A bioinspired heterostructured nanochannel based on dendrimer-gold network and aluminum oxide arrays for sensitive detection of miRNA.

BACKGROUND: MicroRNAs, as oncogenes or tumor suppressors, enable to up or down-regulate gene expression during tumorigenesis. The detection of miRNAs with high sensitivity is crucial for the early diagnosis of cancer. Inspired by biological ion channels, artificial nanochannels are considered as an excellent biosensing platform with relatively high sensitivity and stability. The current nanochannel biosensors are mainly based on homogeneous membranes, and their monotonous structure and functionality limit its further development. Therefore, it is necessary to develop a heterostructured nanochannel with high ionic current rectification to achieve highly sensitive miRNA detection. RESULTS: In this work, an asymmetric heterostructured nanochannel constructed from dendrimer-gold nanoparticles network and anodic aluminum oxide are designed through an interfacial super-assembly method, which can regulate ion transport and achieve sensitive detection of target miRNA. The symmetry breaking is demonstrated to endow the heterostructured nanochannels with an outstanding ionic current rectification performance. Arising from the change of surface charges in the nanochannels triggered by DNA cascade signal amplification in solution, the proposed heterogeneous nanochannels exhibits excellent DNA-regulated ionic current response. Relying on the nucleic acid's hybridization and configuration transformation, the target miRNA-122 associated with liver cancer can be indirectly quantified with a detection limit of 1 fM and a wide dynamic range from 1 fM to 10 pM. The correlation fitting coefficient R2 of the calibration curve can reach to 0.996. The experimental results show that the method has a good recovery rate (98%-105 %) in synthetic samples. SIGNIFICANCE: This study reveals how the surface charge density of nanochannels regulate the ionic current response in the heterostructured nanochannels. The designed heterogeneous nanochannels not only possess high ionic current rectification property, but also enable to induce superior transport performance by the variation of surface chemistry. The proposed biosensor is promising for applications in early diagnosis of cancers, life science research, and single-entity electrochemical detection.

Retrograde percutaneous coronary intervention of chronic total occlusion via discontinuous septal channels.

OBJECTIVES: The study aims to investigate the safety and feasibility of retrograde CTO intervention via collateral connection grade 0 (CC-0) septal channel and to identify predictors of collateral tracking failure. BACKGROUND: Guidewire crossing a collateral channel is a critical step for successful retrograde percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). METHODS: Retrograde PCI was attempted in 122 cases of CTO with CC-0 septal collaterals from December 2018 to May 2021. A hydrophilic polymer coating guidewire was used for crossing all intended CC-0 collaterals. A multivariable logistic regression analysis was performed to identify the predictors of guidewire tracking failure via the CC-0 collaterals. RESULTS: Successful guidewire tracking via CC-0 septal channel was achieved in 98 (80.3%) of 122 cases. The independent predictors of CC-0 septal channel guidewire tracking failure included well-developed non-septal collateral (OR: 5.297, 95% CI: 1.107-25.353, p = 0.037) and the ratio length of posterior descending artery (PDA) versus the distance of PDA ostium to cardiac apex ≤2/3 (OR: 3.970, 95% CI: 1.454-10.835, p = 0.007). Collateral perforation, target vessel perforation, and cardiac tamponade occurred in 5 (4.1%), 3 (2.5%), and 6 (4.9%) cases, respectively. There were no complications requiring emergency cardiac surgery or revascularization of nontarget vessel. CONCLUSIONS: Retrograde PCI via CC-0 septal channels with a hydrophilic polymer-coated guidewire is feasible and safe in patients with CTO. Well-developed nonseptal collaterals and short PDA length influence the procedure success and the risk of guidewire tracking failure via CC-0 septal channels.

Ultrasound-Guided Transversus Abdominis Plane Block in Treating Abdominal Skin Tension Pain After Kyphosis Surgery: A Pilot Study in Enhanced Recovery After Surgery Setting.

