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Spirocycles play an important role in drug discovery and development. The direct, catalytic, and enantioselective synthesis of spirocycles from readily available starting materials and in an atom economic manner remains a highly sought-after task in organic synthesis. Herein, an enantioselective Pd-hydride-catalyzed cycloaddition method for the synthesis of spirocyclic compounds directly from two classes of commonly available starting materials, 1,3-enynes and cyclic carbon−hydrogen (C−H) bonds, is reported. The reactions employ a chiral Pd/WingPhos catalyst to both suppress the formation of bis-allenyl by-products and control the stereoselectivity. 1,3-Enynes are used as dielectrophilic four-carbon units in the cycloaddition reactions, which also enables an enyne substrate-directed enantioselectivity switch with good levels of stereocontrol. The present spirocycle synthesis tolerates a broad range of functional groups of 1,3-enyne substrates, including alcohols, esters, nitriles, halides, and olefins. A variety of diverse cyclic nucleophiles, including pharmaceutically important heterocycles and carbocycles, can be flexibly incorporated with spiro scaffolds., Spirocycles are traditionally difficult structures to synthesize due to the congested nature of the central atom. Here the authors show a method to synthesize quaternary carbon spirocycles in one step from 1,3-enynes and pyrazolidine-type heterocycles, both relatively unactivated structures, proceeding via palladium catalysis.

We demonstrate that α-aryl cyclic vinylogous esters are competent substrates in the direct intermolecular Pd-catalyzed asymmetric allylic alkylation, enabling a straightforward enantioselective synthesis of 6-allyl-6-aryl-3-ethoxycyclohex-2-en-1-ones, common motifs embedded in numerous structurally diverse natural products. As an initial demonstration of the utility of this protocol, the first catalytic enantioselective total synthesis of (+)-oxomaritidine and an improved five-step catalytic enantioselective synthesis of (-)-mesembrine have been completed divergently.

An unprecedented umpolung spirocyclopropanation reaction of p-quinone methides and α-keto carbonyls is described. Our umpolung strategy based on 1,6-conjugate addition and intramolecular nucleophilic substitution offers a new method for effective access to a series of highly functionalized spirocyclohexadienonyl cyclopropanes having two vicinal quaternary carbons in ≤98% yield and >20:1 dr. Significantly, cyclic and acyclic topological structures of α-keto carbonyls as 1,1-dipole one-carbon synthons have a distinct influence on the stereochemistry of products, showing a reversal of diastereoselectivity in this P(NMe2)3-mediated umpolung spirocyclopropanation.

A novel asymmetric catalytic (2+3) annulation of p-quinone methides with CN-substituted trimethylenemethane is described under palladium catalysis, providing an alternative approach for the enantio...

Chiral phosphoric acid-catalyzed biomimetic asymmetric [4 + 2] cycloaddition of ortho-alkenyl naphthols/phenols and ortho-quinone methides (o-QMs) has been demonstrated to afford various important 2,3,4-trisubstituted chromans in high yields with excellent enantio- and diastereoselectivities (up to 99% yield, 99% ee, >20:1 dr). Notably, this methodology not only enabled access to the trans-cis chiral trisubstituted chromans from 1-alkenyl 2-naphthols but also is compatible with 2-alkenyl 1-naphthols and phenols to deliver trans-trans chiral trisubstituted chromans.

A SPINOL-derived chiral phosphoric acid catalyzed asymmetric formal [2 + 3]-annulation of in situ generated alkynyl imines and 1,4-dithiane-2,5-diol has been developed to afford enantiopure α-alkynylated thiazolidones with up to 72% yield and 98.5 : 1.5 er. This tandem annulation involved a tandem S-addition of alkynyl imines/intramolecular acetalization, followed by PDC-mediated oxidation. The α-alkynylated thiazolidones could facilely afford the corresponding chiral α-alkynylated or α-alkenylated cyclic sulfoxides via further elaboration.

