Iatrogenic Pseudoaneurysm with Acute Arterial Thrombosis in Multiple Branches of the Lower Limbs Treated by Ultrasound-guided Thrombin Injection: A Case Report.

INTRODUCTION: With the development of vascular intervention, pseudoaneurysm complications are increasing. Ultrasound-guided thrombin injection (UGTI) is currently the treatment of choice for pseudoaneurysm, but the pharmacological properties of thrombin may trigger acute thrombosis within the vessel lumen. Despite a very low incidence, this type of primary arterial thrombosis is a serious complication of UGTI, and cases involving multiple branches of the lower limb arteries are particularly rare. CASE PRESENTATION: Here, we report a case of a 65-year-old male who underwent UGTI for the treatment of an iatrogenic pseudoaneurysm of the femoral artery complicated by acute thrombosis of multiple arteries in the lower limbs, and the patient ultimately underwent a successful thrombectomy. CONCLUSION: We reviewed the case and analyzed the possible etiologic causes, providing a reference for future clinical work.

Microcarriers promote the through interface movement of mouse trophoblast stem cells by regulating stiffness.

Mechanical force is crucial in the whole process of embryonic development. However, the role of trophoblast mechanics during embryo implantation has rarely been studied. In this study, we constructed a model to explore the effect of stiffness changes in mouse trophoblast stem cells (mTSCs) on implantation: microcarrier was prepared by sodium alginate using a droplet microfluidics system, and mTSCs were attached to the microcarrier surface with laminin modifications, called T(micro). Compared with the spheroid, formed by the self-assembly of mTSCs (T(sph)), we could regulate the stiffness of the microcarrier, making the Young's modulus of mTSCs (367.70 ± 79.81 Pa) similar to that of the blastocyst trophoblast ectoderm (432.49 ± 151.90 Pa). Moreover, T(micro) contributes to improve the adhesion rate, expansion area and invasion depth of mTSCs. Further, T(micro) was highly expressed in tissue migration-related genes due to the activation of the Rho-associated coiled-coil containing protein kinase (ROCK) pathway at relatively similar modulus of trophoblast. Overall, our study explores the embryo implantation process with a new perspective, and provides theoretical support for understanding the effect of mechanics on embryo implantation.

Unsupervised cluster analysis reveals distinct subgroups in healthy population with different exercise responses of cardiorespiratory fitness.

Background: Considerable attention has been paid to interindividual differences in the cardiorespiratory fitness (CRF) response to exercise. However, the complex multifactorial nature of CRF response variability poses a significant challenge to our understanding of this issue. We aimed to explore whether unsupervised clustering can take advantage of large amounts of clinical data and identify latent subgroups with different CRF exercise responses within a healthy population. Methods: 252 healthy participants (99 men, 153 women; 36.8 ± 13.4 yr) completed moderate endurance training on 3 days/week for 4 months, with exercise intensity prescribed based on anaerobic threshold (AT). Detailed clinical measures, including resting vital signs, ECG, cardiorespiratory parameters, echocardiography, heart rate variability, spirometry and laboratory data, were obtained before and after the exercise intervention. Baseline phenotypic variables that were significantly correlated with CRF exercise response were identified and subjected to selection steps, leaving 10 minimally redundant variables, including age, BMI, maximal oxygen uptake (VO2max), maximal heart rate, VO2 at AT as a percentage of VO2max, minute ventilation at AT, interventricular septal thickness of end-systole, E velocity, root mean square of heart rate variability, and hematocrit. Agglomerative hierarchical clustering was performed on these variables to detect latent subgroups that may be associated with different CRF exercise responses. Results: Unsupervised clustering revealed two mutually exclusive groups with distinct baseline phenotypes and CRF exercise responses. The two groups differed markedly in baseline characteristics, initial fitness, echocardiographic measurements, laboratory values, and heart rate variability parameters. A significant improvement in CRF following the 16-week endurance training, expressed by the absolute change in VO2max, was observed only in one of the two groups (3.42 ± 0.4 vs 0.58 ± 0.65 ml⋅kg-1∙min-1, P = 0.002). Assuming a minimal clinically important difference of 3.5 ml⋅kg-1∙min-1 in VO2max, the proportion of population response was 56.1% and 13.9% for group 1 and group 2, respectively (P<0.001). Although group 1 exhibited no significant improvement in CRF at group level, a significant decrease in diastolic blood pressure (70.4 ± 7.8 vs 68.7 ± 7.2 mm Hg, P = 0.027) was observed. Conclusions: Unsupervised learning based on dense phenotypic characteristics identified meaningful subgroups within a healthy population with different CRF responses following standardized aerobic training. Our model could serve as a useful tool for clinicians to develop personalized exercise prescriptions and optimize training effects.

