Antioxidant and antibacterial hydrogel formed by protocatechualdehyde-ferric iron complex and aminopolysaccharide for infected wound healing.

To better treat bacteria-infected wounds and promote healing, new wound dressings must be developed. In this study, we obtained PA@Fe by chelating iron trivalent ions (Fe3+) with protocatechualdehyde (PA), which has a catechol structure. Subsequently, we reacted it with ethylene glycol chitosan (GC) via a Schiff base reaction and loaded vancomycin to obtain an antibacterial Gel@Van hydrogel with a photothermal response. The as-prepared Gel@Van hydrogel exhibited good injectability, self-healing, hemostasis, photothermal stability, biocompatibility, and antioxidant and antibacterial properties. Moreover, Gel@Van hydrogel achieved highly synergistic antibacterial efficacy through photothermal and antibiotic sterilization. In a mouse skin-damaged infection model, Gel@Van hydrogel had a strong ability to promote the healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, indicating the great potential application value of Gel@Van hydrogel in the field of treating and promoting the healing of infected wounds.

Turning Polysaccharides into Injectable and Rapid Self-Healing Antibacterial Hydrogels for Antibacterial Treatment and Bacterial-Infected Wound Healing.

Great efforts have been devoted to the development of novel and multifunctional wound dressing materials to meet the different needs of wound healing. Herein, we covalently grafted quaternary ammonium groups (QAGs) containing 12-carbon straight-chain alkanes to the dextran polymer skeleton. We then oxidized the resulting product into oxidized quaternized dextran (OQD). The obtained OQD polymer is rich in antibacterial QAGs and aldehyde groups. It can react with glycol chitosan (GC) via the Schiff-base reaction to form a multifunctional GC@OQD hydrogel with good self-healing behavior, hemostasis, injectability, inherent superior antibacterial activity, biocompatibility, and excellent promotion of healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The biosafe and nontoxic GC@OQD hydrogel with a three-dimensional porous network structure possesses an excellent swelling rate and water retention capacity. It can be used for hemostasis and treating irregular wounds. The designed GC@OQD hydrogel with inherent antibacterial activity possesses good antibacterial efficacy on both S. aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria), as well as MRSA bacteria, with antibacterial activity greater than 99%. It can be used for the treatment of wounds infected by MRSA and significantly promotes the healing of wounds. Thus, the multifunctional antibacterial GC@OQD hydrogel has the potential to be applied in clinical practice as a wound dressing.

Devastating the Supply Wagons: Multifaceted Liposomes Capable of Exhausting Tumor to Death via Triple Energy Depletion.

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H2O2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment.

Mitochondria-acting nanomicelles for destruction of cancer cells via excessive mitophagy/autophagy-driven lethal energy depletion and phototherapy.

Mitophagy is a specific self-protective autophagic process that degrades damaged or dysfunctional mitochondria, and is generally considered to reduce the effectiveness of mitochondria-targeted therapies. Here, we report an energy depletion-based anticancer strategy by selectively activating excessive mitophagy in cancer cells. We fabricate a type of mitochondria-targeting nanomicelles via the self-assembly of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and dc-IR825 (a near-infrared cyanine dye and a photothermal agent). The TPGS/dc-IR825 nanomicelles enable mitochondrial damage in cancer cells, which, for self-protection, activate two autophagic pathways, (1) mitophagy and (2) adenosine triphosphate (ATP) shortage-triggered autophagy. However, the excessive mitophagy/autophagy activities far surpass the degradative capacity of autolysosomes, leading to the formation of micrometer-sized vacuoles and degradation blockage. Immunofluorescence staining and Western blot analysis reveal that the nanomicelle-treated cancer cells are under severe ATP shortage, which eventually causes substantial cell death. Moreover, the nanomicelles intravenously injected into tumor-bearing mice show high tumor accumulation, long tumor retention, and inhibit the tumor growth by inducing excessive mitophagy/autophagy and energy depletion in tumor cells. Additional near-infrared laser irradiation treatment further enhances the in vitro and in vivo anticancer efficiencies of the nanomicelles, due to the excellent photothermal and photodynamic effects of dc-IR825. We believe that this work highlights the important role of mitophagy/autophagy in treating cancers.

