Binding of interleukin-1 receptor antagonist to cholinergic receptor muscarinic 4 promotes immunosuppression and neuroendocrine differentiation in prostate cancer.

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses. Our research investigates the oncogenic role of IL1RN in PCa, particularly its interactions with muscarinic acetylcholine receptor 4 (CHRM4), and its involvement in driving immunosuppressive pathways and M2-like macrophage polarization within the PCa TME. We demonstrate that following androgen deprivation therapy (ADT), the IL1RN-CHRM4 interaction in PCa activates the MAPK/AKT signaling pathway. This activation upregulates the transcription factors E2F1 and MYCN, stimulating IL1RN production and creating a positive feedback loop that increases CHRM4 abundance in both PCa cells and M2-like macrophages. This ADT-driven IL1RN/CHRM4 axis significantly enhances immune checkpoint markers associated with neuroendocrine differentiation and treatment-resistant outcomes. Higher serum IL1RN levels are associated with increased disease aggressiveness and M2-like macrophage markers in advanced PCa patients. Additionally, elevated IL1RN levels correlate with better clinical outcomes following immunotherapy. Clinical correlations between IL1RN and CHRM4 expression in advanced PCa patients and neuroendocrine PCa organoid models highlight their potential as therapeutic targets. Our data suggest that targeting the IL1RN/CHRM4 signaling could be a promising strategy for managing PCa progression and enhancing treatment responses.

Immunosuppressive role of BDNF in therapy-induced neuroendocrine prostate cancer.

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT-driven LIF/LIFR signaling induces brain-derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration-resistant PCa (CRPC) and a positive correlation with programmed death-ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.

Single-Port Laparoscopic Extraperitoneal Repair of Pediatric Inguinal Hernias and Hydroceles by Using Hernia Crochet Needle With a Cannula.

PURPOSE: Numerous modifications laparoscopic techniques have mushroomed in recent years. Here we describe a modified technique of extracorporeal ligation of processus vaginalis in children using a hernia crochet needle with a cannula. METHODS: Processus vaginalis repair was carried out on patients diagnosed with inguinal hernia or hydroceles using this novel technique between June 2021 and June 2022. The processus vaginalis was closed extracorporeally using a hernia crochet needle with a cannula. In the presence of patent processus vaginalis, the same procedure would be performed on the contralateral side. The primary outcomes was the safety and efficiency of this modified procedure, and the secondary outcomes was the post operative complications. RESULTS: A total of 212 (165 inguinal hernia and 47 hydroceles) children were corrected by this novel technique. The mean operation time was 27.49 min for unilateral inguinal hernia cases and 36.55 min for bilateral cases. The unilateral hydrocele median operation time was 27.83 min and that for the bilateral cases was 37.30 min. During the mean of 10.92 months of follow-up, there was only a boy subject to a metachronous contralateral occurrence of hernia 10 months after surgery, and no other complications (knot reactions, testicular atrophy, postoperative hydrocele or iatrogenic) have been observed yet. CONCLUSION: This study shown a unique procedure with using a hernia crochet needle with a cannula to be simple, safe, and effective in managing inguinal hernias and hydroceles in the pediatric population.

Treatment of filtration bleb dysfunction after glaucoma surgery by needle revision of filtration bleb combined with conbercept.

Filtration surgery (Trabeculectomy) is the main treatment for glaucoma. The scarring of the filtration bleb and obstruction of the outflow of aqueous humor through the filtration channel are the main reasons of the surgery failure. The objective of this study was to determine the clinical efficacy of needle revision of filtration blebs combined with subconjunctival injection of conbercept on the functional bleb formation in glaucoma patients with eye pressure out of control after trabeculectomy. A total of 48 eyes with poor filtration bleb function after trabeculectomy for glaucoma were treated with needle revision of filtration bleb combined with subconjunctival injection of conbercept. After the treatment, the patients were followed up for 3 months during which visual acuity, intraocular pressure, slit lamp and ultrasound biomicroscope examinations were performed. Intraoperative and postoperative complications were recorded. The visual acuity and intraocular pressure were significantly improved after the needle revision of filtration blebs. Among the 48 eyes, 39 eyes still had functional blebs at the end of the follow-up period, and filtration blebs failed in 9 eyes 2 to 8 weeks after the removal of the needle. The survival rate of filtration blebs at 3 months after needle revision was (79.06 ±â€…3.42%), and 81.25% (39/48) of the eyes showed good formation rate of functional bleb at the last follow-up. Three months after needle revision, there was local scar formation in some filtration blebs. Part of the filtration blebs showed mild thickening of the local subconjunctival tissue, and the filtration bleb was slightly raised and diffuse, showing a multi-cavity and thin-walled shape in some blebs. Ultrasound biomicroscopy examination showed relative structural manifestations. Subconjunctival hemorrhage occurred in 43 patients during and after the operation. Low intraocular pressure occurred in 8 patients with the lowest pressure of 5 mm Hg. Choroidal edema was observed in 3 patients. Five patients had intraoperative conjunctival hemorrhage in the anterior chamber, and hyphema occurred. All complications were self-limited and resolved without surgical intervention. Needle revision of filtration bleb combined with anti-VEGF drugs is a safe and effective method for the treatment of filtration bleb dysfunction after surgery of glaucoma.