BACKGROUND: The postsurgical management of patients with ankylosing spondylitis is often only focused on the incision pain, and the pain caused by abdominal skin traction is paid little attention. OBJECTIVES: To explore the effectiveness of ultrasound-guided transversus abdominis plane block (TAPB) in treating abdominal skin tension pain after kyphosis surgery. STUDY DESIGN: Randomized controlled trial. SETTING: This prospective study consecutively enrolled patients scheduled to undergo kyphosis correction surgery at the Department of Orthopedics of Xijing Hospital from March 2021 to December 2021. METHODS: The patients were randomized 1:1 to the TAPB and control groups. The Visual Analog Scale (VAS) for abdominal pain, Bruggrmann Comfort Scale (BCS), abdominal skin tension blisters, bed rest duration, length of hospitalization, and the use of patient-controlled analgesia pumps (PCAPs) were compared. The primary endpoint was pain alleviation at 24 hours after surgery. RESULTS: Thirty-one patients were enrolled, without differences between the 2 groups regarding age, body mass index, preoperative kyphosis severity, operation duration, and blood loss. The TAPB group (n = 16) had lower abdominal VAS scores than the control group (n = 15) at 2, 4, 6, 8, and 12 hours after surgery (P < 0.05). The TAPB group had higher BCS scores than the control group at 4, 6, 8, and 12 hours after surgery (P < 0.05). The TAPB group used PCAPs less frequently than the control group after surgery (P < 0.001). The incidence of tension blisters in the TAPB group was numerically lower than that of the control group, but the difference was not statistically significant (18.8% vs 33.3%, P > 0.05). LIMITATIONS: The sample size of this study is small and a single-center study, there might be data bias. CONCLUSIONS: In the first 24 hours after severe kyphosis surgery, TAPB can reduce the pain from abdominal skin tension and increase the comfort scores, but its effects on tension blisters remain to be further studied.

A microfluidic-based SERS biosensor with multifunctional nanosurface immobilized nanoparticles for sensitive detection of MicroRNA.

Developing sensitive and miniaturized biosensors for the detection of microRNAs (miRNAs) is highly desirable due to their association with early cancer diagnosis and prognosis. Here, a new microfluidic-based biosensor, combined with multifunctional nanosurface and DSN-assisted target recycle amplification strategy, is designed for the detection of miRNA-21. The design of nanosurface includes gold nanoparticles on porous anodic aluminum oxide (AAO) for surface enhanced Raman scattering (SERS) substrate, AuMBA@Ag core-shell nanoparticles for SERS nanotags and single-stranded DNA (ssDNA) in between for miRNA capture and nanotags immobilization. When the target miRNA is present near the nanosurface, it will be captured by ssDNA via hybridization reaction. Then, triggered by the DSN-assisted target recycle process, the freshly formed DNA/miRNA heteroduplexes are cleaved by DSN enzyme into DNA fragments and single-strand miRNA. The SERS nanotags are also dissociated from the nanosurface, leading to decrease of SERS signal. The cleaved target miRNA can be captured and SERS nanotags are released again in the next cycle, resulting in amplification of detection signal. To improve the accuracy of this biosensor, the functionalized AAO membrane is subdivided into two groups - AAO/Au array linked with encoded core-shell SERS nanotags acting as a reactor and primary detector and AAO/Au@Ag array serving as a collector and secondary detector for the dissociative SERS nanotags from the reactor. The decrease of SERS signal in primary detector and increase of signal in secondary detector ensures the accuracy and it is called dual-SERS detection strategy. The detection of miRNA-21 can be achieved with only 30 µL sample and 10 µL enzyme and a wide linear range of 10 fM∼10 nM is obtained. In addition, the microfluidic dual-SERS detection strategy can greatly reduce the possibility of false positive or false negative in single detection mode and it can be applied to the simultaneous detection of multiple miRNAs via integrating different probes.

Microencapsulation protects the biological activity of sea buckthorn seed oil.

Introduction: Sea buckthorn (Hippophae rhamnoides) seed oil is rich in unsaturated fatty acids, and is thus susceptible to oxidation and rancidity. Microencapsulation technology allows the effective protection of active substances, thereby prolonging the deterioration time and shelf life. Methods: In this study, H. rhamnoides microcapsules were prepared using a spray-drying method, and the microencapsulation parameters were optimized. The morphological characteristics, structural parameters, and stability of the microcapsules were determined using scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and oil oxidation stability testing. Results: Based on encapsulation efficiency (EE, %) and the particle size (D50) of the microcapsules, the optimal preparation conditions were characterized as a wall material consisting of soy protein isolate and soybean polysaccharide (2:3), a wall concentration of 15%, a core-to-wall ratio of 1:3, and an inlet temperature of 160°C. Under these optimal conditions, the encapsulation efficiency was 95.30 ± 2.67%, with a yield of 57.03 ± 3.71% and a particle size of 7.96 ± 1.04 µm. Discussion: Furthermore, the effectiveness of microencapsulation in protecting the biological activity of H. rhamnoides seed oil was confirmed by an antioxidation test. Thus, the results of this study showcase the successful microencapsulation of H. rhamnoides seed oil, thereby significantly improving its stability.