Construction of Dually Responsive Nanotransformers with Nanosphere-Nanofiber-Nanosphere Transition for Overcoming the Size Paradox of Anticancer Nanodrugs.

Tumor microenvironment (TME)-responsive nanosystems represent a category of intelligent nanomaterials for precise anticancer drug delivery. Herein, we report a smart size-/morphology-switchable nanodrug that can respond to the acidic TME and near-infrared (NIR) laser irradiation for effective tumor ablation and tumor metastasis inhibition. The nanoagent is physically assembled by a cytolytic peptide, melittin (MEL), an NIR-absorbing molecule, cypate, and a tumor-targeting polymer, hyaluronic acid (HA). At pH 7.4, the as-formed MEL/Cypate@HA complexes are negatively charged nanospheres (∼50 nm), which are suitable for long-term systemic circulation. When these nanospheres actively target tumors, the weakly acidic TME triggers an in situ transformation of the nanospheres to net-like nanofibers. Compared with the nanospheres, the nanofibers not only exhibit an inhibitory effect on tumor cell mobility but also significantly prolong the retention time of MEL/Cypate@HA in tumor tissues for MEL-based chemotherapy. Moreover, the nanofibers can be photodegraded into small nanospheres (∼25 nm) by NIR laser irradiation during cypate-mediated photothermal therapy, which enables deep tumor penetration of the loaded MEL and thus achieves effective tumor eradication. This work provides a facile strategy for converting naturally occurring therapeutic peptides into a TME-responsive drug delivery system and may inspire the development of nanomaterials with changeable structures for therapeutic purposes.

Molecular Targeting-Mediated Mild-Temperature Photothermal Therapy with a Smart Albumin-Based Nanodrug.

Photothermal therapy (PTT) usually requires hyperthermia >50 °C for effective tumor ablation, which inevitably induces heating damage to the surrounding normal tissues/organs. Moreover, low tumor retention and high liver accumulation are the two main obstacles that significantly limit the efficacy and safety of many nanomedicines. To solve these problems, a smart albumin-based tumor microenvironment-responsive nanoagent is designed via the self-assembly of human serum albumin (HSA), dc-IR825 (a cyanine dye and a photothermal agent), and gambogic acid (GA, a heat shock protein 90 (HSP90) inhibitor and an anticancer agent) to realize molecular targeting-mediated mild-temperature PTT. The formed HSA/dc-IR825/GA nanoparticles (NPs) can escape from mitochondria to the cytosol through mitochondrial disruption under near-infrared (NIR) laser irradiation. Moreover, the GA molecules block the hyperthermia-induced overexpression of HSP90, achieving the reduced thermoresistance of tumor cells and effective PTT at a mild temperature (<45 °C). Furthermore, HSA/dc-IR825/GA NPs show pH-responsive charge reversal, effective tumor accumulation, and negligible liver deposition, ultimately facilitating synergistic mild-temperature PTT and chemotherapy. Taken together, the NIR-activated NPs allow the release of molecular drugs more precisely, ablate tumors more effectively, and inhibit cancer metastasis more persistently, which will advance the development of novel mild-temperature PTT-based combination strategies.

Efficient cell surface labelling of live zebrafish embryos: wash-free fluorescence imaging for cellular dynamics tracking and nanotoxicity evaluation.