Intervention effects and related mechanisms of glycyrrhizic acid on zebrafish with Hirschsprung-associated enterocolitis.

BACKGROUND: The prevention and treatment of Hirschsprung-associated enterocolitis (HAEC) is a serious challenge in pediatric surgery. Exploring the mechanism of HAEC is conducive to the prevention of this disease. AIM: To explore the possible mechanism of glycyrrhizic acid (GA) and its therapeutic effect on HAEC. METHODS: We developed a model of enteritis induced by trinitrobenzenesulfonic acid (TNBS) in zebrafish, and treated it with different concentrations of GA. We analyzed the effect of GA on the phenotype and inflammation of zebrafish. RESULTS: After treatment with TNBS, the area of the intestinal lumen in zebrafish was significantly increased, but the number of goblet cells in the intestinal lumen was significantly reduced, but these did not increase the mortality of zebrafish, indicating that the zebrafish enteritis model was successfully developed. Different concentrations of GA protected zebrafish with enteritis. In particular, high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area, increased the number of goblet cells in the intestinal lumen, and reduced the levels of interleukin (IL)-1ß and IL-8. CONCLUSION: GA significantly reduced the intestinal luminal area, increased the number of intestinal goblet cells, and decreased IL-1ß and IL-8 in zebrafish, and is important for prevention and control of HAEC.

Development and validation of prognostic risk prediction models for hepatocellular carcinoma patients treated with immune checkpoint inhibitors based on a systematic review and meta-analysis of 47 cohorts.

Objective: To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis. Methods: We searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients. Results: A total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models. Conclusion: Based on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model's selected indicators are easily obtainable, making them suitable for further application in clinical practice.

Anorectal malformation combined with Hirschsprung's disease: a case report.

Anorectal malformation (ARM) and Hirschsprungs disease (HSCR) are frequently associated with other congenital malformations, but rarely with one another. We describe the case of a child with intermediate anorectal malformation who underwent ARM correction. This child experienced recurrent postoperative symptoms, including intestinal obstruction, nutrition intolerance, and weight loss. The child was diagnosed with Hirschsprung's disease by colon barium contrast and pathological findings from a rectal biopsy, and subsequently underwent pull -through procedure after conservative treatment failed. After six months of postoperative follow-up, the patient still experiences occasional episodes of enteritis, but the symptoms are substantially less severe than they were before surgery, and the patient's weight is slowly increasing. We described a case of a child who had ARM combined with HSCR. Although the association between ARM and HSCR is uncommon, severe constipation or enteritis following complete correction of ARM in the absence of anal stricture should prompt consideration for HSCR. Before the second stage of ARM surgery, pay close attention to the barium enema examination, as an abnormal shape may indicate the presence of HSCR.

Swin Unet3D: a three-dimensional medical image segmentation network combining vision transformer and convolution.