MiR-672-5p-Mediated Upregulation of REEP6 in Spinal Dorsal Horn Participates in Bortezomib-Induced Neuropathic Pain in Rats.

Evidence shows that miRNAs are deeply involved in nervous system diseases, but whether miRNAs contribute to the bortezomib (BTZ)-induced neuropathic pain remains unclear. We aimed to investigate whether miRNAs contribute to bortezomib (BTZ)-induced neuropathic pain and explore the related downstream cascades. The level of miRNAs in the spinal dorsal horn was explored using miRNA microarray and PCR. MiR-672-5p was significantly downregulated in dorsal horn neurons in the rats with BTZ treatment. Intrathecal injection of miR-672-5p agomir blunted the increase of the amplitude and frequency of sEPSCs in dorsal horn neurons and mechanical allodynia induced by BTZ. In addition, the knockdown of miR-672-5p by intrathecal injection of antagomir increased the amplitude and frequency of sEPSCs in dorsal horn neurons and decreased the mechanical withdrawal threshold in naïve rats. Furthermore, silico analysis and the data from subsequent assays indicated that REEP6, a potential miR-672-5p-regulating molecule, was increased in the spinal dorsal horn of rats with BTZ-induced neuropathic pain. Blocking REEP6 alleviated the mechanical pain behavior induced by BTZ, whereas overexpressing REEP6 induced pain hypersensitivity in naïve rats. Importantly, we further found that miR-672-5p was expressed in the REEP6-positive cells, and overexpression or knockdown of miR-672-5p reversely regulated the REEP6 expression. Bioinformatics analysis and double-luciferase reporter assay showed the existence of interaction sites between REEP6 mRNA and miR-672-5p. Overall, our study demonstrated that miR-672-5p directly regulated the expression of REEP6, which participated in the neuronal hyperexcitability in the spinal dorsal horn and neuropathic pain following BTZ treatment. This signaling pathway may potentially serve as a novel therapeutic avenue for chemotherapeutic-induced mechanical hypersensitivity.

Does vitamin D supplementation improve bone health, body composition and physical performance beyond endurance exercise in patients with type 2 diabetes: A secondary analysis of randomized controlled trial.

This study aimed to assess the effects of a 12-week vitamin D and endurance exercise intervention on bone health, body composition and physical performance among patients with type 2 diabetes. Totally, 61 patients were randomly assigned to vitamin D (VDG), exercise (EG), vitamin D and exercise intervention (VEG), and control (CG) groups. Bone health (bone mineral density, BMD; bone mineral content, BMC), body composition and physical performance were measured before and after the intervention. Dual energy X-ray absorptiometry was used to assess bone health and body composition. There were no additive effects of vitamin D beyond exercise were observed. Vitamin D supplementation had significant effects on maintaining bone health compared with their counterpart Total (BMC, EG + CG: 2,719.9 ± 70.0 vs. 2,670.1 ± 65.6; VDG + VEG: 2,610.9 ± 88.2 vs. 2,605.3 ± 84.8; trunk BMC, 870.2 ± 26.8 vs. 836.3 ± 23.7; 824.8 ± 29.5 vs. 822.1 ± 27.8; spine BMD, 1.15 ± 0.03 vs. 1.11 ± 0.02; 1.09 ± 0.03 vs. 1.09 ± 0.02) were observed. Exercise had a main effect on the reduction of total and trunk BF%. Patients in EG had a decreased BMC, while it was alleviated in VEG after intervention. Although no additive effect of vitamin D supplementation beyond exercise training, the supplementation had a potential effect on the prevention of bone loss induced by exercise only.