Direct enantioselective Michael-type Friedel–Crafts arylations and heteroarylations of s-cis 1-azadienes were achieved by applying chiral bifunctional tertiary amine-urea catalysts when using 2-naphthols as the nucleophiles, and phosphoric acid catalysts when using indoles as the nucleophiles. These two catalytic protocols efficiently enabled access to a diverse variety of important benzofuran-containing hetero-triarylmethanes in up to 98% yield and with 99.5 : 0.5 er.

A new tandem annulation of

Background: Early treatment of neonatal biliary atresia (BA) and other end-stage liver diseases can delay or prevent the necessity of liver transplantation (LT). The establishment of a standardized clinical pediatric liver transplantation (PLT) biobank is the prerequisite for scientific research, which helps to provide a qualified sample resource platform for research. Methods: Following standardized procedures to establish biobanks, the operational processes and quality control system were formulated. Liver tissue, blood, and stool samples undergoing LT were regularly collected, managed, and stored. Systematic management was conducted in collected specimens and corresponding clinical information. Results: Since implementation in August 2018, we have enrolled 49 unique subjects (0-18 years of age); the biobank contains nearly 3000 biospecimen aliquots. The most common LT diagnosis is BA (61.23%). Conclusion: The establishment of this biobank is a valuable resource that incorporates detailed clinical and biological information. It will help accelerate the pace of PLT discovery research. ClinicalTrials.gov ID: NCT04477967.

The strong binding ability of P-ylides with transition metals limits the utilization of stabilized P-ylide as nucleophiles in asymmetric organometallic catalysis. Herein we describe the first rhodium-catalyzed asymmetric ring-opening reaction of P-ylides utilizing oxabicyclic alkenes as the electrophilic partner. Various P-ylides including ester-, ketone- and amide-style P-ylides are all applicable. This asymmetric reaction occurs through the cleavage of two bridgehead C-O bonds and the formation of two C-C bonds, and oxabenzonorbornadienes are used as 1,4-biselectrophiles, thus providing access to benzonorcaradienes in good yields with high enantioselectivity and perfect diastereoselectivity. The present protocol also constitutes the first highly enantioselective direct catalytic asymmetric cyclopropanation of stabilized P-ylide nucleophiles.

The first Pd-catalyzed asymmetric allenylic [4+1] cycloaddition was successfully developed. Alternatively, tuning the Pd catalyst switched the reactivity toward an unprecedented [4+3] cycloaddition/cross-coupling. Ligands play a vital role in controlling the reaction pathway, allowing highly selective access to different products from identical substrates. Biological evaluation of the obtained compounds led to the discovery of new antitumor targets. A possible mechanism is proposed, suggesting two interesting catalytic cycles for the cycloaddition with palladium-butadienyls. This study also demonstrated the potential and utility of allenic esters as 1,4-biselectrophiles and C4 synthons for participating in cycloaddition reactions.

An unprecedented asymmetric catalytic (4 + 2) annulation reaction of aryl-substituted γ-methylidene-δ-valerolactones (GMDVs) with isatin-derived para-quinone methides (p-QMs) has been developed under the catalysis of palladium(0) and (S,S,S)-(-)-Xyl-SKP, offering a new approach for the diastereo- and enantioselective synthesis of chiral cyclohexadienone-fused cyclohexyl spirooxindoles. Significantly, three highly congested contiguous tetrasubstituted carbon atoms embedded in bispirocyclic skeleton, of which two are vicinal quaternary stereogenic centers, are forged in an effective and selective manner (up to 99% yield, up to 95% ee, >20/1 dr). The current reaction represents the first exploration of enantioselective catalytic (4 + 2) annulation forming the six-membered carbocycles in the chemistry of both GMDVs and p-QMs.

