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Background: The categorization of intrahepatic portal venous system (IHPS) patterns using wedged hepatic venous portography (WHVP) has proven to be an effective tool in the preoperative evaluation of Rex recessus and in identifying pediatric patients with extrahepatic portal vein obstruction (EHPVO) who are suitable for meso-Rex bypass (MRB). Despite this classification system being proposed a decade ago, its clinical application remains underutilized., Methods: A single-center retrospective study of 182 children with EHPVO was conducted between October 2014 and July 2023 when MRB was attempted. Data on demographics, etiology, imaging examinations, procedures, and follow-up were collected for 161 patients included. Two interventional radiologists used deVille's method to classify patients into types A to E based on WHVP imaging, with interobserver agreement analyzed. Associations between IHPS patterns and surgical outcomes following MRB were investigated., Results: Two radiologists had a high level of agreement on identifying IHPS patterns and suitable patients for MRB. Of the 161 cases, 130 were type A, 10 were type B, 5 were type C, 7 were type D, and 9 were type E. One hundred and forty-five patients with types A, B and C underwent successful MRB, showing feasibility for 90% of patients. Children categorized as types A and B experienced more significant benefits than type C, including intraoperatively decreased portal vein pressure, esophageal/gastric varices relief, decreased portal venous collaterals and a lower rate of bypass occlusion after one year. The surgical outcomes of patients with types A and B were not influenced by the diameter of the Rex recessus as suggested by WHVP., Conclusions: The majority of pediatric patients with EHPVO in mainland China have opportunities to receive successful MRB. There are potential differences in the etiology of Chinese and Western patients. The IHPS classification system aids in guiding preoperative surgical decisions and predicting hypotensive effects after MRB. Type C patients should be carefully chosen for MRB., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: The aim of our study was to analyze the medium-to long-term outcomes of Rex shunts in a large series of children with extrahepatic portal vein obstruction (EHPVO)., Methods: The clinical data of 105 children aged between 6 months and 16 years with EHPVO who underwent Rex shunt between October 2014 and June 2021 at our center were retrospectively reviewed after more than 2 years of follow-up., Results: The overall patency rate of the Rex shunt was 91.43% (96/105) during a median follow-up of 41 months (range, 24-98 months). Eighty-seven (82.86%) of the 105 patients underwent classical Rex shunt with internal jugular vein (IJV) bypass, and the remaining 18 patients (17.14%) underwent modified Rex shunt with intra-abdominal vein bypass. Patients with a patent shunt experienced portal hypertension resolution, which was characterized by a reduction in portal pressure, disappearance of variceal bleeding, relief of gastroesophageal varices, and relief of splenomegaly or hypersplenism. The rate of Rex shunt thrombosis in our center was 8.57% (9/105), and a repeat Rex shunt was effective for the treatment of graft thrombosis. Anastomotic stenosis occurred in 14.26% (15/105) of the children, 38.46% (5/13) of whom received successful endovascular intervention therapy and experienced remission of portal hypertension symptoms. The patency rate of the classical Rex shunt was higher than that of the modified Rex shunt (97.70% vs. 61.11%), whereas the rate of vascular complications, including anastomotic stenosis and graft thrombosis, of the classical Rex shunt was lower than that of the modified Rex shunt (11.49% vs. 77.78%). Further comparison revealed that the risk of vascular complications was substantially greater in the modified Rex shunt group than in the classical Rex shunt group in the nonadjusted model, minimally adjusted model, and fully adjusted model (RR ranged from 6.77 to 7.07, all p < 0.001)., Conclusions: The Rex shunt provides medium-to long-term benefits for children with EHPVO. The classical Rex shunt with IJV bypass provides the best patency rate and the fewest vascular complications., Levels of Evidence: Ⅲ TYPE OF STUDY: Retrospective comparative study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Total cyst excision and Roux-en-Y hepaticojejunostomy is the standard procedure for treating congenital choledochal cysts, which requires high surgical skills. Our aim is to introduce the experience with the SHURUI single-port robotic system in pediatric surgery., Presentation of Case: In this study, we present a case demonstrating the application of the SHURUI single-port robotic system in performing choledochal cyst excision and Roux-en-Y hepaticojejunostomy in a pediatric patients. Roux-en-Y anastomosis was constructed extracorporeally, then choledochal cyst excision and hepaticojejunostomy was performed intracorporally using the SHURUI Surgical System. Surgical complications and the wound outcomes were assessed. The total duration of the operation was 292 min, comprising an extracorporeal time of 45 min, docking time of 19 min, and intracorporal time of 183 min. The estimated blood loss was minimal at only 2 mL. The patient was discharged 6 days post-operation, and exhibited satisfactory recovery at the one-month follow-up., Discussion: This case represents an initial experience with the SHURUI Surgical System in managing a pediatric choledochal cyst. The results indicate that the system is feasible and safe for this procedure, and may have some advantages over laparoscopic and open approaches., Conclusion: The SHURUI Surgical System is both feasible and safe in pediatric surgery, and it may offer certain advantages over laparoscopic and open approaches., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Necroptosis is a kind of programmed cell death that causes the release of damage-associated molecular patterns and inflammatory disease including skin inflammation. Activation of receptor-interacting serine/threonine kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) is the hallmark of tumour necrosis factor α (TNF)-induced necroptosis. Here, we screened a small-molecule compound library and found that saracatinib inhibited TNF-induced necroptosis. By targeting MLKL, Saracatinib interfered with the phosphorylation, translocation, and oligomerization of MLKL induced by TNF. Consistently, mutation of the saracatinib-binding site of MLKL reduced the inhibitory effect of saracatinib on TNF-induced necroptosis. In an imiquimod (IMQ)-induced psoriasis mouse model, saracatinib effectively blocked MLKL phosphorylation and inflammatory responses in vivo. Taken together, these findings indicate that saracatinib inhibits necroptosis by targeting MLKL, providing a potential therapeutic approach for skin inflammation-related diseases such as psoriasis., (© 2024. The Author(s).)

Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis. According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups. We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1. Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases., (© 2023. Springer Nature Limited.)

Background & Aims: Our previous study indicated that CD177 + neutrophil activation has a vital role in the pathogenesis of biliary atresia (BA), which is partially ameliorated by N -acetylcysteine (NAC) treatment. Here, we evaluated the clinical efficacy of NAC treatment and profiled liver-resident immune cells via single cell RNA-sequencing (scRNA-seq) analysis to provide a comprehensive immune landscape of NAC-derived immune regulation., Methods: A pilot clinical study was conducted to evaluate the potential effects of intravenous NAC treatment on infants with BA, and a 3-month follow-up was carried out to assess treatment efficacy. scRNA-seq analysis of liver CD45 + immune cells in the control (n = 4), BA (n = 6), and BA + NAC (n = 6) groups was performed and the effects on innate cells, including neutrophil and monocyte-macrophage subsets, and lymphoid cells were evaluated., Results: Intravenous NAC treatment demonstrated beneficial efficacy for infants with BA by improving bilirubin metabolism and bile acid flow. Two hepatic neutrophil subsets of innate cells were identified by scRNA-seq analysis. NAC treatment suppressed oxidative phosphorylation and reactive oxygen species production in immature neutrophils, which were transcriptionally and functionally similar to CD177 + neutrophils. We also observed the suppression of hepatic monocyte-mediated inflammation, decreased levels of oxidative phosphorylation, and M1 polarisation in Kupffer-like macrophages by NAC. In lymphoid cells, enhancement of humoral immune responses and attenuation of cellular immune responses were observed after NAC treatment. Moreover, cell-cell interaction analysis showed that innate/adaptive proinflammatory responses were downregulated by NAC., Conclusions: Our clinical and scRNA-seq data demonstrated that intravenous NAC treatment partially reversed liver immune dysfunction, alleviated the proinflammatory responses in BA by targeting innate cells, and exhibited beneficial clinical efficacy., Impact and Implications: BA is a serious liver disease that affects newborns and has no effective drug treatment. In this study, scRNA-seq showed that NAC treatment can partially reverse the immune dysfunction of neutrophil extracellular trap-releasing CD177+ neutrophils and Kupffer cells, and lower the inflammatory responses of other innate immune cells in BA. In consequence, intravenous NAC treatment improved the clinical outcomes of patients with BA in term of bilirubin metabolism., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