BACKGROUND: Semantic segmentation of brain tumors plays a critical role in clinical treatment, especially for three-dimensional (3D) magnetic resonance imaging, which is often used in clinical practice. Automatic segmentation of the 3D structure of brain tumors can quickly help physicians understand the properties of tumors, such as the shape and size, thus improving the efficiency of preoperative planning and the odds of successful surgery. In past decades, 3D convolutional neural networks (CNNs) have dominated automatic segmentation methods for 3D medical images, and these network structures have achieved good results. However, to reduce the number of neural network parameters, practitioners ensure that the size of convolutional kernels in 3D convolutional operations generally does not exceed [Formula: see text], which also leads to CNNs showing limitations in learning long-distance dependent information. Vision Transformer (ViT) is very good at learning long-distance dependent information in images, but it suffers from the problems of many parameters. What's worse, the ViT cannot learn local dependency information in the previous layers under the condition of insufficient data. However, in the image segmentation task, being able to learn this local dependency information in the previous layers makes a big impact on the performance of the model. METHODS: This paper proposes the Swin Unet3D model, which represents voxel segmentation on medical images as a sequence-to-sequence prediction. The feature extraction sub-module in the model is designed as a parallel structure of Convolution and ViT so that all layers of the model are able to adequately learn both global and local dependency information in the image. RESULTS: On the validation dataset of Brats2021, our proposed model achieves dice coefficients of 0.840, 0.874, and 0.911 on the ET channel, TC channel, and WT channel, respectively. On the validation dataset of Brats2018, our model achieves dice coefficients of 0.716, 0.761, and 0.874 on the corresponding channels, respectively. CONCLUSION: We propose a new segmentation model that combines the advantages of Vision Transformer and Convolution and achieves a better balance between the number of model parameters and segmentation accuracy. The code can be found at https://github.com/1152545264/SwinUnet3D .

Effect of modified transanal Soave assisted by laparoscopy in the treatment of Hirschsprung's disease in children and its influencing factors.

OBJECTIVE: To investigate the effect of modified transanal Soave assisted by laparoscopy in children with Hirschsprung's disease (HD). METHODS: The clinical data of 120 children with Hirschsprung's disease admitted to Fujian Children's Hospital from January 2018 to November 2021 were retrospectively analyzed. Based on the surgical methods, 58 children treated with modified transanal Soave were regarded as the modified group and 62 children treated with modified transanal Soave assisted by laparoscopy were divided into the laparoscopic group. The operative indexes, anal function, quality of life and perianal pressure 6 months after surgery, complications within 1 month after surgery, and recovery within 6 months after surgery of the two groups were compared. The risk factors influencing the postoperative recovery of hirschsprung's disease in children were analyzed by univariate and logistic regression analysis. RESULTS: The operation time, intraoperative blood loss, length of hospital stay and gastrointestinal recovery time in the laparoscopic group were lower than those in modified group (P < 0.05). The excellent and good rate of postoperative anal function in laparoscopic group was 87.10%, which was higher than that in modified group (68.97%) (P < 0.05). The proportion of patients with good quality of life in laparoscopic group (90.32%) was higher than that in modified group (74.14%) (P < 0.05). The anal resting pressure and systolic pressure in laparoscopic group were lower than those in modified group (all P < 0.05). The total complication rate of laparoscopic group (6.45%) was lower than that of modified group (22.41%) (P < 0.05). After 6 months, 64 cases (53.33%) were cured and 56 cases (46.67%) were not. After univariate analysis, there were statistically significant differences in enteritis, abdominal distension, and anastomotic stenosis between cured children and uncured children (all P < 0.05). There was no significant difference in other factors (P > 0.05). Logistic regression analysis showed that enteritis, abdominal distension and anastomotic stenosis were the risk factors affecting the recovery of hirschsprung's disease in children (all P < 0.05). CONCLUSIONS: Modified transanal Soave assisted by laparoscopy can improve anal function and quality of life, relieve anal pressure, and have a low complication rate. Enteritis, abdominal distension, and anastomotic stenosis are the factors affecting the recovery of Hirschsprung's disease in children.

Outcome of Santulli enterostomy in patients with immaturity of ganglia: single institutional experience from a case series.