An unprecedented umpolung spirocyclopropanation reaction of

A novel asymmetric catalytic (2+3) annulation of

Chiral phosphoric acid-catalyzed biomimetic asymmetric [4 + 2] cycloaddition of

The development of enantiodivergent catalysis for the preparation of both enantiomers of a chiral compound is of importance in pharmaceutical and bioorganic chemistry. With the design of a class of reactive and stereoselective organocatalysts, acyclic chiral secondary amines, a method for achieving the enantiodivergence is developed simply by changing the secondary N-i-Bu- to N-Me-group within the catalyst architecture while maintaining the same absolute configuration of the catalysts, which modulates the catalyst conformation. This catalyst-controlled enantiodivergent method not only enables challenging asymmetric transformations to occur in an enantiodivergent manner but also features a high level of stereocontrol and broad scope that is demonstrated in eight different reactions (90 examples), all delivering both enantiomers of a range of structurally diverse products including hitherto less accessible, yet important, compounds in good yields with high stereoselectivities., Enantiodivergent methods, which to access both enantiomers of the same compound, are of importance in drug synthesis. Here, the authors show that by simply changing a NiBu- to a NMe-group in readily available amine organocatalysts, high stereocontrol and broad scope are achieved in eight asymmetric reactions.

N-Tosylhydrazones have had widespread application in organic synthesis for more than a half century. In most of cases, N-tosylhydrazones, as masked diazo compounds, have been generally used in a series of important carbon–carbon and carbon–heteroatom bond-forming reactions. This review provides an update on progress in diverse coupling reactions of N-tosylhydrazones since 2012. The examples selected are mainly categorized by metal-catalyzed and metal-free systems, wherein four main types of transformations including insertion, olefination, alkynylation, and cyclization are discussed for each system.1 Introduction2 Transition-Metal-Catalyzed Coupling Reactions3 Metal-Free Coupling Reactions4 Conclusion and Outlook

Catalytic asymmetric and divergent assembly of tricyclic and tetracyclic 3,3′-pyrrolidonyl spirooxindoles was developed, involving a one-pot chiral Bronsted base catalyzed asymmetric propargylation for the synthesis of oxindole 1,6-enynes and a subsequent switchable site-selective and highly diastereoselective electrophilic iodocyclization of 1,6-enynes. In addition, antitumor properties of the newly synthesized compounds were evaluated.

The first highly stereoselective intermolecular catalytic asymmetric dearomatization (CADA) of α-naphthols through C–C formation and the first asymmetric allylic dearomatization of naphthols by chiral organocatalysis have been achieved. These new and complete atom-economic reactions provide enantioriched α- and β-naphthalenones bearing an all-carbon quaternary center.

A novel strategy for the asymmetric construction of functionalized 4-aryl-3,4-dihydrocoumarins and 4-aryl-3,4-dihydroquinolin-2-ones via an intramolecular vinylogous Rauhut-Currier reaction of para-quinone methides (p-QMs) under the bifunctional catalysis of chiral amine-phosphine is described. This intramolecular mode for the catalytic enantioselective 1,6-conjugate addition of p-QMs has been explored for the first time, delivering two types of synthetically important heterocycles in high yields and enantioselectivites.

A novel Au-catalyzed [2 + 3] annulation reaction of enamides with propargyl esters has been developed, providing a new method for expeditious assembly of synthetically useful functionalized 1-azaspiro[4.4]nonane building blocks. Based on this key annulation, strategic installation of the pivotal azaspirocyclic core, followed by constructing the benzazepine unit via Witkop cyclization, led to the divergent total syntheses of cephalotaxine and cephalezomine H.

