Synergistic effects of multidrug/material combination deliver system for anti-mutidrug-resistant tumor.

Multidrug resistance (MDR) is a public health issue of particular concern, for which nanotechnology-based multidrug delivery systems are considered among the most effective suppressive strategies for such resistance in tumors. However, for such strategies to be viable, the notable shortcomings of reduced loading efficiency and uncontrollable drug release ratio need to be addressed. To this end, we developed a novel "multidrug/material" co-delivery system, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, P-gp efflux pump inhibitor) and poly(amidoamine) (PAMAM) to fabricate a precursor material with the properties of reversing MDR and having a long-cycle. Further, to facilitate multidrug co-delivery, we loaded doxorubicin(Dox) and curcumin(Cur, cardiotoxicity modifier and P-gp inhibitor) into PAMAM-TPGS nano-micelles respectively, and mixed in appropriate proportions. The multidrug/material co-delivery system thus obtained was characterized by high drug loading and a controllable drug release ratio in the physiological environment. More importantly, in vitro and in vivo pharmacodynamic studies indicated that the multidrug/material co-delivery system facilitated the reversal of MDR. Moreover, the system has increased anti-tumor activity and is biologically safe. We accordingly propose that the "multidrug/material" co-delivery system developed in this study could serve as a potential platform for reversing MDR and achieving safe and effective clinical treatment.

Targeted drug delivery systems for matrix metalloproteinase-responsive anoparticles in tumor cells: A review.

Nanodrug delivery systems based on tumor microenvironment responses have shown excellent performance in tumor-targeted therapy, given their unique targeting and drug-release characteristics. Matrix metalloproteinases (MMPs) have been widely explored owing to their high specificity and expression in various tumor microenvironments. The design of an enzyme-sensitive nanodelivery system using MMPs as targeted receptors could markedly improve the performance of drug targeting. The current review focuses on the development and application of MMP-responsive drug carriers, and summarizes the classification of single- and multi-target nanocarriers based on their MMP responsiveness. The potential applications and challenges of this nanodrug delivery system are discussed to provide a reference for designing high-performance nanodrug delivery systems.

Strategy and technique for surgical treatment of Ebstein's anomaly.

BACKGROUND: Ebstein's anomaly (EA) is a rare and complex congenital heart anomaly, and the effect of surgical treatment is not ideal. This study aims to introduce our experience in management strategies, surgical techniques, and operative indications for patients with Ebstein's anomaly. METHODS: A retrospective study of 258 operations was performed in 253 patients by the same cardiac surgeon in The First Hospital of Tsinghua University between March 2004 and January 2020. 32 patients had previously received cardiac surgery in other hospitals. The clinical data including diagnosis, operative indications, techniques, pathological changes, and survival rates were collected and analyzed. RESULTS: Anatomical correction was performed in 203 (78.7%) operations, 1½ ventricle repair in 38 (14.7%) operations, tricuspid valve repair only in four operations (1.6%), tricuspid valve replacement in ten (3.9%), total cavopulmonary connection (TCPC) in two (0.8%), and Glenn operation in one operation (0.4%). Reoperation was performed in five patients (2.0%) during hospitalization. Among them, tricuspid valve replacement was performed in one patient, 1½ ventricle repair in two patients, and tricuspid valve annulus reinforcement in two patients. Five patients died with an early mortality rate of 2.0%. Complete atrioventricular conduction block was complicated in one patient (0.4%). A total of 244 patients was followed up (four in the 253 patients lost) with a duration of 3.0-168.0 (87.6 ± 38.4) months. Cardiac function of 244 patients improved significantly with mean New York Heart Association (NYHA) functional class recovery from 3.5 to 1.1. The mean grade of tricuspid valve regurgitation improved from 3.6 to 1.5. Three late deaths (1.2%) occurred. The survival rates at five and ten years after surgery were 98.6% and 98.2%, respectively. Reoperation was performed in five patients (2.0%) during the follow-up period. CONCLUSION: Based on our management strategies and operative principles and techniques, anatomical correction of EA is capable of achieving excellent long-term results, and low rates of TCPC, 1½ ventricle repair and valvular replacement.

Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature - The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11).

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Strain and Strain Rate To Evaluate Right Heart Function of Ebstein Anomaly (EA) Patients Before and After Operation.