BACKGROUND: Immaturity of ganglia (IG) is an extremely rare disease and always requires surgical intervention in the neonatal period, but without guidelines to choose the ideal enterostomy procedure, the timing of stoma closure remains controversial. The aim of this study was to report our experience using Santulli enterostomy for the treatment of nine infants diagnosed with IG. METHODS: Patients who underwent Santulli enterostomy and were diagnosed with IG in our center between 2016 and 2021 were retrospectively studied. Temporary stoma occlusion and a 24-h delayed film of barium enema (BE) were performed to evaluate intestinal peristalsis function to determine the timing of stoma closure. The demographic data, clinical and radiological findings, stoma occlusion and stoma closure results were explored. RESULTS: A total of 9 infants underwent Santulli enterostomy and were diagnosed with IG postoperatively. Their median gestational age at birth was 36 weeks (range 31-42), and their median birth weight was 2765 g (range 1300-3400). All patients had symptom onset in the neonatal period, including abdominal distension and biliary vomiting. Eight patients showed obvious small bowel dilatation in the plain films, except for one patient's films that suggested gastrointestinal perforation with free gas downstream of the diaphragm. BE was performed in 6 patients, all of which had microcolons. The median age at operation was 3 days (range 1-23). Seven patients had an obvious transitional zone (TZ) during laparotomy, and the position of the TZ was 25-100 cm proximal above the ileocecal (IC) valve. Immature ganglion cells were present in the colon in 7 patients and the terminal ileum in 6 patients. The median age of successful stoma occlusion was 5 M (range 2-17) and 8 M (range 4-22) at ostomy closure. There was little or no barium residue in the 24-h delayed film of BE before stoma closure, and all patients were free of constipation symptoms during the follow-up. CONCLUSION: Santulli enterostomy appears to be a suitable and efficient procedure for IG, combined with temporary stoma occlusion and 24-h delayed film of BE to evaluate the recovery of intestinal peristalsis function.

Outcomes and comparations of pediatric surgery about choledochal cyst with robot-assisted procedures, laparoscopic procedures, and open procedures: A meta-analysis.

Background: Choledochal cysts (CC) are rare disorders characterized by congenital biliary dilatation of the intrahepatic or extrahepatic bile ducts and always relate to pancreaticobiliary maljunction. Robot-assisted surgery has been able to complete almost all pediatric endoscopic surgery nowadays. But evidence of the post-operative outcomes of robotic-assisted operation is limited, comparing with the laparoscopic operation and traditional open operation. The aim of this meta-analysis was to identify the advantages and deficiencies about robotic-assisted operation for CC. Methods: A meta-analysis of retrospective studies published in PUBMED, MEDLINE, Web of Science and China National Knowledge Infrastructure (CNKI). No date limit was used, with the last search on April 30, 2022. No publication restrictions or study design filters were applied. Results: Nine retrospective cohort studies with 1,395 patients [366 in the robotic-assisted operation group (RG), 532 in the laparoscopic operation group (LG) and 497 in the open operation group (OG)] were enrolled in our study. Subgroup analysis demonstrated the RG had significant longer operative time [standardized mean difference (SMD) = 1.59, 95% CI = (0.02, 3.16), P < 0.05], less blood loss [SMD = -1.52, 95% CI = (-2.71, -0.32), P < 0.05], shorter enteral feeding time [SMD = -0.83, 95% CI = (-1.22, -0.44), P < 0.001], shorter time to stay in the hospital [SMD = -0.81, 95% CI = (-1.23, -0.38), P < 0.001], fewer post-operative complications [Relative risk (RR) =1.09, 95% CI = (1.04, 1.13), P < 0.001] but higher expenses [SMD = 8.58, 95% CI = (5.27, 11.89), P < 0.001] than LG. While a significant older age [SMD = 0.46, 95% CI = (0.26, 0.66), P < 0.001], longer operative time [SMD = 3.96, 95% CI = (2.38, 5.55), P < 0.001] and shorter time to stay in the hospital [SMD = -0.93, 95% CI = (-1.62, -0.25), P < 0.05] than OG. Conclusions: Laparoscopic and robotic-assisted procedure are both safe and minimal invasive operational strategies. Robotic-assisted procedure may slowly surpass and has a trend to replace laparoscopy for its advantages. More experiences in robotic-assisted operation should be accumulated for the unexpected complexities, so as to be more stable in the younger age of children.

Laparoscopic-assisted Soave procedure for Hirschsprung disease: 10-year experience with 106 cases.

