MR Uniformity Ratio Estimates to Evaluate Ventricular Mechanical Dyssynchrony and Prognosis After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis.

BACKGROUND: Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI. RESULTS: We found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation. CONCLUSION: This study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair.

Three-Dimensional Location of the Facial Artery in Relation to the Nasolabial Fold in Asian People: A Cadaveric CTA Study.

BACKGROUND: Injection cosmetics have become popular in recent years. The nasolabial fold is one of the most important and dangerous regions in the midface, and its three-dimensional relationship with the facial artery remains unclear. METHODS: Fifty-two cadavers infused with lead oxide contrast medium via the external carotid arteries were scanned by computed tomography (CT). The three-dimensional model was reconstructed using Mimics and Origin software, and the relevant data were calculated using validated algorithms. RESULTS: There were three facial artery types according to its course in relation to the nasolabial fold. In the most common type, accounting for 83.7% of specimens, the facial artery evolves into an angular artery, with a horizontal distance between facial artery and nasolabial fold of - 1.90 ± 2.40, - 3.90 ± 2.95, - 5.18 ± 3.42, - 5.59 ± 3.53, - 5.59 ± 3.83, - 6.07 ± 4.10, - 6.92 ± 3.70, - 6.79 ± 3.37, - 4.52 ± 3.20, and - 2.76 ± 3.60 (mm) from the nasal ala to the oral commissure and a vertical distance of - 4.03 ± 2.56, - 3.27 ± 2.27, - 2.81 ± 2.57, - 2.1 ± 2.64, - 1.5 ± 3.32, - 0.71 ± 3.99, 0.92 ± 4.43, 0.4 ± 5.31, - 4.14 ± 5.14, - 7.05 ± 4.74 (mm). CONCLUSIONS: The facial artery is vulnerable to damage when injecting filler in the nasolabial fold. For the upper 1/3 of the nasolabial fold, the supraperiosteal layer is recommended for injection, while for the lower 2/3 of the nasolabial fold, the dermal layer along the nasolabial fold is recommended. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Morphological Aesthetics Assessment of the Predicted 3D Simulation Results and the Actual Results of Breast Augmentation.

BACKGROUND: Although three-dimensional (3D) simulations are becoming more common in preoperative breast augmentation planning, this does not necessarily imply that the simulated results are highly accurate. OBJECTIVES: We aimed to evaluate the accuracy of the 3D simulation technique by comparing the differences in breast morphology between the 3D prediction model and the actual results. METHODS: The simulation and actual postoperative results of 103 patients who underwent breast augmentation were analyzed retrospectively. Therefore, a 3D model was created, and the parameters of line spacing, nipple position, breast projection, surface area, and volume were evaluated. Furthermore, consider the difference in chest circumferences and breast volume. RESULTS: In comparison with the simulation results, the actual results had a mean increase in the nipple to the inframammary fold (N-IMF) of 0.3 cm (P < 0.05) and a mean increase in basal breast width (BW) of 0.3 cm (P < 0.001), a difference that was not statistically significant in patients with larger breast volumes. There was a significant difference in the mean upper and lower breast volume distribution between simulated and actual breasts (upper pole 52.9% vs. 49.2%, P < 0.05, and lower pole 47.1% vs. 50.8%, P < 0.001). However, it was not statistically significant in patients with larger chest circumferences. CONCLUSIONS: Our study shows that 3D simulation has uncertainties related to the patient's chest circumference and breast volume. Therefore, these two critical factors must be considered when using simulation assessment in preoperative planning. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical Relevance of the Variability of the Infraorbital Arterial Anatomy Evaluated by Three-Dimensional Computed Tomography.