Mechanisms of exercise for diabetic neuropathic pain.

Diabetic neuropathic pain (DNP) is a common disease that affects the daily lives of diabetic patients, and its incidence rate is very high worldwide. At present, drug and exercise therapies are common treatments for DNP. Drug therapy has various side effects. In recent years, exercise therapy has received frequent research and increasing attention by many researchers. Currently, the treatment of DNP is generally symptomatic. We can better select the appropriate exercise prescription for DNP only by clarifying the exercise mechanism for its therapy. The unique pathological mechanism of DNP is still unclear and may be related to the pathological mechanism of diabetic neuropathy. In this study, the mechanisms of exercise therapy for DNP were reviewed to understand better the role of exercise therapy in treating DNP.

Exploration of bifunctional Vanadium-based Metal-Organic framework with double active centers for Potassium-ion batteries.

Exploration of suitable electrode hosts with large open channels that can reversibly accommodate K+ with large radius have been extensively investigated. Nevertheless, the reported inorganic counterparts were inevitably restricted by the difficulty of large K+ diffusion capability in crystal structure and the huge volume change. Herein, we report a bifunctional vanadium-based metal-organic framework (MIL-47) with double active centers and larger lamellar spacing that could serve as both cathode and anode material, respectively by controlling the redox potential range in potassium-ion batteries. The results suggest that the stable K-storage mechanism is the reversible rearrangement of the conjugated carboxyl groups of organic terephthalic acid into enolate and the reversible redox activity of V ions, with the specific capacity of 272 mAh g-1 (0.01-1.5 V) and 50 mAh g-1 (1.5-3.8 V) at the current density of 10 mA g-1 for MIL-47 anode and MIL-47 cathode, respectively. The unsaturated functional group of MIL-47 and the intermediate bridged V atom not only provide multi-dimensional channels for electron and ion transport but also stabilize its crystal structure. Additionally, a symmetric full-cell in potassium-ion batteries based on MIL-47 was constructed successfully by avoiding the utilization of K metal with safety concerns. Our results provide new insight into structure design for next-generation large-scale energy storage applications.

Comparison of the Diagnostic Accuracy of Percutaneous Fistula Contrast-Enhanced Ultrasound Combined with Transrectal 360° 3-D Imaging and Conventional Transrectal Ultrasound in Complex Anal Fistula.

This study compared the diagnostic accuracy of percutaneous fistula contrast-enhanced ultrasound (CEUS) combined with 360° 3-D transrectal ultrasound (TRUS) imaging (CEUS + 360°-TRUS) with that of conventional transrectal ultrasound in the diagnosis of complex anal fistulas. A total of 156 patients clinically diagnosed with complex anal fistula from January 2020 to December 2021 were studied and randomly divided into an experimental group (n = 82) and a control group (n = 74). Patients in the experimental group were examined by percutaneous fistula CEUS combined with CEUS + 360°-TRUS, while patients in the control group were examined using TRUS. The detection of fistulas (main tract, branch and internal orifice) and the accuracy of Parks classification were compared between the two groups. Recurrences were followed up at 1, 3 and 6 mo after the surgery. A total of 156 patients were included, aged 23-68 y (average: 37.7 ± 18.2 y). In both groups, the course of disease was <1 mo in 128 cases, 1-2 mo in 22 cases and >3 mo in 6 cases. A total of 474 fistulas were confirmed by surgery in the aforementioned patients, including 224 main fistulas, 250 branch pipes and 254 internal orifices. The CEUS + 360°-TRUS group had 96.87%, 90.41% and 90.14% diagnostic accuracy for the main tract, branch and internal orifice, which was statistically significant (p < 0.001) compared with the 85.00%, 70.00% and 72.46% for the TRUS group, respectively. The overall accuracy of Parks classification of anal fistula in the CEUS + 360°-TRUS group was significantly higher than that in the TRUS group (90.24% vs. 78.38%, p < 0.001). After 6 mo of follow-up, the recurrence rate in the CEUS + 360°-TRUS group was 4.87%, and the recurrence rate in the TRUS group was 18.91%. Percutaneous fistula CEUS combined with transrectal 360° 3-D imaging has significantly higher accuracy than conventional TRUS in the diagnosis of complex anal fistula, especially for anal fistula branches, internal openings and Parks classification and is beneficial in reducing post-operative occurrence of complex anal fistulas.