Purpose: To review our single-center surgical outcomes of redo operations after failed Rex shunt procedures., Methods: From September 2017 to October 2021, a total of 20 patients (11 males, 9 females; median age: 8.6 years) with Rex shunt occlusions were admitted to our hospital. Two of these patients were previously operated on in our hospital, and the remaining 18 were from other centers. All patients underwent repeat operations after detailed preoperative evaluations., Results: Preoperative wedged hepatic vein portography (WHVP) was conducted for 18 patients. Thirteen patients exhibited well-developed Rex recessus and intrahepatic portal vein during WHPV examination, consistent with the intraoperative exploration results. Fifteen patients (75%, 15/20) underwent redo-Rex shunt, four underwent Warren shunt and one underwent devascularization surgery. During the redo-Rex shunt operations, the left internal jugular veins (IJV) were used as bypass grafts in 11 patients; the intra-abdominal veins were used in 4 patients. The patients were followed up for 12-59 months (mean, 24.8 months). After redo Rex shunts, the grafts were patent in 14 patients (93.3%, 14/15), but 1 graft had thrombosis (6.7%, 1/15). Three patients suffered from postoperative anastomotic stenosis, and all of the stenosis was relieved with balloon dilatations. After re-Rex shunts, esophageal varices and spleen size were substantially reduced, and the platelet count significantly increased. Postoperative graft thrombosis was found in 1 patient after Warren shunt (1/4, 25%), and there was no graft stenosis. Compared with Warren surgery, patients who underwent re-Rex shunt had a significantly higher rate of platelet increase., Conclusions: Redo-rex shunts can be finished in most patients with failed Rex shunts. Re-Rex shunt is a preferred surgical choice after a failed Rex shunt when a good bypass graft is available, and the surgical success rate can reach more than 90%. A suitable bypass graft is essential for a successful redo Rex shunt. Preoperative WHVP is recommended for the design of a redo surgical plan preoperatively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wen, Wang, Yang, Liu, Liang, Liang, Ning, You, Bai and Hong.)

Background: Biliary atresia (BA) is a type of severe cholestatic childhood disease that may have a genetic component. miR-100 plays a key role in regulating cell apoptosis, proliferation, and inflammatory reactions. A single-nucleotide polymorphism in miR-100 has been proven to modulate susceptibility to various diseases., Methods: We conducted a case-control retrospective study to explore the correlation between miR-100 gene polymorphism (rs1834306 A>G) and biliary atresia susceptibility in 484 Chinese patients and 1445 matched control subjects., Results: Our results showed that rs1834306 A>G was correlated with a significantly increased risk for BA (GG vs. AA: adjusted odds ratio (OR) = 1.44, 95%confidence interval (CI) = 1.02-2.03, p = 0.041; and GG vs. AA/AG: adjusted OR = 1.39, 95%CI = 1.02-1.89, p = 0.036)., Conclusions: Our results showed that the rs1834306 A>G polymorphism is associated with an increased risk for BA and contributes to BA susceptibility., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiaming Chang et al.)

Fully bio-based adhesives are beneficial to reduce the dependence of the wood adhesive industry on synthetic resins based on petrochemical resources and enhance the market competitiveness of adhesives. A fully bio-based wood adhesive composed of tannin and sucrose was developed and successfully used in the preparation of plywood. Effects of the preparation technology on the bonding strength and water resistance of plywood were investigated, and the properties of the adhesive were analyzed by Fourier transform infrared spectroscopy (FT-IR), thermogravimetry (TG) and X-ray diffraction (XRD) in this study. The results showed that: (1) Compared with other biomass adhesives, tannin-sucrose adhesive had the characteristics of high-solid content and low viscosity, which had the potential to prepare particleboard and fiberboard. (2) A proper mass ratio of tannin to sucrose was key to obtaining a tannin-sucrose adhesive with better properties. (3) The optimum preparation process of tannin-sucrose adhesive for plywood was as follows: hot-pressing temperature of 210 °C, hot-pressing time of 1.2 min/mm, m(tannin):m(sucrose) of 60:40 and adhesive loading of 160 g/m 2 . Under these conditions, the water-resistant bonding strength of the plywood was 0.89 MPa, which met the strength requirements of the Type II standard of plywood in GB/T 17657-2013. (4) The hot-pressing temperature played a decisive role in the tannin-sucrose adhesive, and the good performance of the plywood was maintained when the temperature was 210 °C or above. Thus, the prepared tannin-sucrose adhesive had high-bonding strength, good water resistance and thermal stability.