BACKGROUND: Knowledge of the anatomy of the infraorbital artery (IOA) is crucial for the rejuvenation of the anterior medial aspect of the midface; however, studies adequately describing the anatomy of the IOA branches are lacking, and their connection with the ophthalmic artery branches remains unclear. OBJECTIVES: This study aims to elucidate the anatomical characteristics of the IOA in its deployment within the lower eyelid using three-dimensional (3D) technology, thereby offering an anatomical foundation for clinical surgical procedures. METHODS: An analysis was conducted on computed tomography scans of 132 cadaveric head sides post-contrast injection, utilizing the Mimics software for reconstruction. The study focused on examining the anastomosis of the IOA, its principal branches, and the branches emanating from the ophthalmic artery. RESULTS: The prevalence of type I IOA was observed at 38.6% (51/132), while Type II IOA was found in 61.4% (81/132) of cases. A 7.6% incidence (10/132) of IOA directly anastomosing with the angular artery was noted. The presence of palpebral branches (PIOA) was identified in 57.6% (76/132) of instances. In the lower eyelid, four distinct distribution patterns of IOA were discerned: The likelihood of Type I PIOA was 5.3%, whereas for Types IIA, IIB, and IIC PIOA, the probabilities were 8.3%, 32.6%, and 11.4%, respectively. The occurrence of the orbital branch of IOA was recorded at 41.7% (55/132). CONCLUSIONS: 3D technology can map IOA variants and identify the deployment patterns of IOA branches in the lower eyelid vascular vesicles at high resolution as a guide in clinical practice. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Safety of Injections in the Infraorbital Region.

BACKGROUND:  Infraorbital filler injection is a commonly used minimally invasive cosmetic procedure on the face, which can cause vascular complications. OBJECTIVE:  In this study, we aimed to explore the anatomical structure of the infraorbital vasculature and to establish an accurate protocol for infraorbital filler injection. METHODS:  The vascular structure of the infraorbital region was evaluated in 84 hemifacial specimens using computed tomography. Four segments (P1-P4) and five sections (C1-C5) were considered. We recorded the number of identified arteries in each slice and at each location and the number of deep arteries. Furthermore, we also measured the infraorbital artery (IOA) distribution. RESULTS:  At P1-P4, the lowest number of arteries was detected in segment P4, with a 317/1727 (18.4%) and 65/338 (2.3%) probability of total and deep arterial identification, respectively. The probabilities of encountering an identified artery at the five designated locations (C1-C5) were 277/1727 (16%), 318/1727 (18.4%), 410/1727 (23.7%), 397/1727 (23%), and 325/1727 (18.8%), respectively. The probability of an IOA being identified at C2 was 68/84 (81%). CONCLUSION:  We described an effective filler injection technique in the infraorbital region to minimize the associated risks. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Famotidine Enhances Rifampicin Activity against Acinetobacter baumannii by Affecting OmpA.

The development of novel antibiotic adjuvants is imminent because of the frequent emergence of resistance in Gram-negative bacteria, which severely restricts the efficiency and longevity of commonly used clinical antibiotics. It is reported that famotidine, a clinical inhibitor of gastric acid secretion, enhances the antibacterial activity of rifamycin antibiotics, especially rifampicin, against Gram-negative bacteria and reverses drug resistance. Studies have shown that famotidine disrupts the cell membrane of Acinetobacter baumannii and inhibits the expression of the outer membrane protein ompA gene, while causing a dissipation of the plasma membrane potential, compensatively upregulating the pH gradient and ultimately increasing the accumulation of reactive oxygen species by leading to increased bacterial mortality. In addition, famotidine also inhibited the efflux pump activity and the biofilm formation of A. baumannii. In the Galleria mellonella and mouse infection models, the combination of famotidine and rifampicin increased the survival rate of infected animals and decreased the bacterial load in mouse organs. In conclusion, famotidine has the potential to be a novel rifampicin adjuvant, providing a new option for the treatment of clinical Gram-negative bacterial infections. IMPORTANCE In this study, famotidine was discovered for the first time to have potential as an antibiotic adjuvant, enhancing the antibacterial activity of rifamycin antibiotics against A. baumannii and overcoming the limitations of drug therapy. With the discovery of novel applications for the guanidine-containing medication famotidine, the viability of screening prospective antibiotic adjuvants from guanidine-based molecules was further explored. In addition, famotidine exerts activity by affecting the OmpA protein of the cell membrane, indicating that this protein might be used as a therapeutic drug target to treat A. baumannii infections.

An Integrated Algorithm for Differentiating Hypertrophic Cardiomyopathy From Hypertensive Heart Disease.