OBJECTIVE: This study was aimed to elucidate the feasibility of using right ventricular (RV) strain and strain rate to evaluate right heart function of Ebstein anomaly (EA) patients before and after operation. METHODS: Sixty EA patients and 30 healthy controls underwent echocardiography (UCG) for evaluation of right heart function. Preoperative UCG and 1-week and 3-month postoperative UCG were performed in EA patients. RV strain and strain rate were measured on the four-chamber section of tissue Doppler imaging (TDI). RESULTS: The strain and strain rate representative of right ventricle systolic function were reduced prior to operation. RV strain and strain rate improved after the operation (P < .001), most significantly in the basal segment and middle segment of the free wall of the right ventricle as well as the basal segment of the interventricular septum (P < .001). CONCLUSIONS: The measurement of RV strain and strain rate on tissue Doppler imaging can be employed to assess the preoperative and postoperative RV function, proves the positive effect of tricuspid valve repair on right heart function, and offers more insight on right heart function evaluation.

Classification of Ventricular Septal Defects for the Eleventh Iteration of the International Classification of Diseases-Striving for Consensus: A Report From the International Society for Nomenclature of Paediatric and Congenital Heart Disease.

The definition and classification of ventricular septal defects have been fraught with controversy. The International Society for Nomenclature of Paediatric and Congenital Heart Disease is a group of international specialists in pediatric cardiology, cardiac surgery, cardiac morphology, and cardiac pathology that has met annually for the past 9 years in an effort to unify by consensus the divergent approaches to describe ventricular septal defects. These efforts have culminated in acceptance of the classification system by the World Health Organization into the 11th Iteration of the International Classification of Diseases. The scheme to categorize a ventricular septal defect uses both its location and the structures along its borders, thereby bridging the two most popular and disparate classification approaches and providing a common language for describing each phenotype. Although the first-order terms are based on the geographic categories of central perimembranous, inlet, trabecular muscular, and outlet defects, inlet and outlet defects are further characterized by descriptors that incorporate the borders of the defect, namely the perimembranous, muscular, and juxta-arterial types. The Society recognizes that it is equally valid to classify these defects by geography or borders, so the emphasis in this system is on the second-order terms that incorporate both geography and borders to describe each phenotype. The unified terminology should help the medical community describe with better precision all types of ventricular septal defects.

Intraoperative Transesophageal Echocardiography in the Operation of Ebstein's Anomaly: A Retrospective Study.

BACKGROUND: Ebstein's anomaly (EA) has various spectrums in clinical and anatomic features. This study aimed to report the experience of two-dimensional intraoperative transesophageal echocardiography (2D-ITEE) during the EA surgery and to analyze the characteristics of the tricuspid valve (TV) by comparing the data from 2D-ITEE with the results from the surgery. METHODS: 2D-ITEE data of 164 patients with EA who were operated in the First Hospital of Tsinghua University between July 2004 and April 2014 were retrospectively analyzed in this study. 2D-ITEE was applied in all patients. Downward displacement distances were measured, and the numbers of downward displacement or absent leaflets were compared with that of the surgery and with that of the two-dimensional-transthoracic echocardiogram (2D-TTE). Data comparison was performed using the Chi-square test. RESULTS: The anterior leaflet partial or total downward displacement was 37.76 ± 17.50 mm in 54 cases, absent in one patient; septal leaflet downward displacement was 29.07 ± 12.34 mm in 134 cases, absent in 17 cases; and posterior leaflet downward displacement was 43.18 ± 19.16 mm in 115 cases, absent in 34 cases. Statistically, there was no significant difference between the results from 2D-ITEE and that of 2D-TTE. The consistency rates of 2D-ITEE with operation for septal and posterior leaflets were 93.2% and 96.1%, respectively, while the rate for anterior was only 40.1%, which was significantly different. Color Doppler flow image showed severe regurgitation in 150 cases and moderate in 14 cases. After surgical correction, moderate regurgitation of TV was found in 58 cases with 2D-ITEE, repair was performed again until the effect was satisfied. No complication occurred relating to the use of 2D-ITEE. CONCLUSIONS: 2D-ITEE could help diagnose anterior leaflet, evaluate the effect of TV repair, increase operational success rate, and reduce complication.

Persistent fifth aortic arch with interrupted aortic arch.

Persistent fifth aortic arch (PFAA) is one of the rarest congenital anomalies. We report a seven-month-old male with PFAA with upper arch interruption and lower arch coarctation diagnosed by echocardiogram and multidetector computed tomography.

Stripping voltammetric analysis of organophosphate pesticides using Ni/Al layered double hydroxides as solid-phase extraction.