Imaging the dynamics and behaviors of plasma membranes is at the leading edge of life science research. We report here the development of a universal red-fluorescent probe Chol-PEG-Cy5 for wash-free plasma membrane labelling both in vitro and in vivo. In aqueous solutions, the fluorescence of Chol-PEG-Cy5 is significantly quenched due to the intermolecular resonance energy transfer (RET) between neighbouring Cy5 moieties; however, upon membrane anchoring, the probes undergo lateral diffusion in lipid bilayers, resulting in weakened RET and turn-on fluorescence emission. We demonstrate that Chol-PEG-Cy5 enables rapid, stable and high-quality in vitro cell surface imaging in a variety of mammalian cells. Additionally, with the assistance of three-dimensional (3D) image reconstruction, we achieve for the first time the whole-mount in situ fluorescence imaging of the epidermal cell surfaces of live zebrafish embryos, which cannot be realized by conventional plasma membrane probes due to the presence of the surface-covering mucus barrier. This novel technique encourages us to track the cellular dynamics of the epidermis during embryonic development with 3D visualization. Moreover, we also develop a new method to evaluate the epidermal toxicity of nanomaterials (e.g., gold nanoparticles and graphene oxide nanosheets) toward zebrafish embryos using this fluorescent probe.

Development of a Light-Controlled Nanoplatform for Direct Nuclear Delivery of Molecular and Nanoscale Materials.

Research on nanomedicines has rapidly progressed in the past few years. However, due to the limited size of nuclear pores (9-12 nm), the nuclear membrane remains a difficult barrier to many nucleus-targeting agents. Here, we report the development of a general platform to effectively deliver chemical compounds such as drug molecules or nanomaterials into cell nuclei. This platform consists of a polyamine-containing polyhedral oligomeric silsesquioxane (POSS) unit, a hydrophilic polyethylene glycol (PEG) chain, and the photosensitizer rose bengal (RB), which can self-assemble into nanoparticles (denoted as PPR NPs). Confocal fluorescence imaging showed that PPR NPs mainly located in lysosomes after cellular internalization. After mild light irradiation, however, PPR NPs effectively disrupted lysosomal structures by singlet oxygen (1O2) oxidation and substantially accumulated on nuclear membranes, which enabled further disruption of the membrane integrity and promoted their final nuclear entry. Next, we selected two chemotherapeutic agents (10-hydroxycamptothecine and docetaxel) and a fluorescent dye (DiD) as payloads of PPR NPs and successfully demonstrated that this nanocarrier could efficiently deliver them into cell nuclei in a light-controlled manner. In addition to molecular compounds, we have also demonstrated that PPR NPs could facilitate the nuclear entry of nanomaterials, including Prussian blue NPs as well as gold nanorods. Compared to traditional strategies for nuclear delivery, this highly controllable nanoplatform avoids complicated modification of nucleus-targeting ligands and is generally applicable to both molecular compounds and nanomaterials.

Turning double hydrophilic into amphiphilic: IR825-conjugated polymeric nanomicelles for near-infrared fluorescence imaging-guided photothermal cancer therapy.

Developing biocompatible and photodegradable photothermal agents (PTAs) holds great promise for potential clinical applications in photothermal cancer therapy. Herein, a new PTA was innovatively constructed by conjugating the hydrophobic near-infrared (NIR) heptamethine cyanine molecule IR825-NH2 with a double hydrophilic block copolymer methoxypoly(ethylene glycol)5k-block-poly(l-aspartic acid sodium salt)10 (abbreviated as PEG-PLD) via amine-carboxyl reaction. The as-designed PEG-PLD(IR825) was amphiphilic and could self-assemble into polymeric nanomicelles in aqueous solutions. Benefiting from the chemical conjugation strategy, PEG-PLD(IR825) nanomicelles realized a considerably high drug loading rate (∼21.0%) and substantially avoided the premature release of IR825 during systemic circulation. Confocal imaging revealed that the nanomicelles mainly located at mitochondria and endoplasmic reticulum after cellular internalization. In vitro photothermal therapy demonstrated the excellent cancer killing efficiency of PEG-PLD(IR825) nanomicelles due to their high light-to-heat conversion efficiency upon NIR laser irradiation. In addition, PEG-PLD(IR825) nanomicelles showed polarity-sensitive fluorescence at ∼610 nm (under 552 nm excitation) and 830 nm (under 780 nm excitation), which was especially useful for both in vitro visible fluorescence imaging and in vivo near-infrared fluorescence imaging-guided photothermal therapy (PTT). At the in vivo level, PEG-PLD(IR825) nanomicelles exhibited an excellent tumor-homing ability and a long retention time in tumor tissues as evidenced by the in vivo fluorescence imaging results. The desirable properties of PEG-PLD(IR825) nanomicelles ensured their effective tumor ablation during PTT treatment. More importantly, the PEG-PLD(IR825) nanomicelles underwent degradation after laser irradiation, which ensured their post-treatment biosafety. Therefore, the nanomicelles are promising to serve as an efficient and safe PTA for imaging-guided photothermal cancer therapy.