BACKGROUND: Differentiating hypertrophic cardiomyopathy (HCM) from hypertensive heart disease (HHD) is challenging. PURPOSE: To identify differences between HCM and HHD on a patient basis using MRI. STUDY TYPE: Retrospective. POPULATION: A total of 219 subjects, 148 in phase I (baseline data and algorithm development: 75 HCM, 33 HHD, and 40 controls) and 71 in phase II (algorithm validation: 56 HCM and 15 HHD). FIELD STRENGTH/SEQUENCE: Contrast-enhanced inversion-prepared gradient echo and cine-balanced steady-state free precession sequences at 3.0 T. ASSESSMENT: MRI parameters assessed included left ventricular (LV) ejection fraction (LVEF), LV end systolic and end diastolic volumes (LVESV and LVEDV), mean maximum LV wall thickness (MLVWT), LV global longitudinal and circumferential strain (GRS, GLS, and GCS), and native T1. Parameters, which were significantly different between HCM and HHD in univariable analysis, were entered into a principal component analysis (PCA). The selected components were then introduced into a multivariable regression analysis to model an integrated algorithm (IntA) for screening the two disorders. IntA performance was assessed for patients with and without LGE in phase I (development) and phase II (validation). STATISTICAL TESTS: Univariable regression, PCA, receiver operating curve (ROC) analysis. A P value <0.05 was considered statistically significant. RESULTS: Derived IntA formulation included LVEF, LVESV, LVEDV, MLVWT, and GCS. In LGE-positive subjects in phase l, the cutoff point of IntA ≥81 indicated HCM (83% sensitivity and 91% specificity), with the area under the ROC curve (AUC) of 0.900. In LGE-negative subjects, a higher possibility of HCM was indicated by a cutoff point of IntA ≥84 (100% sensitivity and 82% specificity), with an AUC of 0.947. Validation of IntA in phase II resulted in an AUC of 0.846 in LGE-negative subjects and 0.857 in LGE-positive subjects. DATA CONCLUSION: A per-patient-based IntA algorithm for differentiating HCM and HHD was generated from MRI data and incorporated FT, LGE and morphologic parameters. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Immunization effect of recombinant Lactobacillus casei displaying Aeromonas veronii Aha1 with an LTB adjuvant in carp.

Aeromonas veronii is an important aquatic zoonotic, which elicits a range of diseases, such as haemorrhagic septicemia. To develop an effective oral vaccine against Aeromonas veronii infection in carp, the Aeromonas veronii adhesion (Aha1) gene was used as a target molecule to attach to intestinal epithelial cells. Two anchored recombinant. Lactic acid bacteria strains (LC-pPG-Aha1 1038 bp and LC-pPG-Aha1-LTB 1383 bp) were constructed by fusing them with the E. coli intolerant enterotoxin B subunit (LTB) gene and using Lactobacillus casei as antigen delivery vector to evaluate immune effects of these in carp. Western blotting and immunofluorescence were used to confirm that protein expression was successful. Additionally, levels of specific IgM in serum and the activities of ACP, AKP, SOD, LYS, C3, C4, and lectin enzymes-were assessed. Cytokines IL-10, IL-1ß, TNF-α, IgZ1, and IgZ2 were measured in the liver, spleen, kidney, intestines, and gills tissue by qRT-PCR, which showed an increasing trend compared with the control group (P < 0.05). A colonization assay showed that the two L. casei recombinants colonized the middle and hind intestines of immunized fish. When immunized carp were experimentally challenged with Aeromonas veronii the relative percentage protection of LC-pPG-Aha1 was 53.57%, and LC-pPG-Aha1-LTB was 60.71%. In conclusion, these results demonstrate that Aha1 is a promising candidate antigen when it is displayed on lactic acid bacteria (Lc-pPG-Aha1 and Lc-pPG-Aha1-LTB) seems promising for a mucosal therapeutic approach. We plan to investigate the molecular mechanism of the L. casei recombinant in regulating the intestinal tissue of carp in future studies.

Antimicrobial resistance in E. Coli of animal origin and discovery of a novel ICE mobile element in Northeast China.