Background & Aims: We have previously reported on the potential pathogenic role of neutrophils in biliary atresia (BA). Herein, we aimed to delineate the role of CD177+ neutrophils in the pathogenesis of BA., Methods: Immune cells from the livers of mice with rhesus rotavirus-induced BA were analysed. Single-cell RNA-sequencing was performed to specifically analyse Gr-1 + (Ly6C/Ly6G + ) cells in the liver. Gene expression profiles of CD177 + cells were analysed using the Smart-Seq RNA-sequencing method, and the pathogenesis of BA was examined in Cd177 -/- mice. Neutrophil extracellular trap (NET) inhibitors were used to determine the role of CD177 + cell-derived NETs in BA-associated bile duct damage, and a pilot clinical study evaluated the potential effects of N-acetylcysteine on NET release in BA., Results: Increased levels of Gr-1 + cells were observed in the livers of mice with rhesus rotavirus-induced BA. RNA-sequencing analysis revealed that CD177 + cells were the main population of Gr-1 + cells and expressed elevated levels of both interferon-stimulated and neutrophil degranulation genes. Cd177 -/- BALB/c mice exhibited delayed disease onset and reduced morbidity and mortality. High numbers of mitochondria were detected in CD177 + cells derived from mice with BA; these cells were associated with increased levels of reactive oxygen species and increased NET formation, which induced the apoptosis of biliary epithelial cells in cocultures. In a pilot clinical study, the administration of N-acetylcysteine to patients with BA reduced CD177 + cell numbers and reactive oxygen species levels, indicating a potential beneficial effect., Conclusions: Our data indicate that CD177 + cells play an important role in the initiation of BA pathogenesis via NET formation., Clinical Trial Registration: The pilot study of N-acetylcysteine treatment in patients with BA was registered on the Chinese Clinical Trial Registry (ChiCTR2000040505)., Lay Summary: Neutrophils (a type of innate immune cell, i.e. an immune cell that doesn't target a specific antigen) are thought to play a role in the development of biliary atresia (a rare but potentially lethal condition of the bile ducts that occurs in infants). Herein, we found that neutrophils expressing a particular protein (CD177) played an important role in bile duct damage by releasing a special structure (NET) that can trap and kill pathogens but that can also cause severe tissue damage. A pilot study in patients with biliary atresia showed that inhibiting NETs could have a beneficial effect., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

In order to improve the initial viscosity and stability of Camellia oleifera cake-protein adhesive, Camellia oleifera cake-protein was blended with defatted soybean protein (DSP), soybean protein isolate (SPI), and casein, followed by adhesive preparation through degradation and crosslinking methods. The performance of Camellia oleifera cake-protein adhesive was investigated by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopic (SEM), and thermogravimetric (TG) and X-ray diffraction (XRD). The results showed that DSP, SPI, and casein likely promoted the effective degradation of Camellia oleifera cake-protein, and, thus, more active groups were formed in the system, accompanied by more reactivity sites. The prepared adhesive had a lower curing temperature, and higher initial viscosity and stability, but the storage time was shortened. Moreover, DSP, SPI, and casein, themselves, were degraded into peptide chains with lower molecular weights; thus, improving the overall flexibility of the adhesive, facilitating a better elastic contact and regular array between crosslinking products, and further strengthening the crosslinked structure and density of the products. After curing, a compact and coherent reticular structure was formed in the adhesive layer, with both bonding strength and water resistance being significantly improved. According to the results obtained, the next step will be to study the DSP-modified Camellia oleifera cake-protein adhesive in depth.

Introduction: Correctly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants., Patients and Methods: The data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups., Results: A total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3 + T cells, CD3 + CD4 + T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA., Conclusions: Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1 + effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology., Competing Interests: Declaration of Interests The authors declare an application of patents describing diagnosis and treatment of BA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: COVID-19 has become one of the most serious global epidemics in the 21st Century. This study aims to explore the distribution of research capabilities of countries, institutions, and researchers, and the hotspots and frontiers of coronavirus research in the past two decades. In it, references for funding support of urgent projects and international cooperation among research institutions are provided., Method: the Web of Science core collection database was used to retrieve the documents related to coronavirus published from 2003 to 2020. Citespace.5.6.R2, VOSviewer1.6.12, and Excel 2016 were used for bibliometric analysis., Results: 11,036 documents were retrieved, of which China and the United States have contributed the most coronavirus studies, Hong Kong University being the top contributor. Regarding journals, the Journal of Virology has contributed the most, while in terms of researchers, Yuen Kwok Yung has made the most contributions. The proportion of documents published by international cooperation has been rising for decades. Vaccines for SARS-CoV-2 are under development, and clinical trials of several drugs are ongoing., Conclusions: international cooperation is an important way to accelerate research progress and achieve success. Developing corresponding vaccines and drugs are the current hotspots and research directions., Competing Interests: The authors declare no conflict of interest.