BACKGROUND: The purpose of this study was to summarize the clinical experience and 10 year follow-up results of laparoscopic assisted Soave procedure for the treatment of long-segment Hirschsprung disease (HD). METHODS: From January 2010 to February 2020, 106 children with long-segment HD participated in this study. The laparoscopic-assisted Soave procedure was performed for the treatment of long-segment HD. The follow-up time was two weeks, one month, and three months after the operation, and then every six months to one year. RESULTS: The operation was successful for all 106 children. All patients were discharged 5-7 days after the operation. The median time in surgery was 150 (100-190) minutes, and the median volume of bleeding was 6 (3-10) ml. The short-term postoperative daily defecation frequency was 4-11 times, 3-7 times within 6 months, and 2-3 times after 6-12 months. Postoperative complications included anastomotic leakage in two cases, perianal dermatitis in 13 cases, anastomotic stenosis in four cases, adhesive bowel obstruction in two cases, enterocolitis in 16 cases, soiling in 11 cases, and constipation recurrence in three cases. CONCLUSIONS: The laparoscopic-assisted Soave procedure is a safe and effective surgical method for treating long-segment HD, and it causes little trauma or bleeding and has a fast postoperative recovery. Yet some complications may occur. Preoperative diagnosis, intraoperative and postoperative standardized processing can reduce the postoperative complications.

The diagnosis and treatment of retrograde intussusception: a single-centre experience.

BACKGROUND/PURPOSE: To investigate the clinical manifestations, treatments of retrograde intussusception and summarize the experience. METHODS: Children with retrograde intussusception treated in our hospital from January 2011 to January 2021 were retrospectively analysed. Demographics, clinical manifestations, preoperative colour Doppler ultrasound (CDU) findings, findings during surgery and follow-up results were collected. RESULTS: A total of 4719 cases of intussusception were treated in our department, including 12 cases of retrograde intussusception (0.25%). There were 8 males and 4 females.The age ranged from 4.1 to 14.3 months, with an average of (8.3 ± 2.8) months.; The weight ranged from 5.5 to 12.6 kg, with an average of (9.4 ± 2.3) kg; The onset time ranged from 6 to 15 h, with an average of (10.0 ± 2.4) h. All the children received CDU examination before surgery, and in one case, the possibility of 2 intussusception masses was considered. Emergency surgical exploration was performed after the failure of air enema reduction. During the operation, multiple types of intussusception were found (coincidence of anterograde and retrograde intussusception). The pattern of anterograde intussusception was all ileo-ileo-colic variety and the retrograde intussusception was proximal sigmoid colon into descending colon. All the children were successfully reduced by manual reduction without intestinal necrosis or intestinal malformation. All children were discharged 6-7 days after surgery, and had no recurrence after 3-6 months of follow-up. CONCLUSIONS: Retrograde intussusception is easily misdiagnosed before surgery. During air enema, if the intussusception mass was fixed and did not move with increasing pressure, we should be aware of the possibility of retrograde intussusception, and the enema pressure should not be too large to avoid intestinal perforation. If the intraoperative position of the intussusception mass was not consistent with that of the preoperative enema, it was recommended to use bimanual examination to explore whether there was still a mass in the abdominal cavity to avoid misdiagnosis.

General versus general anaesthesia combined with caudal block in laparoscopic-assisted Soave pull-through of Hirschsprung disease: a retrospective study.

BACKGROUND: Caudal block is one of the most preferred regional anesthesia for sub-umbilical region surgeries in the pediatric population. However, few studies are available on caudal block performed in laparoscopic-assisted Soave pull-through of Hirschsprung disease (HD). We aimed to compare general anesthesia (GA) and general anesthesia combined with caudal block (GA + CA) in laparoscopic-assisted Soave pull-through of HD. METHODS: A retrospective review was performed in children with HD operated in our hospital between 2017 and 2020. Patients were divided into the GA and GA + CA group. The primary outcome was the duration of operation, and secondary outcomes included intraoperative hemodynamic changes, the Face, Legs, Activity, Cry, Consolability (FLACC) scale, dose of anesthetics, and incidence of side effects. RESULTS: A total of 47 children with HD were included in the study, including 20 in the GA group and 27 in the GA + CA Group. The two groups were similar in age, gender, weight and type of HD (P > 0.05). The GA + CA group had significantly shorter duration of operation (especially the transanal operation time) (median 1.20 h vs. 0.83 h, P < 0.01) and recovery time (mean 18.05 min vs. 11.89 min, P < 0.01). The mean doses of sufentanil and rocuronium bromide during the procedure and FLACC scores at 1 h and 6 h after surgery were also lower in the GA + CA group (p < 0.01). The hemodynamic changes in the GA + CA group were more stable at time of t2 (during transanal operation) and t3 (10 min after transanal operation), but there was no significant difference in the incidence of postoperative side effects between the two groups (P = 1.000). CONCLUSION: General anesthesia combined with caudal block can shorten the duration of operation, and provide more stable intraoperative hemodynamics and better postoperative analgesia.