BACKGROUND: Multidrug resistance in Enterobacteriaceae including resistance to quinolones is rising worldwide. The development of resistance may lead to the emergence of new transmission mechanisms. In this study, the collection of different E. coli was performed from animals and subjected to subsequent procedures including pulsed-field gel electrophoresis, micro-broth dilution method, polymerase chain reaction. Whole genome sequencing of E. coli C3 was performed to detect the affinity, antimicrobial resistance and major carriers of the isolates. RESULTS: A total of 66 E. coli were isolated and their antibiotic resistance genes, frequency of horizontal transfer and genetic environment of E. coli C3 were determined. The results showed there were both different and same types in PFGE typing, indicating clonal transmission of E. coli among different animals. The detection of antimicrobial resistance and major antibiotic resistance genes and the plasmid transfer results showed that strains from different sources had high levels of resistance to commonly used clinical antibiotics and could be spread horizontally. Whole-genome sequencing discovered a novel ICE mobile element. CONCLUSION: In summary, the antimicrobial resistance of E. coli in northeast China is a serious issue and there is a risk of antimicrobial resistance transmission. Meanwhile, a novel ICE mobile element appeared in the process of antimicrobial resistance formation.

Physical therapy for end-stage hemophilic arthropathy: a case report.

This report introduces a young adult who has been in bed for more than ten years with end-stage hemophilic arthropathy. He didn't have access to factor VIII (FVIII) in the early stage of hemophilia due to the high costs of clotting replacement therapy. As a result, he is experiencing some difficulties, such as joint contracture, muscular atrophy, severe pain, and poor function of cardiopulmonary. He came to visit us for a comprehensive rehabilitation program, and, finally, he achieved the basic goal of self-care in daily life.

Percutaneous transluminal angioplasty for radial artery graft stenosis after high-flow superficial temporal artery trunk to middle cerebral artery interposition bypass.

Due to its higher patency rate, a radial artery graft (RAG) is used as an interposition graft for internal-external high-flow bypass more frequently than a saphenous vein graft (SAG). Nevertheless, there are still a few cases of RAG stenosis after bypass surgery. Unfortunately, these reports do not elaborate on the treatment for RAG stenosis. Here, we report the first case of severe RAG stenosis after high-flow STAt-RA-MCA bypass, which was successfully treated with PTA. We speculated that RAG stenosis is associated with the over-length and kinking of the intracranial segment of the RAG instead of vasospasm. We elaborated on the surgical procedure and treatment experience in this particular case in detail. According to our experience, PTA is a type of surgical procedure that can be considered for treating RAG stenosis after high-flow bypass. As long as the surgical procedure can be performed well according to the distance between the stenosis and the anastomosis and the characteristics of the RA tissue, PTA is able to achieve satisfactory long-term results.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress.

Antibiotic tolerance has become an increasingly serious crisis that has seriously threatened global public health. However, little is known about the exogenous factors that can trigger the development of antibiotic tolerance, both in vivo and in vitro. Herein, we found that the addition of citric acid, which is used in many fields, obviously weakened the bactericidal activity of antibiotics against various bacterial pathogens. This mechanistic study shows that citric acid activated the glyoxylate cycle by inhibiting ATP production in bacteria, reduced cell respiration levels, and inhibited the bacterial tricarboxylic acid cycle (TCA cycle). In addition, citric acid reduced the oxidative stress ability of bacteria, which led to an imbalance in the bacterial oxidation-antioxidant system. These effects together induced the bacteria to produce antibiotic tolerance. Surprisingly, the addition of succinic acid and xanthine could reverse the antibiotic tolerance induced by citric acid in vitro and in animal infection models. In conclusion, these findings provide new insights into the potential risks of citric acid usage and the relationship between antibiotic tolerance and bacterial metabolism.

Catheter Ablation of a Right Atrial Free Wall Diverticulum-Related Accessory Pathway Masquerading as a Septal One.

Epicardial right-sided accessory pathway (AP) ablation is challenging. In rare cases, the atrial insertion of the AP is related to unconventional sites and associated with repeated and complex ablation procedures. In this study, we report a case of right free wall diverticulum-related AP with a distinct surface electrocardiogram (ECG).A 45-year-old male patient with repetitive palpitation for 2 years was referred for an electrophysiological (EP) study. His resting surface ECG showed manifest ventricular preexcitation with a negative delta wave and a "QS" wave in precordial lead V1, which is most consistent with right mid-septal AP.In the EP study, orthodromic atrioventricular reentrant tachycardia could be easily induced with the earliest atrial activation at the right atrium (RA) free wall, but the AP failed to be blocked by ablating the earliest activation on the tricuspid annulus edge. An epicardial free wall AP was then suspected.Inadvertent catheter manipulation into a narrow and long chamber was noted on the RA geometry. Angiography via contrast injection from the ablation tip revealed a diverticulum extending from the RA to the right ventricle side. The epicardial AP was suspected to be related to this diverticulum. The earliest atrial activation, as shown through a detailed activation mapping, was located at the entrance of the diverticulum. Subsequent ablation at the atrial insertion site successfully abolished the antegrade and retrograde AP conduction without any complication. A postprocedural computed tomography scan proved the presence of a free wall diverticulum associated with the right atrial appendage.A diverticulum-related AP at RA free wall might exhibit surface ECGs mimicking that of an AP at the RA septum. The approach targeting the atrial insertion of the epicardial AP is effective and might be facilitated by clarification of structural malformations prior to the ablation procedure.

