-9 significantly enhanced this process by potently upregulating the expression of Foxp3, IL-10 and TGF-ß in a concentration-dependent manner. In addition, in the absence of additional Gal-9, the level of Foxp3 upregulation was directly correlated with the level of intrinsic Gal-9 expression. Notably, the strength of external Gal-9-mediated effects was significantly lower in IA patients than in healthy controls. Using a Tim-3 blocking antibody, we found that the promotion of iTreg development by soluble Gal-9 was dependent on the Tim-3 signalling pathway. Overall, our investigations demonstrated that Gal-9 presented a critical role in the development of iTreg cells. However, this mechanism was impaired in IA patients due to lower expression of both Gal-9 and Tim-3.

Bariatric Embolization of the Left Gastric Arteries for the Treatment of Obesity: 9-Month Data in 5 Patients.

PURPOSE: The purpose of this study is to investigate the safety and 9-month effectiveness of transcatheter left gastric artery embolization (LGAE) for treating patients with obesity. MATERIALS AND METHODS: The protocol of this study was approved by the Institutional Ethics Review Board. Five obese patients (3 men and 2 women) with mean weight of 102.0 ± 16.19 kg (range, 82.1-125.5 kg) and mean body mass index (BMI) of 38.1 kg/m2 ± 3.8 (range, 32.9-42.4 kg/m2) underwent LGAE with polyvinyl alcohol (PVA) particles in diameter of 500-710 µm. The primary endpoint was the safety by grading the adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0) within 30 days after LGAE. The secondary endpoints were measured with serum ghrelin and leptin levels, body weight, waist circumference, waist-to-height ratio, and abdominal fat quantity on MRI at the day immediately before LGAE and every 3 months after LGAE. RESULTS: LGAE was successfully performed in all patients. A superficial linear ulceration below the cardia was seen in 1 patient 3 days after LGAE and healed within 30 days. No other serious AEs (grade III or above) occurred. Average body weight loss at 3, 6, and 9 months was 8.28 ± 7.3 kg (p = 0.074), 10.42 ± 8.21 kg (p = 0.047), and 12.9 ± 14.66 kg (p = 0.121), respectively. The level of serum ghrelin decreased by 40.83% (p = 0.009), 31.94% (p = 0.107), and 24.82% (p = 0.151) at 3, 6, and 9 months after LGAE, respectively. There was minimal reduction of leptin levels at 3 and 6 months following LGAE (decreased by 0.26%, p = 0.929, and 4.33%, p = 0.427, respectively), but it declined obviously 9 months after LGAE (decreased by 11.22%, p = 0.295). Both waist circumference and waist-to-height ratio decreased after LGAE. MRI showed the area of subcutaneous adipose tissue decreased from the baseline of 400.90 ± 79.25 to 320.36 ± 68.06 cm2 (decreased by 20.09%, p = 0.006) at 3 months, to 328.31 ± 52.67 cm2 (decreased by 18.11%, p = 0.020) at 6 months, and to 286.40 ± 55.72 cm2 (decreased by 28.52%, p = 0.101) at 9 months after LGAE, respectively. But the decrease of abdominal fat loss at 9 months after LGAE was largely due to the reduction in visceral adipose tissue. CONCLUSIONS: Our study with 9-month data in 5 patients indicates that bariatric embolization of the LGA is a safe and may be a promising strategy to suppress the production of ghrelin and results in weight loss and abdominal fat reduction. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02786108).

Highly Enantioselective Synthesis of Chiral Cyclopropyl Nucleosides via Catalytic Asymmetric Intermolecular Cyclopropanation.

An efficient route to construct chiral cyclopropyl purine nucleoside analogues has been established via the catalytic asymmetric Michael-initiated ring-closure reactions of α-purine acrylates with α-bromo-carboxylic esters. Using (DHQD)2AQN as the catalyst, various chiral cyclopropyl purine nucleoside analogues with a chiral quaternary stereocenter were obtained in 72-98% yields, excellent diastereoselectivities, and 93-97% ee. Through simple functional group transformations, diverse chiral cyclopropyl purine nucleosides with hydroxymethyl group or carboxyl group were obtained.

High-capacity purification of hen egg-white proteins by ion-exchange electrochromatography with an oscillatory transverse electric field.

The ion-exchange electrochromatography with an oscillatory electric field perpendicular to the mobile-phase flow driven by pressure (pIEEC) was used to separate hen egg-white (HEW) proteins. The results were compared with those of normal ion-exchange chromatography (IEC). The column was designed as three-compartment rectangular column of 2-mL with dimensions (length x width x depth) of 40 x 10 x 5 mm(3) and the electric field was applied across the direction of column width. Q Sepharose FF was packed into the central compartment as the chromatographic bed. It was confirmed that the dynamic binding capacity (DBC) of different proteins (ovotransferrin and ovalbumin) in the HEW solution increased 2.3 times when an oscillatory electric current of 30 mA at 1/20 Hz was applied in the transverse column direction. Then, the HEW proteins were separated by the pIEEC at loading amounts 2.3-fold higher than those by the IEC. When the feedstock of about one-third of the DBC was applied to the columns (i.e., 7 mL for the pIEEC and 3 mL for the IEC), similar separation efficiencies of the two chromatographic modes were achieved. Both the recovery yield and purity reached 73% to over 90%. The results indicate that the pIEEC is promising for high-capacity purification of proteins.