A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia.

To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells' cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100 % specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins.

Inhibition of microRNA-30a alleviates vascular remodeling in pulmonary arterial hypertension.

The excessive and ectopic pulmonary artery smooth muscle cells (PASMCs) are crucial to the pathogenesis of pulmonary arteriole (PA) remodeling in pulmonary arterial hypertension (PAH). We previously found that microRNA (miR)-30a was significantly increased in acute myocardial infarction (AMI) patients and animals, as well as in cultured cardiomyocytes after hypoxia, suggesting that it might be strongly associated with hypoxia-related diseases. Here, we investigated the role of miR-30a in the PASMC remodeling of PAH. The expression of miR-30a was higher in the serum of PAH patients compared with healthy controls. miR-30a was mainly expressed in PAs and was increased in PASMCs after hypoxia, mediating the downregulation of p53 tumor suppressor protein (P53). Genetic knockout of miR-30a effectively decreased right ventricular (RV) systolic pressure (RVSP), PA, and RV remodeling in the Su5416/hypoxia-induced and monocrotaline (MCT)-induced PAH animals. Additionally, pharmacological inhibition of miR-30a via intratracheal liquid instillation (IT-L) delivery strategy showed high efficiency, which downregulated miR-30a to mitigate disease phenotype in the Su5416/hypoxia-induced PAH animals, and these beneficial effects could be partially reduced by simultaneous P53 inhibition. We demonstrate that inhibition of miR-30a could ameliorate experimental PAH through the miR-30a/P53 signaling pathway, and the IT-L delivery strategy shows good therapeutic outcomes, providing a novel and promising approach for the treatment of PAH.

Rhythm outcomes after aortic valve surgery: Treatment and evolution of new-onset atrial fibrillation.

BACKGROUND: The impact of new-onset atrial fibrillation (AF) after aortic valve (AV) surgery on mid- and long-term outcomes is under debate. Here, we sought to follow up heart rhythms after AV surgery, and to evaluate the mid-term prognosis and effectiveness of treatment for patients with new-onset AF. METHODS: This single-center cohort study included 978 consecutive patients (median age, 59 years; male, 68.5%) who underwent surgical AV procedures between 2017 and 2018. All patients with postoperative new-onset AF were treated with Class III antiarrhythmic drugs with or without electrical cardioversion (rhythm control). Status of survival, stroke, and rhythm outcomes were collected and compared between patients with and without new-onset AF. RESULTS: New-onset AF was detected in 256 (26.2%) patients. For them, postoperative survival was comparable with those without new-onset AF (1-year: 96.1% vs. 99.3%; adjusted P = .30), but rate of stroke was significantly higher (1-year: 4.0% vs. 2.2%; adjusted P = .020). With rhythm control management, the 3-month and 1-year rates of paroxysmal or persistent AF between patients with and without new-onset AF were 5.1% versus 1.3% and 7.5% versus 2.1%, respectively (both P < .001). Multivariate models showed that advanced age, impaired ejection fraction, new-onset AF and discontinuation of beta-blockers were predictors of AF at 1 year. CONCLUSIONS: In most cases, new-onset AF after AV surgery could be effectively converted and suppressed by rhythm control therapy. Nevertheless, new-onset AF predisposed patients to higher risks of stroke and AF within 1 year, for whom prophylactic procedures and continuous beta-blockers could be beneficial.

Minimally Invasive Valve Replacement for Late Tricuspid Regurgitation After Left-Sided Valve Surgery.