Introduction and objectives: This study assessed the diagnostic protocol and the outcomes of laparoscopic aberrant hepatic duct (AHD) reconstruction in choledochal cyst (CC) surgery. Methods: From January 2010 to January 2018, 275 laparoscopic CC excisions were conducted in our hospital. Seven patients of CC with associated AHD were recorded. AHDs that drained into the cystic duct were anastomosed to the Roux-en-Y loop. Clinical data of these 7 patients were retrospectively analyzed. Results: AHD is classified into four types according to the literature. The type where AHD drains into the cystic duct is the most commonly encountered one. The incidence of this type was 2.5% (7/275) in our series. Preoperative examination included magnetic resonance cholangiopancreatography (MRCP) (5 patients) and computed tomography (CT) scan (2 patients). Suspected AHD was diagnosed preoperatively in 4 out of the 5 patients who underwent MRCP. For the 2 patients who underwent CT scan only, AHD was not detected preoperatively. AHD was verified intraoperatively for all the 4 patients who had suspected diagnosis. Among them, AHD was well preserved in 3 patients, but damaged at exploration in the remaining 1. For the remaining 3 patients without preoperative AHD diagnosis, bile leakage was detected intraoperatively. Ductoplasty of the AHD with common hepatic duct was performed in 3 patients, and AHD was incorporated into the Roux-en-Y jejunal loop separately in 4 patients. Laparoscopic surgical procedures were completed in 6 of the 7 patients in this study, while 1 patient was converted into an open procedure. Postoperative recovery was uneventful in all patients. The duration of follow-up ranged from 6 months to 4 years (median 2 years) with no complication encountered. Conclusions: Routine preoperative MRCP examination of CC is recommended to detect variations of biliary tree. The laparoscopic approach is a feasible option in the experienced hands.

To find the effects of cross-linker phenol-formaldehyde (PF) resin on the performance of soy-based adhesives, the reaction between model compounds hydroxymethyl phenol (HPF) and glutamic acid were studied in this paper. HPF prepared in laboratory conditions showed higher content of hydroxymethyl groups than normal PF resin, which was proved by the results of Electrospray Ionization Mass Spectrometry (ESI-MS) and 13 C Nuclear Magnetic Resonance ( 13 C-NMR). The results of ESI-MS, Fourier transform infrared spectroscopy (FT-IR), and 13 C-NMR based on resultant products obtained from model compounds showed better water resistance of the soy protein-based adhesive modified by PF-based resin, which indicated the reaction between PF resin and soy protein. However, it seemed that the soy-based adhesive cross-linked by HPF with the maximum content of hydroxymethyl groups did not show the best water resistance.

Biliary atresia (BA) has complex genetic etiology, characterized by different levels of hepatic fibrosis after the Kasai procedure and immune responses to the bile duct. As an activator of the two most important inflammatory cells in Biliary atresia (T cells and NK cells), IL-18 is significantly increased in BA patients. This study aims to investigate the association of Interleukin 18(IL-18) with the susceptibility to BA. We examined the association of three polymorphisms (rs549908, rs187238 and rs1946518 in IL-18) and BA susceptibility in a Southern Chinese population composed of 506 cases and 1473 controls. SNP rs187238 and rs1946518 were identified as associated with BA. Interestingly, we also observed that the intragenic synergistic epistasis between SNPs rs187238 and rs1946518 boosting the risk to BA by logistic regression and Multifactor dimensionality reduction (MDR) analysis. This study provides for the first time a direct evidence to support IL-18 as a susceptibility gene for the disease in southern Chinese children., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Gonorrhea, an important sexually transmitted disease, is becoming a growing public health problem around the globe. Vaccination is considered the best long-term approach for control of infection. In this study, we designed a novel Neisseria gonorrhoeae (N. gonorrhoeae) DNA vaccine delivered by bacterial ghosts and characterized its immune responses in vitro and in vivo. Our results demonstrate that bacterial ghosts greatly promoted BMDCs maturation and activation. Bacterial ghosts loaded with N. gonorrhoeae DNA vaccine were efficiently taken up by mouse macrophage RAW264.7 cells. Furthermore, oral immunization with the ghost vaccine candidate elicited greater CD4 + and CD8 + T cell responses and induced higher IgG responses than N. gonorrhoeae DNA vaccine alone. In addition, mice immunized with the vaccine candidate responded with a significant rise in bactericidal antibody titer. These results suggest that bacterial ghosts may function as a vaccine adjuvant by promoting BMDCs maturation, which in turn enhances the immune responses to the vaccine antigens. This study also highlights the potential of using bacterial ghosts as antigen delivery system in the development of an efficacious gonorrhea vaccine., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To guide the preparation of protein-based adhesive, especially the soy-based adhesive, the reaction between a simple dipeptide N -(2)-l-alanyl-l-glutamine (AG), being used as a model compound of protein, and its cross-linker furfuryl alcohol were studied in this paper. The products that were prepared with furfuryl alcohol and AG under different pHs were analyzed by ESI-MS, 13 C NMR, and FT-IR. It was found that the medium environment had great effects on the competition of the co-condensation reaction between furfuryl alcohol and AG and self-condensation reaction of furfuryl alcohol molecules in the mixing system with furfuryl alcohol and AG. Under alkaline conditions, both co- and self-condensation were not obviously detected. Only when the value of pH was higher than 11, were a few co-condensation reaction products gotten. The reaction occurred mainly between furfuryl alcohol and the primary amido groups of AG. Under acid conditions, both co- and self-condensation were observed. The more acid the preparation conditions were, the easier to be observed the self-condensation of furfuryl alcohol molecules would be than the co-condensation between furfuryl alcohol and AG. When the value of pH was higher than 5, both co- and self-condensation were not outstanding. In this study, under pH 3, the co- and self-condensation found equilibrium. There was a great possibility for the primary amido and aliphatic amino groups of AG molecules to react with furfuryl alcohol molecules. No reaction was detected between the secondary amido groups of AG and furfuryl alcohol., Competing Interests: The authors declare no conflict of interest.