Phoenixin-14 alleviates inflammatory smooth muscle cell-induced endothelial cell dysfunction in vitro.

BACKGROUND: Intracranial aneurysm (IA) is cerebrovascular disorder which refers to local vessel wall damage to intracranial arteries, forming abnormal bulge. Both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are closely associated with IA formation and rupture. Inflammatory SMCs (iSMCs) were reported to induce EC dysfunction and result in IA progression. Phoenixin-14 (PNX-14) is a recently discovered brain peptide with pleiotropic roles, which participates in reproduction, cardio protection, lipid deposition and blood glucose metabolism. PNX-14 was previously reported to protect brain endothelial cells against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell injury. Therefore, our study was designed to investigate the influence of PNX-14 on iSMCs-induced endothelial dysfunction. METHODS: Inflammation in SMCs was induced by cyclic mechanical stretch. Human umbilical vein endothelial cells (HUVECs) were exposed to SMC- or iSMC-conditioned medium and then treated with 100 nM PNX-14 for 24 h. The levels of proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) in cell supernatants were analyzed by ELISA. Cell viability, apoptosis, angiogenesis and migration were subjected to CCK-8 assay, flow cytometry analysis, tube formation assay and Transwell migration assay. The protein levels of proinflammatory cytokines and apoptosis markers (Bcl-2 and Bax) were evaluated by western blotting. RESULTS: Cyclic mechanical stretch upregulated IL-1ß, IL-6 and TNF-α levels in SMCs. Treatment with SMC- or iSMC-conditioned medium HUVECs inhibited cell viability, angiogenesis and migration and induced apoptosis in HUVECs. iSMC-conditioned medium has more significant effects on cell functions. However, the influence of SMC- or iSMC-conditioned medium treatment on HUVEC biological functions were reversed by PNX-14 treatment. PNX-14 exerts no significant influence on the biological functions of HUVECs treated with SMC medium. CONCLUSION: PNX-14 alleviates iSMCs-induced endothelial cell dysfunction in vitro.

Isolation and partial characterization of a novel bacteriocin from Pseudomonas azotoformans with antimicrobial activity against Pasterella multocida.

In this study, a bacteriocin PA996 isolated from Pseudomonas azotoformans (P. azotoformans) was purified to homogeneity by ammonium sulphate precipitation and SP-Sepharose column chromatography. P. azotoformans began to grow at 6 h, reached exponential phase at 12-18 h. Bacteriocin PA996 was produced at 18 h and reached a maximum level of 2400 AU/mL. The molecular mass of purified bacteriocin PA996 was estimated by SDS-PAGE and its molecular mass was approximately 50 kDa. By screening in vitro, the bacteriocin PA996 showed an antimicrobial activity against Pasteurella multocida (P. multocida). The bacteriocin PA996 showed antibacterial activity in the range of pH2-10 and it was heat labile. The inhibitory activities were diminished after treatment with proteinase K, trypsin and papain, respectively, while catalase treatment was ineffective. The minimal inhibitory concentration (MIC) and bactericidal kinetics curves showed that the bacteriocin PA996 had a good inhibitory ability against P. multocida. Our data indicate that bacteriocin PA996 could inhibit the growth of P. maltocida and it may have the potential to apply as an alternative therapeutic drug.

Multimodal Recanalization for Subacute Symptomatic Internal Carotid Artery Occlusion Due to Atherosclerosis: Outcomes and Notes on Hybrid Techniques.