Dual Channel Activatable Cyanine Dye for Mitochondrial Imaging and Mitochondria-Targeted Cancer Theranostics.

Because mitochondria are the key regulators for many cellular behaviors and are susceptible to hyperthermia and reactive oxygen species, mitochondria-specific reagents for simultaneous targeting, imaging, and treatment are highly desirable in cancer theranostics. Herein, we developed a mitochondria-targeted cyanine dye IR825-Cl, which possesses two separated excitation wavelength channels for both red fluorescence imaging and near-infrared (NIR) photothermal therapy (PTT). For imaging, IR825-Cl rapidly entered cells and selectively targeted mitochondria. Although IR825-Cl was completely quenched in water, interestingly, this dye had a turn-on response of red fluorescence (610 nm) in mitochondria under 552 nm excitation due to its polarity-responsive fluorescence emission. More interestingly, IR825-Cl realized the selective mitochondrial staining of cancer cells over normal cells and thus served as an ideal fluorescent probe for identifying cancer cells in normal tissues, which is extremely beneficial for cancer theranostics. For PTT, we demonstrated that under 808 nm NIR laser irradiation, this dye efficiently converted optical energy into heat, realizing mitochondria-targeted photothermal cancer therapy. Collectively, this molecule realized both high fluorescence emission (quantum yield > 43%) and effective light-to-heat conversion (17.4%), enabling its applications for wash-free fluorescence imaging for mitochondria and highly efficient fluorescence imaging-guided PTT.

[Left atrial and ventricular epicardial dual chamber pacing through a left lateral thoracotomy to treat pediatric complete atrioventricular block].

OBJECTIVE: To investigate the feasibility, advantages and efficacy of implantation of left atrial and ventricular epicardial dual chamber pacemaker to treat pediatric complete atrioventricular block. METHOD: Eleven children with median age 4.0 years (0.5-7.6 years) diagnosed as complete atrioventricular block resisting to drug therapy received implantations of left atrial and ventricular epicardial dual chamber pacemakers. Six were male and five female. Temporal or permanent right ventricular pacing was used for all of them before implantation of left atrial and ventricular epicardial dual chamber pacemakers. Three cases showed cardiac dysfunction. Left lateral thoracotomy was performed at 4th intercoastal space along anterior axillary line under general anesthesia, the pericardium was incised vertically anterior to the phrenic nerve, two pacing leads were individually located at left atrial appendage and left ventricular lateral wall. After all the parameters were detected to be satisfactory, a pouch was made at left abdomen under coastal margin. Dual chamber pacemaker was connected with pacing leads through subcutaneous tunnels. The sizes of heart chambers, cardiac functions, parameters of pacemaker, sensitivity, pacing status, PR interval and QRS interval were closely followed up post-operatively. RESULT: Implantations of pacemakers were successful for all of the patients with no complications associated with operations. Preoperative electrocardiograms showed QRS interval (180 ± 33)ms under right ventricular pacing, it decreased to (140 ± 24)ms after implantation of left atrial and ventricular epicardial dual chamber pacemaker, significantly lower than right ventricular pacing (t = 8.8, P < 0.05) . Atrioventricular (AV) interval was set at 90 ms, PR interval (124 ± 4)ms. Echocardiograms performed within 2-3 days after implantation of left atrial and ventricular epicardial dual chamber pacemakers showed that for the 3 cases who were previously under right atrial and right ventricular dual chamber pacing presenting cardiac dysfunction, their left ventricular diastolic diameter (LVDd) decreased from (46.3 ± 12.5) (32.0-55.0) ms to (44.7 ± 12.0) (31.0-53.0) mm and left ventricular ejection fraction (LVEF) increased from 30% ± 15% (18%-47%) to 44% ± 18% (33%-65%). During 2-14 months' follow up, LVEF increased progressively which became significantly higher than before (65% ± 8% vs. 30% ± 15%, t = 5.6, P < 0.05) . Cardiac chamber sizes and left ventricular systolic function for the other 8 patients maintain normal during follow up. Pacing status and sensitivity were satisfactory for all these patients during follow up. CONCLUSION: Implantation of left atrial and ventricular epicardial pacemaker might be considered for children diagnosed as complete atrioventricular block for whom endocardial pacemaker could not be implanted, due to its utmost protection for cardiac function with minimal injury and its ability to prevent or reverse pacemaker syndrome. Left atrial and left ventricular epicardium should be regarded as the first-choice and routine locations for epicardial pacing.