The base-catalyzed resorcinol-formaldehyde condensation reactions were theoretically investigated in this study by employing a quantum chemistry method. The condensation reaction includes two steps: (1) formation of the quinonemethide (QM) intermediate from hydroxymethylresorcinol; (2) Michael addition between the quinonemethide and resorcinol anion. The first step is the rate-determining step. Two mechanisms, unimolecular elimination of the conjugate base (E1cb) and water-aided elimination (WAE), were identified for the formation of QM. The hydroxymethylresorcinol anion produces neutral QM while the dianion produces a quinonemethide anion (QMA). The calculated potential energy barriers suggested that the QMA formation is much more favorable. Although resorcinol-formaldehyde and phenol-formaldehyde condensations share a common mechanism, the former would be faster if the QMA participates in condensations. The potential energy barriers for formation of 2-QM, 4-QM, 6-QM, 2-QMA, and 4-QMA were calculated. The results show that the formations of 6-QM and 4-QMA have relatively lower energy barriers. This rationalized previous experimental observations that the 2,4-(2,6-) and 6,6'-(4,4'-) methylene linkages were dominant, whereas the 2,2'-linkage was almost absent. The resorcinol-phenol-formaldehyde co-condensations were also calculated. The cold-setting characteristic of phenol-resorcinol-formaldehyde co-condensed resin can be attributed to participation of resorcinol quinonemethides in condensations., Competing Interests: The authors declare no conflict of interest.

Base-catalyzed urea⁻formaldehyde condensation reactions were investigated by using a quantum chemistry method. It was found that monomethylolurea or N , N '-dimethylolurea can produce the methyleneurea intermediate (⁻HN⁻CO⁻N=CH₂) with the catalysis of base. The E1cb (unimolecular elimination of conjugate base) mechanism was identified for the formation of such an intermediate. The potential energy barrier was theoretically predicted to be 59.6 kJ/mol for the E1cb step, which is about half of that of previously proposed S N 2 (bimolecular nucleophilic substitution) mechanism. In the subsequentcondensation reactions, Michael addition reactions that lead to different condensed structures can occur between the methyleneurea intermediate and the anions produced from methylolureas under alkaline conditions. Based on the theoretical calculations on the kinetics and thermodynamics of the selected reactions, the competitive formations of methylene linkages, ether linkages and uron were discussed in combination with our previous experimental observations., Competing Interests: The authors declare no conflict of interest.

The purpose of this article is to report the status of the efficacy of and long-term adherence to the Bowel Management Program (BMP) for fecal incontinence (FI) postoperation in China.Children over 3 years of age with FI postoperation referred to our medical center were included in the study. Evaluations were performed before and 2 years after their clinic visit. The cost of bowel care, improvement in incontinence, health-related quality of life, and family functioning with the BMP were analyzed.A total of 48 children with FI were included in our study, of whom 38 were boys. The median treatment fee was 660.1 dollars. The complications included abdominal pain (4 patients, 8%), occasional vomiting (2 patients, 4%), and hypoglycemia (1 patient, 2%). The incontinence status and health-related quality of life improved significantly after the BMP. Despite the good outcome of the BMP, half of the patients discontinued the program.The BMP is an effective approach to manage FI and improve the patients' quality of life. Poor long-term adherence is currently the main challenge affecting the BMP application in China.