Lycopodium alkaloids with structural diversity and biological significance have been stimulating an increasing interest in the synthetic and medicinal communities, in which inspiration and exploration of their related biogenetic relationship generally constitute one of the major concerns. Driven by the plausible biogenetic entry to lycojaponicumin D as the first member of Lycopodium alkaloids having a structurally unusual C3-C13-linked scaffold, a new connection with lycodoline has been proposed and discovered on the basis of the design of an unprecedented bioinspired tandem fragmentation/Mannich reaction. Initiated by expeditious assembly of bridgehead heterofunctionalization in the [3.3.1] bicyclic system of lycodoline, a novel tandem palladium-mediated oxidative dehydrogenation/hetero-Michael reaction has been developed for the strain-driven formation of the C-heteroatom bond, leading to a new approach to conformationally rigid bridgehead heteroquaternary carbons. The present unified strategy provides a scenario for the divergent total syntheses of nine natural Lycopodium alkaloids and four unnatural C12 epimers, wherein (±)-lycojaponicumin D and six lycodoline-type alkaloids have been synthetically achieved for the first time.

A novel enantioselective [4 + 2] annulation of the allenoates having a unique positive ortho-effect with in situ generated ortho-quinone methides has been developed under the catalysis of Cinchona alkaloid. This chiral amine-catalyzed reaction provides an alternative route to asymmetric catalytic construction of synthetically interesting, highly functionalized chiral chromans in good to excellent enantioselectivities (up to 97% ee).

A novel base-mediated tandem spirocyclopropanation/rearrangement reaction of vinyl p-quinone methides (p-VQMs) with sulfonium salts is described. The unprecedented reactivity of p-VQMs was explored for the first time in the spiroannulation cascade, providing a stereoselective approach to the construction of synthetically interesting, densely functionalized spirocyclopentenyl p-dienones.

A novel strategy based on phase transfer catalysis for the diastereoselective and enantioselective direct assembly of unsymmetric β,β-diaryl-α-amino acid esters via 1,6-conjugate addition of para-quinone methides and glycine derivatives is described. This protocol also provides an alternative route to the synthetically interesting functionalized chiral tetrahydroisoquinoline and its analogues.

A novel DBU-mediated stereoselective spirocyclopropanation of para-quinone methides with sulfonium salts has been developed on the basis of the mode involving a 1,6-conjugate addition/intramolecular dearomatizing cyclization cascade. This reaction provides a mild and effective method for the assembly of synthetically and structurally interesting spirocyclopropanyl para-dienones. The feasibility for the enantioselective access to such functionalized para-dienones has also been explored by using the axially chiral sulfonium salt. Importantly, the regioselective ring openings of the related spirocyclopropanyl para-dienones have been achieved divergently.

The asymmetric catalytic 1,6-addition of p-QMs with racemic oxindoles under the bifunctional catalysis of C2-symmetric dimeric Cinchona-derived squaramide is described. This tertiary amine-squaramide catalyzed reaction provides a diastereoselective and enantioselective approach to the effective assembly of diverse diarylmethine-substituted oxindoles having vicinal tertiary and quaternary stereocenters.

A novel strategy based on phase transfer catalysis for the diastereoselective and enantioselective direct assembly of unsymmetric β,β-diaryl-α-amino acid esters via 1,6-conjugate addition of para-quinone methides and glycine derivatives is described. This protocol also provides an alternative route to the synthetically interesting functionalized chiral tetrahydroisoquinoline and its analogues.

The asymmetric catalytic 1,6-addition of p-QMs with racemic oxindoles under the bifunctional catalysis of C2-symmetric dimeric Cinchona-derived squaramide is described. This tertiary amine-squaramide catalyzed reaction provides a diastereoselective and enantioselective approach to the effective assembly of diverse diarylmethine-substituted oxindoles having vicinal tertiary and quaternary stereocenters.

A novel DBU-mediated stereoselective spirocyclopropanation of para-quinone methides with sulfonium salts has been developed on the basis of the mode involving a 1,6-conjugate addition/intramolecular dearomatizing cyclization cascade. This reaction provides a mild and effective method for the assembly of synthetically and structurally interesting spirocyclopropanyl para-dienones. The feasibility for the enantioselective access to such functionalized para-dienones has also been explored by using the axially chiral sulfonium salt. Importantly, the regioselective ring openings of the related spirocyclopropanyl para-dienones have been achieved divergently.