[Study on steroidal and triterpenoid constituents from Cissus pteroclada].

OBJECTIVE: To study the chemical constituents of ethnical drug Cissus pteroclada. METHODS: Silica gel column chromatography was employed to separate the constituents from EtOAc extraction of Cissus pteroclada and their structures were identified by physicochemical properties as well as spectrum analysis. RESULTS: Five steroidal compounds and 2 triterpenoid constituents were obtained. Their structures were identified as: stigmasterol (1), stigmasterol acetate (2), stigmasta-5, 22-dien-3-O-beta-D-glucopyranoside (3), beta-sitosterol (4), daucousterol (5), taraxerone (6), oleanolic acid (7). CONCLUSION: All the compounds are isolated from this plant for the first time except for compound 4 and 5. Compounds 1 - 3 are obtained from this genus for the first time.

[One-stage repair of congenital aortic arch disease with other cardiac defects by using autologous pulmonary artery tissue].

OBJECTIVE: To analyze the surgical strategy and result of one-stage repair for congenital aortic arch disease associated with other cardiac anomalies. METHODS: Between April 1993 and November 2009, 25 consecutive patients aged 26 d to 6.5 years underwent one-stage repair for congenital aortic arch disease with other cardiac anomalies. Among them, 6 patients had coarctation of aorta, 6 patients had interrupted aortic arch, and 13 cases had hypoplasia of aortic arch. The surgical techniques include excision of the anterior wall of pulmonary artery, resection of patent ductus arteriosus tissue, aortic arch reconstruction with autologous pulmonary artery wall, reconstruction of the pulmonary artery and repair of the associated defects. RESULTS: Twenty-four patients survived and recovered uneventfully. One patient died of pulmonary hypertension crisis in hospital. The reconstruction of the aorta and the correction of the intracardiac anomalies were proved by postoperative echocardiography and CT scan. There were no neurological or other complications. The follow-up showed that all patients developed normally and there were no restenosis of the aorta arch. CONCLUSIONS: With the benefits of growth potential and less tension, autologous pulmonary artery tissue is an optimal choice in aortic arch reconstruction. One-stage repair of congenital aortic arch disease associated with other cardiac anomalies can achieve good results.

[Staged total cavopulmonary connection for complex congenital heart diseases].