1,3-dimethylurea (DMU) was used to mimic urea and to model melamine-urea-formaldehyde (MUF) co-condensation reactions. The products of 1,3-dimethylurea-formaldehyde (DMUF), melamine-formaldehyde (MF), and melamine-1,3-dimethylurea-formaldehyde (MDMUF) reactions under alkaline and weak acidic conditions were compared by performing quantitative carbon-13 nuclear magnetic resonance ( 13 C-NMR) analysis. The effect of pH on the co-condensation reactions was clarified. With the presence of the methyl groups in DMU, the appearance or absence of the featured signal at 54⁻55 ppm can be used to identify the co-condensed methylene linkage ⁻N(⁻CH₃) ⁻CH₂⁻NH⁻. Under alkaline condition, MDMUF reactions produced primarily MF polymers and the featured signal at 54⁻55 ppm was absent. Even though the co-condensations concurrently occurred, undistinguishable and very minor condensed structures with ether linkage were formed. Differently, under weak acidic condition, the relative content of co-condensed methylene carbons accounts for over 40%, indicating the MDMUF co-condensation reactions were much more competitive than the self-condensations. The formation of reactive carbocation intermediate was proposed to rationalize the results.

Introduction: Laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy is gaining popularity as a treatment for choledochal cyst (CDC) in children. However, the learning curve for this challenging laparoscopic procedure has not been addressed. The aim of this study is to determine the characteristics of the learning curve of this procedure. This may guide the training in institutions currently not using this technique., Methods: A prospectively collected database comprising all medical records of the first 104 consecutive patients undergoing laparoscopic CDC excision and Roux-en-Y hepaticojejunostomy performed by one surgeon was studied. Multifactorial linear/logistic regression analysis was performed to identify patient-, surgeon-, and procedure-related factors associated with operating times, rates of adverse event, and length of postoperative stay., Results: Cumulative sum analysis demonstrated a learning curve for laparoscopic choledochal cyst excision of 37 cases. Comparing the early with the late experiences (37 vs. 67 cases), the surgeon-specific outcomes significantly improved in terms of operating times (352 vs. 240 min; P < 0.001), postoperative complication rate (13.5 vs. 1.5 %; P = 0.02), and the length of hospital stay (9.4 vs. 7.8 days; P = 0.01). After multivariate analyses, independent predictors of operating times included the completion of the learning curve (CLC) (OR 0.68, 95 % CI 0.63-0.73) and adhesion score (OR middle 1.25, 95 % CI 1.08-1.45; OR high 1.40, 95 % CI 1.20-1.62; compared with the low score); significant predictors of perioperative adverse outcomes were CLC (OR 0.07, 95 % CI 0.02-0.34) and comorbidities prior to the surgery (OR 30.65, 95 % CI 1.71-549.63). The independent predictors of length of postoperative stay included CLC, preoperative comorbidities, and perioperative adverse events., Conclusions: CLC for laparoscopic choledochal cyst excision is 37 cases. After CLC, not only the operative time is reduced, the complications, adverse results, and the length of hospital stay all decreased significantly. The learning curve can be used as the basis for performance guiding the training., Competing Interests: Compliance with ethical standards Disclosures Zhe Wen, Huiying Liang, Jiankun Liang, Qifeng Liang, and Huimin Xia have no conflicts of interest or financial ties to disclose.

The mechanisms for the base-catalyzed condensation reactions in phenol-formaldehyde resin synthesis were investigated by using the density functional theory method. The structures of the intermediates and transition states, as well as the potential energy barriers of the involved reactions, were obtained. The hypothesis of quinine methide (QM) formation was theoretically confirmed. Two mechanisms were identified for QM formation, namely E1cb (elimination unimolecular conjugate base) and water-aided intra-molecular water elimination. The latter is energetically more favorable and is proposed for the first time in this work. Based on the QM mechanism, the condensation should be a unimolecular reaction because the following condensation between an ionized species (dissociated phenol or hydroxymethylphenol) with QM is much faster. The previously proposed S N 2 condensation mechanism was found to be not competitive over the QM mechanism due to a much higher energy barrier. The condensation reaction between neutral phenol or hydroxymethylphenol and QM was also found to be possible. The energy barrier of this reaction is close to or higher than that of QM formation. Therefore, the overall condensation reaction may appear to be bimolecular if such a reaction is incorporated. The theoretical calculations in this work rationalized the discrepant results reported in previous kinetics studies well.