Late severe tricuspid regurgitation after left-sided valve surgery can negatively affect long-term prognosis and quality of life. Because of extensive surgical trauma and poor right heart function, perioperative mortality after reoperation for tricuspid regurgitation historically remained high. A number of minimally invasive techniques were adopted at our center recently, including endoscopy-assisted right minithoracotomy, vacuum-assisted single femoral venous drainage without dissecting or snaring vena cava, direct right atriotomy through pericardium, and the beating-heart technique. Moreover, the tricuspid valves were replaced with bioprostheses in the majority of those patients at our center. The midterm outcomes of minimally invasive bioprosthetic tricuspid valve replacement were favorable.

Distal Remodeling After Operations for Extensive Acute Aortic Dissection.

BACKGROUND: The clinical predictors of distal aortic remodeling (DAR) after various procedures for extensive acute aortic dissection are not fully understood. METHODS: From 2008 to 2018, a total of 122 candidates with extensive acute type A and B aortic dissections survived operations of total arch replacement plus frozen elephant trunk (n = 36), ascending aortic replacement plus supraaortic debranching plus retrograde stenting (hybrid procedure; n = 25), and total endovascular repair (n = 61). We assessed DAR at 4 thoracoabdominal aortic levels based on true lumen expansion, false lumen patency, maximal aortic area, and the blood supply of major branches. Univariate and multivariate logistic and mixed-effect models were performed to delineate patterns and risks for DAR at midterm follow-up. RESULTS: At 3.9 years, 13 aorta-related adverse events (10.7%; including 3 aortic-related deaths [2.5%]) and 8 aortic reinterventions (6.6%) occurred. Follow-up computed tomography angiography was performed in all patients at 3.3 years (interquartile range, 2.7-4.4 years). The degree of DAR, which was relatively independent among aortic levels, was maximal at the pulmonary bifurcation level (90.2% complete false lumen thrombosis) and decreased along the distal aorta. Analyses of longitudinal data indicated that baseline overall false lumen patency was the only available factor to predict DAR at all 4 aortic levels. Dissection type, surgical technique, implant size, and medication did not sufficiently influence DAR at midterm follow-up. CONCLUSIONS: After distinct operations for extensive acute aortic dissection, DAR beyond the stent graft coverage is a local anatomical behavior independent of dissection type or proximal management.

Catastrophic health expenditures of households living with pediatric leukemia in China.

BACKGROUND: Leukemia can create a significant economic burden on the patients and their families. The objective of this study is to assess the medical expenditure and compensation of pediatric leukemia, and to explore the incidence and determinants of catastrophic health expenditure (CHE) among households with pediatric leukemia patients in China. METHODS: A cross-sectional interview was conducted among households living with pediatric leukemia using a questionnaire in two tertiary hospitals. CHE was defined as out-of-pocket (OOP) payments that were greater than or equal to 40% of a household's capacity to pay (CTP). Chi-square tests and logistic regression analysis were performed to identify the determinants of CHE. RESULTS: Among 242 households living with pediatric leukemia, the mean OOP payment for pediatric leukemia healthcare was $9860, which accounted for approximately 35.7% of the mean household's CTP. The overall incidence of CHE was 43.4% and showed a downward trend with the lowest income group at 69.0% to the highest income group at 16.1%. The logistic regression model found that medical insurance, frequency of hospital admissions, charity assistance, and income level were significant predictors of CHE. CONCLUSION: The results revealed that pediatric leukemia had a significant catastrophic effect on families, especially those with lower economic status. The occurrence of CHE in households living with pediatric leukemia could be reduced by addressing income disparity. In addition, extending coverage and improving compensation from medical insurance could also alleviate CHE. Some other measures that can be implemented are to address the barriers of charity assistance for vulnerable groups.

Isolated reoperation for tricuspid regurgitation after left-sided valve surgery: technique evolution.