Modular Construction of Heterobiaryl Atropisomers and Axially Chiral Styrenes via All-Carbon Tetrasubstituted VQMs.

Here we report a new type of chiral all-carbon tetrasubstituted VQMs generated via chiral phosphoric acids catalyzed nucleophilic addition of 2-alkynylnaphthols to o-quinone methides or imines, which can be captured intramolecularly as a result of cycloaddition reaction. A new class of naphthyl-2H-chromenes bearing axially and centrally chiral elements and axially chiral quinone-naphthols were prepared efficiently with good to excellent yields, diastereoselectivities and enantioselectivities. Noteworthy, the enantioselective cycloaddition of alkynylnaphthols with o-quinone methides proceeded via a [2+2] cycloaddition, followed by a retro-4π-electrocyclization and a 6π re-cyclization. While the cycloaddition of alkynylnaphthols with imines proceeded via a sequential [2+4] cycloaddition and an auto oxidation reaction. Moreover, the obtained axially chiral naphthols can be converted into valuable phosphine ligands and other functional molecules.

Neuroimaging Assessment of Pain.

Pain is an unpleasant sensory and emotional experience. Understanding the neural mechanisms of acute and chronic pain and the brain changes affecting pain factors is important for finding pain treatment methods. The emergence and progress of non-invasive neuroimaging technology can help us better understand pain at the neural level. Recent developments in identifying brain-based biomarkers of pain through advances in advanced imaging can provide some foundations for predicting and detecting pain. For example, a neurologic pain signature (involving brain regions that receive nociceptive afferents) and a stimulus intensity-independent pain signature (involving brain regions that do not show increased activity in proportion to noxious stimulus intensity) were developed based on multivariate modeling to identify processes related to the pain experience. However, an accurate and comprehensive review of common neuroimaging techniques for evaluating pain is lacking. This paper reviews the mechanism, clinical application, reliability, strengths, and limitations of common neuroimaging techniques for assessing pain to promote our further understanding of pain.

A Dehydrogenative Inverse Electron Demand Diels-Alder Reaction for the Synthesis of Functionalized Pyranones.

An efficient dehydrogenative inverse electron demand Diels-Alder reaction of isopropyl and prenyl benzene derivatives with electron-deficient dienes followed by decarboxylation has been reported for the first time. The much broader substrate scope of dienophiles and electron-deficient dienes led to biologically valuable pyranones in good to excellent yields.

Single-Cell Analysis Reveals Transcriptomic Reprogramming in Aging Cardiovascular Endothelial Cells.

The senescence of cardiovascular endothelial cells (ECs) is a major risk factor in the development of aging-related cardiovascular diseases. However, the molecular dynamics in cardiovascular EC aging are poorly understood. Here, we characterized the transcriptomic landscape of cardiovascular ECs during aging and observed that ribosome biogenesis, inflammation, apoptosis and angiogenesis-related genes and pathways changed with age. We also highlighted the importance of collagen genes in the crosstalk between ECs and other cell types in cardiovascular aging. Moreover, transcriptional regulatory network analysis revealed Jun as a candidate transcription factor involved in murine cardiovascular senescence and we validated the upregulation of Jun in aged cardiovascular ECs both in vitro and in vivo. Altogether, our study reveals the transcriptomic reprogramming in the aging murine cardiovascular ECs, which deepens the understanding of the molecular mechanisms of cardiovascular aging and provides new insights into potential therapeutic targets against age-related cardiovascular diseases.