A sensitive electrochemical stripping voltammetric biosensor is designed for organophosphate pesticides (OPs) based on solid-phase extraction (SPE) using Ni/Al layered double hydroxides (LDHs) modified glassy carbon electrode (labeled as Ni/Al-LDHs/GCE). The Ni/Al-LDHs as the host are highly efficient to capture OPs, which dramatically facilitates the enrichment of nitroaromatic OPs onto their surface and realizes the stripping voltammetric detection of OPs. The stripping voltammetric performances of methyl parathion (MP) intercalated into LDHs were evaluated by cyclic voltammetric and square-wave voltammetric (SWV) analysis. The combination of the host-guest supramolecular structure, SPE, and stripping voltammetry provides a fast, simple, and sensitive electrochemical method for detecting nitroaromatic OPs by using MP as a model. The stripping analysis is linear over the MP concentration ranges of 0.001-0.1 and 0.2-1.0 microg mL(-1) with a detection limit of 0.6 ng mL(-1) (S/N=3). The developed biosensor exhibits good reproducibility and acceptable stability. This study offers a new promising protocol for OPs analysis.

Ascending-to-descending aortic bypass via posterior pericardium for complex coarctation of aorta.

UNLABELLED: We introduce our surgical experience in treating recurrent aortic coarctation or coarctation associated with intracardiac abnormalities, which is difficult to manage. Four patients underwent the operation with hypothermic cardiopulmonary bypass. During the surgery, the posterior pericardium was opened and the thoracic aorta was dissected and sidebiting clamped, and an end-to-side anastomosis of the artificial graft to the descending aorta was performed. The graft was passed in between the inferior vena cava and the inferior right pulmonary vein and posterior to the pericardium. After that, the aorta was clamped and intracardiac repair was finished. Then the proximal artificial graft was anastomosed to the right side of the ascending aorta with heart beating. All patients recovered smoothly. There was no early or late death, without bleeding or other complications after operation. CONCLUSION: "Complex coarctation" can be treated with ascending-to-descending aortic bypass via posterior pericardium and satisfied result can be achieved.

Electrochemical biosensing of methyl parathion pesticide based on acetylcholinesterase immobilized onto Au-polypyrrole interlaced network-like nanocomposite.

We developed a simple strategy for designing a highly sensitive electrochemical biosensor for organophosphate pesticides (OPs) based on acetylcholinesterase (AChE) immobilized onto Au nanoparticles-polypyrrole nanowires composite film modifid glassy carbon electrode (labeled as AChE-Au-PPy/GCE). Where, the generated Au nanoparticles (AuNPs) were homogenously distributed onto the interlaced PPy nanowires (PPy NWs) matrix, constructing a three-dimensional porous network. This network-like nanocomposite not only provided a biocompatible microenvironment to keep the bioactivity of AChE, but also exhibited a strong synergetic effect on improving the sensing properties of OPs. The combination of AuNPs and PPyNWs greatly catalyzed the oxidation of the enzymatically generated thiocholine product, thus increasing the detection sensitivity. On the basis of the inhibition of OPs on the enzymatic activity of AChE, the conditions for OPs detection were optimized by using methyl parathion as a model OP compound. The inhibition of methyl parathion was proportional to its concentration ranging from 0.005 to 0.12 and 0.5 to 4.5 microgmL(-1). The detection limit was 2 ngmL(-1). The developed biosensor exhibited good reproducibility and acceptable stability. This study provides a new promise tool for analysis of organophosphate pesticides.

Early and midterm results in anatomic repair of Ebstein anomaly.

OBJECTIVE: We report the results of surgical treatment of Ebstein anomaly during a 10-year period, especially with an anatomic repair technique that restores to near normal anatomic and physiologic function of the tricuspid valve and the right ventricle. METHODS: Between December 1997 and December 2006, 83 consecutive patients aged 9 months to 52 years underwent operation for Ebstein anomaly. Among them, 78 underwent the anatomic repair technique (male 39). Tricuspid incompetence was moderate in 22 patients and severe in 56 patients. The main surgical technique includes excision of the atrialized right ventricle, detachment and repair of the leaflet, transposition of the leaflet, and anulus plication of the tricuspid valve. In some patients in whom the septal leaflet was severely hypoplastic or absent, a new leaflet was created with autologous pericardium. Biventricular repair was not performed in 5 patients with very severely hypoplastic tricuspid valves and poor right ventricular function. RESULTS: All patients survived and recovered uneventfully. For the 78 patients who underwent anatomic repair, postoperative echocardiography showed that tricuspid incompetence disappeared in 65 patients and was mild in 13 patients. Right ventricular function was good. Patients have been doing well during a mean follow-up of 46 months (2 months to 9 years). The latest follow-up echocardiograms showed that tricuspid incompetence was eliminated in 55 patients and was mild in 17, moderate in 3, and severe in 3. The 5 patients with a total cavopulmonary connection procedure and one-and-one-half-ventricle correction procedure are also doing well. CONCLUSIONS: Satisfactory early and midterm results can be achieved with the anatomic repair technique to correct Ebstein anomaly. Tricuspid valve replacement can be avoided in most patients.