BACKGROUND: Subacute internal carotid artery occlusion (ICAO) is associated with ipsilateral recurrent stroke, and successful recanalization of ICAO can improve cerebral blood perfusion (CBP) and prevent stroke. However, the optimal treatment remains controversial. METHODS: We conducted a retrospective analysis of patients with subacute symptomatic ICAO due to atherosclerosis treated at our center. The hybrid surgical procedures included carotid endarterectomy, Fogarty balloon catheter embolectomy, aspiration thrombectomy, and percutaneous transluminal angioplasty/stenting. Recanalization rates, CBP improvement, stroke recurrence, and restenosis/reocclusion were investigated. RESULTS: Fourteen symptomatic atherosclerotic ICAO patients (type A, 4; type C, 10; men, 11; women, 3; average age, 68.1 ± 7.9 years) in the subacute phase were treated with a multimodal recanalization technique. Symptoms included mild cerebral infarction, transient ischemic attack (TIA), and amaurosis fugax. The average onset-to-treatment time was 18.1 ± 4.8 days. The successful recanalization (thrombolysis in cerebral ischemia grade 2 or 3) rate was 100%. The ipsilateral-to-contralateral mean transit time ratio was significantly lower at the 1-year follow-up than preoperatively (1.01 ± 0.05 vs. 1.26 ± 0.09, P < 0.0001). There was one case of restenosis detected 1 year after surgery and no cases of reocclusion. During the 28.3 ± 10.0 months of follow-up, only two cases of TIA occurred. The average modified Rankin Scale score and National Institute of Health Stroke Scale score were significantly lower at the most recent follow-up than before recanalization (1.21 ± 0.89 vs. 1.86 ± 0.66, P = 0.0003; 1.36 ± 1.55 vs. 2.00 ± 1.88, P = 0.0066). CONCLUSIONS: Multimodal recanalization techniques performed in a hybrid operation theater can safely achieve high recanalization rates in atherosclerotic ICAO patients in the subacute phase, which can be beneficial for recovering CBP and preventing stroke.

Recurrent hypoglycemic coma and diabetic ketoacidosis caused by insulin antibody. A rare case of type 1 diabetes mellitus.

Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: < 5%), and the concentrations of insulin and C-peptide were > 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.

Macro-reentrant atrial tachycardia after tricuspid or mitral valve surgery: is there difference in electrophysiological characteristics and effectiveness of catheter ablation?

BACKGROUND: Macro-reentrant atrial tachycardias (MATs) are a common complication after cardiac valve surgery. The MAT types and the effectiveness of MAT ablation might differ after different valve surgery. Data comparing the electrophysiological characteristics and the ablation results of MAT post-tricuspid or mitral valve surgery are limited. METHODS: Forty-eight patients (29 males, age 56.1 ± 13.3 years) with MAT after valve surgery were assigned to tricuspid valve (TV) group (n = 18) and mitral valve (MV) group (n = 30). MATs were mapped and ablated guided by a three-dimensional navigation system. The one-year clinical effectiveness was compared in two groups. RESULTS: Nineteen MATs were documented in TV group, including 16 cavo-tricuspid isthmus (CTI)-dependent AFL and 3 other MATs at right atrial (RA) free wall, RA septum and left atrial (LA) roof. Thirty-nine MATs were identified in MV group, including15 CTI-dependent AFL, 8 RA free wall scar-related, 2 RA septum scar-related, 8 peri-mitral flutter, 3 LA roof-dependent, 2 LA anterior scar-related, and 1 right pulmonary vein-related MAT. Compared with TV group, MV group had significantly lower prevalence of CTI-dependent AFL (38.5% vs. 84.2%), higher prevalence of left atrial MAT (35.9 vs.5.3%) and higher proportion of patients with left atrial MAT (40 vs. 5.6%), P = 0.02, 0.01 and 0.01, respectively. The acute success rate of MAT ablation (100 vs. 93.3%) and the one-year freedom from atrial tachy-arrhythmias (72.2 vs. 76.5%) was comparable in TV and MV group. No predictor for recurrence was identified. CONCLUSION: Although the types of MATs differed significantly in patients with prior TV or MV surgery, the acute and mid-term effectiveness of MAT ablation was comparable in two groups. TRIAL REGISTRATION: This study was registered as a part of EARLY-MYO-AF clinical trial at the website ClinicalTrials. gov (NCT04512222).