Scandium Triflate Catalyzed Tandem Transfer Hydrogenation and Cyclization Reaction of o-Aminobenzaldehydes and o-Aminoacetophenone with Alcohols.

An effective Sc-catalyzed transfer hydrogenation and cyclization tandem reaction has been achieved. This process showed excellent functional group compatibility and good yields. A variety of benzoxazines were produced with primary or secondary alcohols as a hydrogen source. Furthermore, the utility of this newly developed protocol is demonstrated through scaled-up experiment, late-stage modification, and preliminary exploration of enantioselective synthesis.

Organic 2,5-dihydroxy-1,4-benzoquinone potassium salt with ultrahigh initial coulombic efficiency for potassium-ion batteries.

Here, we propose a new organic 2,5-dihydroxy-1,4-benzoquinone potassium salt (K2C6H2O4) endowing an ultrahigh initial coulombic efficiency of 96% as an advanced anode for potassium-ion batteries. Theoretical calculations and experimental results suggest that K+ can reversibly insert into this organic compound due to the flexible and stable structure of the K2C6H2O4 molecule as well as fast K+ kinetics in the selected dimethyl ether-based electrolyte.

Selectfluor-Mediated Stereoselective [1 + 1 + 4 + 4] Dimerization of Styrylnaphthols.

Stereoselective [1 + 1 + 4 + 4] dimerization of 1-styrylnaphthols has been developed by using Selectfluor as the oxidant for the first time. The reaction was compatible with various functional groups, giving a class of ethanodinaphtho[b,f][1,5]dioxocines with novel 3D skeletons. DFT calculations indicate that this method merges an intriguing stereoselective intermolecular 1 + 1 radical coupling to construct a bridged C-C bond and then an intramolecular [4 + 4] formal cycloaddition of the in situ generated o-quinone methide intermediate.

Percutaneous contrast-enhanced ultrasound for localization and diagnosis of sentinel lymph node in early breast cancer.

This study assessed the efficacy of percutaneous contrast-enhanced ultrasound (CEUS) in localization sentinel lymph node (SLNs) for biopsy and diagnosis of metastatic SLNs in patients with early breast cancer. From January to November 2017, seventy-five patients with early breast cancer confirmed by pathology were enrolled in this study. CEUS was performed after subdermal injection of ultrasound contrast agent (SonoVue, 2.0 ml in total dose) around the areola on the ipsilateral side of the breast. The contrast-enhanced lymphatic vessels and associated SLNs were observed and traced in real time. The lymphatic vessels and SLN were mapped and labeled on the skin surface. Sentinel lymph node biopsy (SLNB) was performed after injection of 2.0 ml methylene blue at same injection site of SonoVue. The accuracy of percutaneous CEUS localization of SLNs was determined compared to blue dye injection technique. The pathological results under blue dye guided biopsy were used as the reference standard to calculate the sensitivity and specificity of CEUS for the diagnosis of SLNs. A total of 163 SLNs obtained through SLNB following methylene blue tracing in 75 patients. There were 116 SLNs identified by percutaneous CEUS. The difference of detection rates between blue dye and CEUS was statistically significant (Z = -2.651, P = 0.008). The identification rate of SLNs by CEUS was 71.17% (116/163). The accuracy of percutaneous CEUS localization of axillary SLNs was 94.67% (71/75) compared to blue dye-guided biopsy. Among the 116 SLNs detected by percutaneous CEUS, pathologic results showed 51 positive SLNs and 65 negative SLNs whiles CEUS findings indicated 83 positive SLNs and 33 negative SLNs. Only 50 of 83 SLNs had metastasis on pathology, while 33 were detected as false positive. The sensitivity and specificity of CEUS for the diagnosis of metastatic SLN was 98.04%(50/51) and 49.23%(32/65), respectively. Percutaneous CEUS can be used as an effective method to localize the SLNs for guiding SLNB. This method has excellent sensitivity for identifying the SLNs but lower specificity for detecting metastatic SLNs in patients with early stage breast cancer.