For the first time, cross-aldol reactions between acetaldehyde and activated acyclic ketones are achieved in the presence of chiral primary amine catalysts giving optically active tertiary alcohols with high enantioselectivities.

Highly enantioselective cross-aldol reactions between acetaldehyde and activated acyclic ketones are reported for the first time. Various acyclic ketones, such as saturated and unsaturated keto esters, reacted with acetaldehyde in the presence of a chiral primary amine and a Bronsted acid to afford optically enriched tertiary alcohols in good yields and with excellent enantioselectivities. Trifluoromethyl ketones were tolerable under the reaction conditions, thereby affording the trifluoromethyl carbinol in good-to-excellent yields and enantioselectivities. Structural modification of the chiral amines from the same chiral source switched the stereoselectivity of the products. The utility of aldol chemistry was demonstrated in the brief synthesis of functionally enriched δ-lactones. Theoretical calculations on the transition-state structure indicated that the protonated tertiary amine could effectively activate the carbonyl group of a keto ester to promote the addition process through hydrogen-bonding interaction and, simultaneously, provide an appropriate attacking pattern for the approach of the keto ester to the enamine, which is formed from acetaldehyde and the chiral catalyst, on a particular face, resulting in high enantioselectivity.

To our knowledge, elucidating the immune pathogenesis of disease, especially characteristic T-cell and natural killer (NK) cell expansions, has not been performed before now. We investigated the role of T lymphocytes and NK lymphocytes in the destruction of extrahepatic bile ducts of patients with biliary atresia.Lymphocytes from the liver and extrahepatic bile duct remnants of patients with biliary atresia were characterized by immunofluorescence staining, fluorescence-activated cell sorter analysis, and real-time reverse-transcriptase PCR. Cholangiocyte lysis assays were performed to confirm cytotoxicity of activated hepatic NK lymphocytes or CD8(+) cells.The inflammatory milieu from portal tracts and/or biliary remnants consisted of greater numbers of Kupffer cells, T lymphocytes, and NK lymphocytes in the patients with biliary atresia as compared with the cholestatic and noncholestatic controls. In patients with biliary atresia, expression of NK or CD8+ costimulatory molecules was upregulated as compared with controls. Hepatic NK lymphocytes or CD8(+) cells from patients with biliary atresia were demonstrated to be cytotoxic to the duct epithelium.Specific immune responses from NK and CD8(+) cells were involved in the injury to the duct epithelium and play a significant role in the phenotype of experimental biliary atresia.