OBJECTIVES: This study aimed to compare the isolated replacement and repair of severe tricuspid regurgitation after left-sided valve surgery (LSVS) and to report the evolution of this surgical technique. METHODS: From January 2005 to August 2018, 118 patients underwent isolated tricuspid valve replacement (iTVR, n = 93) or repair (iTVr, n = 25) for severe tricuspid regurgitation after LSVS. The surgical protocol at our institution has significantly changed since 2015, implementing the right thoracotomy approach (95.5%) and peripheral cannulation strategy with the vacuum-assist single venous drainage technique (93.2%) with a concomitant enhancement in preoperative right heart function optimization. Patients were followed up for 32.5 ± 34.6 (1.6-158.7) months. RESULTS: The operative mortality rate was 8.5% (8.6% in iTVR and 8.0% in iTVr, P = 0.924) with a significant decrease from 23.3% (2005-2014) to 3.4% (2015-2018) (P < 0.001), which was associated with preoperative New York Heart Association functional class IV [odds ratio (OR) 14.73, 95% confidence interval (CI) 2.68-80.90; P = 0.002] and anaemia (OR 6.60, 95% CI 1.03-42.22; P = 0.046). After adjusting the logistic regression model, the vacuum-assist single venous drainage technique was also associated with lower operative mortality and composite adverse outcomes. The overall 1- and 5-year survival rates were 91.5% (95% CI 84.8-95.3%) and 77.9% (95% CI 60.0-88.3%), respectively, and no difference was found between the iTVR and iTVr groups (P = 0.813). CONCLUSIONS: Isolated tricuspid valve reoperation for severe tricuspid regurgitation after LSVS is historically a high-risk procedure, but satisfactory results are achievable with advanced surgical techniques and improved perioperative management. Bioprosthetic iTVR is a reliable alternative for severe tricuspid regurgitation after LSVS.

Acute Commissural Rupture in a Giant Aortic Root Aneurysm.

Idiopathic rupture of aortic valve commissure is an extremely rare cause of acute aortic regurgitation. Here, we report a case of commissural rupture with giant root aneurysm and history of chronic aortic regurgitation, emphasizing the diagnostic value of high-quality three-dimensional reconstructions of multimodality imaging in assessing the cause of abruptly deteriorating valve regurgitation.

Continuous Beta-Blocker Therapy Delays Structural Deterioration after Bioprosthetic Mitral Valve Replacement.

The impact of continuous beta-blocker (BB) therapy on structural valve deterioration (SVD) after bioprosthetic mitral replacement was investigated. From 2000 to 2005, 138 such patients were propensity score matched in a 1:1 fashion (continuous BB therapy after surgery, n = 69; without BB therapy, n = 69). Median follow-up was 12.3 years. Cardiac mortality was comparable between patients with and without BB therapy (p = 0.13), while the 10-year freedom from SVD was significantly higher in patients with BB therapy (92.4 vs. 76.3%, p = 0.001). In conclusion, continuous BB therapy may be considered in patients after bioprosthetic mitral valve replacement to delay SVD and improve prosthetic durability.

Patient-prosthesis mismatch in mitral annuloplasty for degenerative mitral regurgitation: an ignored issue.

OBJECTIVES: Elevated postoperative transmitral gradient (TMG), partially induced by a small annuloplasty ring, is associated with late atrial fibrillation (AF) after mitral valve repair. Here, we aimed to provide the optimal cut-off of prosthetic ring size to reduce patient-prosthesis mismatch (PPM) after mitral annuloplasty. METHODS: From 2006 to 2017, 262 patients who underwent mitral valve repair for degenerative pathologies were retrospectively studied. The relationships of body surface area (BSA)-indexed prosthetic orifice area (POAi)-postoperative TMG and POAi-late AF were tested using regression curves and receiver operating characteristic curves, respectively. The optimal cut-off of POAi predictive of late AF was used to define PPM. Baseline and follow-up data of patients with and without PPM were compared in propensity score-matched cohorts. RESULTS: In-hospital mortality was 0. Late AF was observed in 9.2% (24/262) patients during a median follow-up of 3.8 years. An exponential model was best fitted based on the POAi-postoperative TMG relationship (P < 0.001). Using late AF as the dependent variable, the optimal cut-off for PPM was POAi ≤2.28 cm2/m2 (c-statistic 0.71; sensitivity 0.61; specificity 0.80; P < 0.001). PPM was identified in 113 (43.1%) patients. After propensity score matching, the estimated 5-year rate of late AF was significantly higher in PPM patients than in non-PPM patients (24% vs 5%; P < 0.001). CONCLUSIONS: Postoperative TMG increases significantly with a small POAi for full ring annuloplasty. A patient's BSA should be considered in addition to valvular dimensions during the selection of a proper ring size to reduce PPM-related AF.