Palladium-Catalyzed Site-Selective C(sp3)-H Arylation of Phenylacetaldehydes.

We describe a Pd-catalyzed selective C-H arylation reaction of phenylacetaldehydes using l-valine as the transient directing group. This process showed a broad substrate scope and excellent selectivity in which a ligand-controlled functionalization of the unactivated ß-C(sp3)-H bond. In addition, enantioselective arylation of phenylacetaldehydes was preliminarily explored by utilizing a bulky chiral transient directing group.

Chiral Phosphoric-Acid-Catalyzed Cascade Prins Cyclization.

Asymmetric Prins cyclization of in situ generated quinone methides and o-aminobenzaldehyde has been developed with chiral phosphoric acid as an efficient catalyst. This unconventional method provides a facile access to diverse functionalized trans-fused pyrano-/furo-tetrahydroquinoline derivatives in excellent yield and with excellent diastereo- and enantioselectivities (up to 99% yield and 99% ee). Mechanistic studies suggested that the three adjacent tertiary stereocenters were constructed through the sequential formation of C-O, C-C, and C-N bonds.

Urinary markers in treatment monitoring of lung cancer patients with bone metastasis.

BACKGROUND: Bone metastasis remains critical for advanced stage non-small cell lung cancer (NSCLC)-a disease that is challenging to manage. Urinary markers present opportunities for non-invasive testing. METHODS: Urine specimens were collected from patients prior to treatment. Urinary cell-free DNA was subsequently purified from these samples. To address the specificity of the test, driver mutations in epidermal growth factor receptor L858R and L861Q were analyzed. Clinical specificity was established by comparison with healthy volunteers. Regular monitoring was established during treatment with tyrosine kinase inhibitors. The overall survival of patients was correlated with changes in circulating tumor DNA (ctDNA). RESULTS: Baseline clinical correlation of urinary ctDNA and matched tumor specimens achieved 89% concordance. The clinical specificity was 100%. The average background level of urinary ctDNA was 20.7 ng/mL. Comparing patients with and without bone metastasis, the latter had significantly lower baseline levels. During treatment, more pronounced decline in urinary ctDNA was observed in patients without bone metastasis. In our Kaplan-Meier estimator, we observed that patients with a more significant reduction in ctDNA had a better overall survival outcome. CONCLUSION: Our study demonstrates clear benefits and allows better risk profiling for NSCLC patients with bone metastasis. The non-invasive specimen collection is attractive and complements existing cancer management tools.

Prognostic value of mean platelet volume to plateletcrit ratio in patients with osteosarcoma.

OBJECTIVE: The objective of this study was to investigate the prognostic value of preoperative mean platelet volume to plateletcrit (MPV/PCT) ratio in patients with osteosarcoma. MATERIALS AND METHODS: The retrospective study included 188 consecutive osteosarcoma patients who experienced neoadjuvant chemotherapy and surgical resection of tumor. The relationships between MPV/PCT and clinicopathological characteristics were analyzed. The Kaplan-Meier analysis and Cox regression proportional hazard model were applied to assess the prognostic value of MPV/PCT ratio. RESULTS: MPV/PCT ratio was found to be significantly associated with platelet count, platelet distribution width, and PCT (all P<0.001). Kaplan-Meier analysis showed that high MPV/PCT ratio (≥43.58) was associated with a prolonged disease-free survival (DFS, P=0.035). The multivariate Cox revealed that only good chemotherapy response was an independent predictor of better DFS in the overall population. However, the stratification analysis showed that a high MPV/PCT ratio (≥43.58) was indicated as an independent prognostic factor for a favorable DFS (HR =0.137, 95%CI =0.029-0.644, P=0.012) in the male osteosarcoma patients but not in female patients. CONCLUSION: The high preoperative MPV/PCT ratio may serve as an independent prognostic factor for a favorable prognosis in male osteosarcoma patients. Further studies are needed to confirm the findings.