To summarize experience of pediatric intensive care and explore the incidence of complications, the involved pathogens among liver recipients to determine the effective strategies for preventing complications.Between June 2006 and July 2009, 35 children under the age of 14 yr received 35 liver transplantations (LTs) performed at the center. A retrospective review of 22 infants weighing 8.8 kg or less underwent 23 transplants was conducted. Indication for transplantation was biliary atresia. Central venous pressure and arterial blood pressure were monitored continuously and fluid monitoring was performed every 2 hours in the first postoperative week. Blood loss, ascites, and intraoperative transudate loss were primarily replaced with 5% albumin and crystalloids to maintain a central venous pressure between 4 and 6 cm H(2)O. Oral food intake was allowed as soon as possible. To identify vascular or biliary complications, liver doppler ultrasound was performed intraoperatively immediately after reperfusion and after closure of the abdominal wall and postoperatively, twice daily during the first week after surgery. Immunosuppression was initially cyclosporine based, in combination with steroids. Cyclosporine was begun one day prior to transplantation at a dose of 10 mg/(kg·d) divided into two doses, except for cases with hepatic encephalopathy and severe infection. The subsequent doses were adjusted on the basis of recommended trough blood concentrations at different stages. Steroids were eventually discontinued at a time point exceeding 6 months after transplantation. The diagnosis of rejection was confirmed by histology on needle biopsy specimens. Acute graft rejection episodes were treated with a 3-day scheme of IV methylprednisolone 10 mg/(kg·d) followed by recycling doses during the following 3 days (7.5, 5 and 2.5 mg/(kg·d).The most common postoperative complications were infections (18 cases), gastrointestinal bleeding (3 cases), and vascular complications (4 cases). Rejection occurred in 25% of patients. There was one perioperative death from primary graft non-function. The most common isolated bacteria of the pathogen spectrum were Staphylococcus epidermidis. The median length of stay (LOS) in the PICU for 22 patients (23 transplants) was 10 days (range 5 - 21) and the mean length of stay in the hospital was (18.5 ± 116) days (range, 11 - 48 days). Mean requirement for artificial ventilation was 37.6 h. Mean use of dobutamine, prostaglandin E1 and dopamine was 3.3, 7.5 and 8.8 days, respectively. Preoperatively, 3 children had gastrointestinal bleeding, 18 had ascites, 2 had encephalopathy, 22 had jaundice, and 16 had coagulopathy. There were multiple early operative complications in these infants, including one graft with primary non-function (4.5%). Two patients (9.1%) returned for a total of three times for gastrointestinal bleeding or intra-abdominal hematoma. Three patients (13.6%) had early postoperative intestinal perforations related to adhesions or enterotomy, one was associated with a bowel obstruction. There were 26 episodes of bacterial or fungal infections in 18 (81.8%) patients in the early postoperative period, and infection was the direct/contributing cause of death in one infant. These infections included pneumonia, intra-abdominal abscess or sepsis. All of the bacterial and fungal infections were successfully treated with the appropriate antibacterial and antifungal agents, except for one patient who developed overwhelming sepsis after small bowel perforation. Four (18.2%) patients developed five episodes of acute allograft rejection during the first 15 days after LT. Three of the four patients who developed rejection were transplanted before 2007. All episodes of rejection were treated successfully with intravenous steroid pulse and optimization of cyclosporine levels or FK506 conversion. Of the 20 survivors beyond the perioperative period, two cases (10%) had hypertension requiring therapy.Liver transplantation in infants with biliary atresia appears technically demanding but acceptable. There should be essentially no age or size restriction for infants and transplantation can be performed with good outcome, although the frequency of complications is much higher than that seen in older children. The improvement in medical and nursing expertise in this group of very sick infants is based on judicious preoperative donor and recipient selection, meticulous surgical technique (vascular reconstruction and abdominal closure), immediate detection and prompt intervention of complications, and keen postoperative surveillance, which reflect a learning curve for both the technical aspects of liver transplantation and post-operative care of these very small patients in our institution. Liver transplantation for infants can be technically challenging.

To investigate the correlation between the graft volume calculated by 64-detector-row spiral computed tomography (CT) and the graft weight measured during the living donor liver transplantation (LDLT) operation, and try to get an equation to help determine the possible weight of graft before operation.23 donors with left lateral lobe LDLT were enrolled to undergo 64-detector-row spiral CT and the imaging data at the hepatic venous phase was used for whole and partial liver volumetric measurement on a dedicated image postprocessing workstation. The resected part of donor liver was weighed during the operation. Statistical analysis with SPSS15.0 was used to analyze the correlation between the estimated liver volume by CT and the actual graft weight.The graft volume calculated preoperatively by CT (293.35 ± 53.43 ml) was significantly larger than measured graft weight during the operation (252.82 ± 50.96 g) (P0.05). All corresponding pre- and intraoperative data correlated significantly (R = 0.885) (P0.001). Intraoperatively expected weight (W (intraop)) in grams and volume calculated preoperatively by CT (V (preop)) in milliliters can be calculated with the equation W (intraop) (g) = 0.844 × V (preop) (ml) + 5.271.Liver volume calculated by 64-detector-row spiral CT preoperatively can predict the actual graft weight, which is very useful in donor selection in LDLT.