OBJECTIVE: To review the experience of staged total cavopulmonary connection (TCPC) in complex congenital heart diseases. METHODS: From June 1998 to March 2008, 22 patients underwent staged TCPC for complex congenital heart diseases. Among them, 9 were univentricular and pulmonary artery valve stenosis; 3 were univentricular and pulmonary artery atresia; 1 was transposition of great arteries, crisscross heart and pulmonary artery valve stenosis; 1 was complete atrioventricular canal defects, left ventricular hypoplasia, pulmonary artery atresia and atrioventricular valvular regurgitation; 1 was complete atrioventricular canal defects, left ventricular hypoplasia, pulmonary artery valve stenosis and atrioventricular valvular regurgitation after Glenn procedure; 1 was mirror image dextrocardia, single ventricle, pulmonary artery atresia, major aortopulmonary collateral arteries (MAPCAs) and right pulmonary arteriovenous fistula after Glenn procedure; 4 were tricuspid atresia and pulmonary artery valve stenosis; 1 was tricuspid atresia and pulmonary atresia; 1 was mirror image dextrocardia, double-outlet of right ventricle, left ventricular hypoplasia, pulmonary artery valve stenosis, tricuspid incompetence, and MAPCAs. Among them, 5 patients received systemic-to-pulmonary artery shunt, bidirectional Glenn procedure and TCPC. Seventeen patients received bidirectional Glenn procedure, the mean age was (5.9+/-4.4) years old. Pulmonary artery pressure pre-Glenn procedure was 17 to 20 mm Hg (1 mm Hg=0.133 kPa). Atrioventricular valve incompetence in 3 patients. Nakata index was less than 200 mm2/m2 in 4 patients before the first stage operation. The age of TCPC procedure was (9.6+/-4.9) years old, the interval time was (3.7+/-1.2) years. RESULTS: There was one in-hospital death, the mortality was 4.5%. The patient with univentricular and pulmonary atresia, received systemic-to-pulmonary artery shunt, bidirectional Glenn procedure and TCPC and died of pneumorrhagia. Other patients were recovered well, postoperative central venous pressure was 12 to 18 mm Hg, percutaneous oxygen saturation was 90% to 96%. The cardiac function were in NYHA class I to II. CONCLUSIONS: The staged TCPC was a good procedure in high-risk Fontan candidates. The results were satisfactory for those patients. This staged strategy may extend the operative indications for the Fontan procedure.

[Coronary artery bypass grafting in patients over 70 years old].

OBJECTIVE: To retrospectively analyze the experiences, indications, technique, and results of coronary artery bypass grafting (CABG) in patients over 70 years old. METHODS: Ninety-one patients received coronary artery bypass grafting from March 2004 to March 2008. Ages ranged from 70 to 83 years old, 22 patients over 75 years old. Conventional CABG (CCABG) in 72 patients, off-pump CABG (OPCAB) in 19 patients. Clinical data has no significant differences in two groups. The rate of using left internal mammary artery was 96.7%. The number of grafts in CCABG and OPCAB group were 2 to 5 (3.5 +/- 0.8) and 1 to 4 (2.9 +/- 0.7) respectively. RESULTS: In-hospital death in 2 cases, both were from chronic obstructive pulmonary disease and pulmonary infection. Cerebral infarction in 1 case and pulmonary infection in 2 cases in CCABG group, but no significant difference between two groups, and no difference in intubation, ICU stay, respiratory failure, renal function failure. But number of grafts in CCABG was significantly more than that in OPCAB (P < 0.01). Postoperative follow-up was 3 to 36 months, 1 case with recurrent angina in OPCAB. CONCLUSIONS: According to the characteristic of coronary artery disease in elderly, fully revascularization and improving myocardial blood supply, patients over 70 years old with CABG can obtain the same efficacy as younger patients. There were not significant difference between CCABG and OPCAB.

[Surgical treatment of complex congenital heart diseases with extracardiac conduit total cavopulmonary connection].

OBJECTIVE: To report the experience of extracardiac conduit total cavopulmonary connection (ECTCPC) in surgical treatment of complex congenital heart diseases. METHODS: From 1998 to 2006, 68 patients underwent ECTCPC for complex congenital heart diseases. Among them, 45 had functional univentricle with transposition of the great artery (TGA) and pulmonary artery valve stenosis, 19 had tricuspid atresia with hypoplasia of right ventricle, 4 had Ebstein's anomaly with hypoplasia of right ventricle. Six had left superior vena cava, 18 had received Bidirectional Glenn operation; Fifty-seven cases were performed under cardiopulmonary bypass with general anesthesia and hypothermia, 11 cases were performed without cardiopulmonary bypass. RESULTS: There were two death, the mortality was 2.9%. All patients were followed up from 1 to 8 years with no clinical symptoms and have been doing well. The arterial oxygen saturation was 90% - 96%, the cardiac function were in NYHA class I - II. CONCLUSION: The extra cardiac conduit TCPC is a simple procedure and superior to other type of Fontan procedure in most patients.