The reactions of di-hydroxymethylurea with phenol under alkaline (pH = 10), weak (pH = 6) and strong acidic (pH = 2) conditions were investigated via the 13 C-NMR method. Based on the proposed reaction mechanisms, the variations of the structures of different condensed products were analyzed and the competitive relationship between self- and co-condensation reactions was elucidated. The required experimental conditions for co-condensations were clearly pointed out. The main conclusions include: (1) the self-condensation between urea formaldehyde (UF) or phenol formaldehyde (PF) monomers were dominant while the co-condensations were very limited under alkaline conditions. This is because the intermediates produced from urea, methylolurea and phenol are less reactive in co-condensations with respect to self-condensations; (2) under weak acidic conditions, the self-condensations occurred exclusively among the UF monomers. The co-condensation structures were not observed; and (3) the co-condensations became much more competitive under strong acidic conditions as the relative content of the co-condensed methylenic carbon accounts for 53.3%. This result can be rationalized by the high reactivity of the methylolphenol carbocation intermediate toward urea and methylolurea. The revealed reaction selectivity and mechanisms may also be applied to the synthesis of those more complex co-condensed adhesives based on natural phenolic and amino compounds.

The survival and colonization of tumor cells at new locations involve a variety of complex genetic, epigenetic, and microenvironmental factors. TRIM24 was originally named transcription intermediary factor 1-alpha (TIF1α), which was associated with cellular proliferation and was an oncogene in tumor development. Here we provide the first evidence of the expression profile and clinicopathological significance of TRIM24 in patients with hepatocellular carcinoma (HCC). Immunohistochemistry was employed to determine the expression level of TRIM24 in HCC tissues and noncancerous liver tissues. Elevated TRIM24 level was found in 61.4% HCC samples (51/83) correlating with AFP (P = 0.036), poor differentiation (P = 0.004), intrahepatic metastasis (P = 0.004), recurrence (P = 0.000006), and shorter tumor-free survival time (P = 0.002). Small interfering RNA induced down-regulation of TRIM24 promoted apoptosis in HCC cell line HepG2. Moreover, western blotting analysis revealed that knockdown of TRIM24 increased the protein levels of p53, Bax, and Caspase-8, and decreased Bcl-2, Survivin, Cyclin D1, and CDK4. Depletion of TRIM24 decreased Snail, Slug, β-catenin, and Vimentin, and increased E-cadherin expression, which suggested the involvement of TRIM24 in EMT. These results indicated that TRIM24 plays an important role in the pathogenesis of human HCC.

Objective: To investigate the surgical techniques and appropriate perioperative management for ensuring successful orthotopic liver transplantation (ROLT) in rats., Methods: Based on the double-cuff technique of Kamada, we modified the surgical techniques of separation, perfusion and cold preservation of the donor liver, shearing and anastomosis of the suprahepatic vena cava with optimized postoperative infusion protocols and animal care., Results: Two hundred and seventy rats underwent ROLT and a learning curve of the success rate was built to reflect the improvement of techniques. The learning curve showed steep improvements over the exploration stage, breakthrough stage and maturation stage, and the success rates increased sharply over time (0%, 71.1%, and 94.5%, respectively) until finally reaching over 90%. The shearing and anastomosis of the suprahepatic vena cava remained the most critical and difficult techniques in ROLT modeling., Conclusion: Proficient microsurgical techniques and meticulous nursing can reduce postoperative complications, enhance operational success rate and extend the survival time after ROLT.

Objective: To investigate the expression and clinical significance of Nusap1 in hepatical carcinoma., Methods: The expression of Nusap1 protein in 61 specimens of hepatical carcinoma was examined by immunohistochemistry. Based on the levels of Nusap1 expression, the 61 specimens were divided into a high Nusap1 expression group and a low Nusap1 expression group. The correlation between Nusap1 expression with clinicopathologic features and prognosis of hepatical carcinoma was analyzed., Results: The rate of high Nusap1 expression was 54.1% in hepatical carcinoma. The rate of high Nusap1 expression was 21.3% in noncarcinoma, with significant difference between the 2 groups (P<0.01).Nusap1 overexpression had significant correlation with histological differentiation, tumor size, liver cirrhosis, lymphatic metastasis, tumor thrombi and early recurrence (P<0.05), but not with sex, age, AFP level, tumor number, TNM classification and tumor encapsulation (P>0.05). Survival analysis suggested that the 6 month and 12 month noncarcinoma survival rate was significantly lower in the high Nusap1 expression group [33.3% (11/33), 17.9% (5/33)] than that in the low Nusap1 expression group [89.3% (25/28), 53.6% (15/28); P<0.005]., Conclusion: Nusap1 is overexpressed in hepatical carcinoma and is a valuable prognostic factor for hepatical carcinoma.