Objective Activation of hedgehog (Hh) pathway has been implicated in the development of human malignancies. Hh as well as related downstream target genes has been extensively studied in many kinds of malignant tumours for clinical diagnostic or prognostic utilities. This study aimed at investigating whether Hh molecules provides a molecular marker of hepatoblastoma malignancy. Methods We obtained tissue sections from 32 patients with hepatoblastoma as well as cholestasis and normal control. Immunohistochemical analysis were performed to determine Hh signal components in human hepatoblastoma. The prognostic significance of single expression of Hh signal components were evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis for statistical analysis. Results Expression of Hh signal components showed an increase in hepatoblastoma compared with chole stasis and normal tissues. There was a positive correlation between Smo or Gli1 expression and tumor clinicopathological features, such as histological type, tumor grade, tumor size and clinical stage. Both Smo or Gli1 protein high expression was significantly associated with poor prognosis by univariate analyses and multivariate analyses. Conclusions Abnormal Hh signaling activation plays important roles in the malignant potential of hepatoblastoma. Gli1 expression is an independent prognostic marker.

To summarize our experience in adult-to-infant living donor liver transplantation (A-ILDLT) and to analyze the efficacy and complications of A-ILDLT.The clinical data, surgical strategies and complications of 28 adult donors and infantile recipients who underwent A-ILDLT from April 2006 to December 2009 were retrospectively analyzed. These 28 patients (14 boys and 14 girls) aged from 80 days to 11.5 months with body weights of 3.08 to 10.3 kg at the time of operation . They suffered from biliary atresia with decompensated cirrhosis. The living donors were 15 mothers, 9 fathers, 3 grandma and 1 elder brother with ABO compatible with the infantile recipients. 27 Donor organs were the left lateral lobe grafts (segment II, III) and 1 graft was segment II. All patients were followed up for 5 to 24 months.These grafts were orthotopically transplanted into the infantile recipients. The average length of stay was 9.3 days for the donor group without any complications. Postoperative immunosuppression included prednisone, Cyclosporin and mycophenolate mofetil (MMF). A total of 24 postoperative complications occurred in 20 recipients, including 5 vascular complications, 4 bleeding, 7 pneumonia, 2 bowel obstruction, 4 intestinal perforation and 3 rejection. Three recipients died of hepatic arterial thrombosis (HAT). The perioperative mortality rate of recipients was 10.7% (3/28) and the survival rate was 89.3% in peroperative period. One died of stricture of hepatic vein and 1 of accidental asphyxia during follow-up term. At present, 23 cases are still alive.A-ILDLT has become an effective method to infants with end-stage liver disease. The postoperative vascular complication is the predominant cause of death.

The cellular origin of myofibroblast in the liver fibrosis remains unclear. This study was designed to investigate whether biliary epithelial cells (BECs) undergoing epithelial–mesenchymal transition (EMT) might be found in patients with biliary atresia, thereby serving as a source of fibrotic myofibroblasts. Liver sections from patients with biliary atresia were evaluated to detect antigen for the BECs marker 4 and cytokeratin-7 (CK-7), proteins (fibroblast-specific protein 1, also known S100A4; the collagen chaperone heat shock protein 47, HSP47) characteristically expressed by cells undergoing EMT, as well as myofibroblasts marker a-smooth muscle actin (a-SMA). Normal bile ducts BECs could express CK-7 and low levels of a-SMA; they did not express S100A4 and HSP47. However, BECs from biliary atresia resulted in increased expression of a-SMA, S100A4, with concurrent transition to a fibroblast-like morphology and decreased expression of AK-7. Furthermore, BECs in biliary atresia were associated with significant bile ductular proliferation and coexpressed both epithelial and mesenchymal markers. From significant histologic evidence, the BECs forming small- and medium-sized bile ducts undergoing EMT may account for prominent bile ductular proliferation and directly contribute to fibrogenesis in BA.