Laparoscopic Soave procedure for long-segment Hirschsprung's disease - single-center experience.

INTRODUCTION: Hirschsprung's disease (HD) is one of the most common and severe diseases treated in pediatric surgery. Since the introduction of the laparoscopic technique into pediatric surgery, laparoscopic-assisted radical surgery for HD has demonstrated unique advantages. Long-segment and total-colon HD are the best indications for laparoscopic-assisted surgery. AIM: To summarize clinical experience of the laparoscopic Soave procedure for long-segment HD in a single center. MATERIAL AND METHODS: The data of children with long-segment HD who underwent the laparoscopic Soave procedure in our department from January 2013 to May 2018 were reviewed. The clinical features, surgical procedures and follow-up results were summarized and analyzed. RESULTS: Thirty-one children underwent the laparoscopic Soave procedure; none of them were converted to open surgery. The average hospitalization time was 8.7 days after the operation, and no immediate postoperative complications occurred. There was no recurrence of constipation. Six (19.3%) cases were complicated with HD associated enterocolitis in the first 3 months postoperatively; 5 (16.1%) cases had soiling in the first year. There were 0 cases of adhesive bowel obstruction, 0 cases of anastomotic stenosis, and 0 cases of constipation. CONCLUSIONS: A small volume centre may achieve satisfactory results for long-segment HD. The laparoscopic Soave procedure is a minimally invasive, safe and effective treatment.

Oyster Versatile IKKα/ßs Are Involved in Toll-Like Receptor and RIG-I-Like Receptor Signaling for Innate Immune Response.

IκB kinases (IKKs) play critical roles in innate immunity through signal-induced activation of the key transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs). However, studies of invertebrate IKK functions remain scarce. In this study, we performed phylogenetic analysis of IKKs and IKK-related kinases encoded in the Pacific oyster genome. We then cloned and characterized the oyster IKKα/ß-2 gene. We found that oyster IKKα/ß-2, a homolog of human IKKα/IKKß, responded to challenge with lipopolysaccharide (LPS), peptidoglycan (PGN), and polyinosinic-polycytidylic acid [poly(I:C)]. As a versatile immune molecule, IKKα/ß-2 activated the promoters of NF-κB, TNFα, and IFNß, as well as IFN-stimulated response element (ISRE)-containing promoters, initiating an antibacterial or antiviral immune state in mammalian cells. Importantly, together with the cloned oyster IKKα/ß-1, we investigated the signal transduction pathways mediated by these two IKKα/ß proteins. Our results showed that IKKα/ß-1 and IKKα/ß-2 could interact with the oyster TNF receptor-associated factor 6 (TRAF6) and that IKKα/ß-2 could also bind to the oyster myeloid differentiation factor 88 (MyD88) protein directly, suggesting that oyster IKKα/ßs participate in both RIG-I-like receptor (RLR) and Toll-like receptor (TLR) signaling for the reception of upstream immune signals. The fact that IKKα/ß-1 and IKKα/ß-2 formed homodimers by interacting with themselves and heterodimers by interacting with each other, along with the fact that both oyster IKKα/ß proteins interacted with NEMO protein, indicates that oyster IKKα/ßs and the scaffold protein NEMO form an IKK complex, which may be a key step in phosphorylating IκB proteins and activating NF-κB. Moreover, we found that oyster IKKα/ßs could interact with IRF8, and this may be related to the IKK-mediated activation of ISRE promotors and their involvement in the oyster "interferon (IFN)-like" antiviral pathway. Moreover, the expression of oyster IKKα/ß-1 and IKKα/ß-2 may induce the phosphorylation of IκB proteins to activate NF-κB. These results reveal the immune function of oyster IKKα/ß-2 and establish the existence of mollusk TLR and RLR signaling mediated by IKKα/ß proteins for the first time. Our findings should be helpful in deciphering the immune mechanisms of invertebrates and understanding the development of the vertebrate innate immunity network.

Early complications after laparoscopic resection of choledochal cyst.

PURPOSE: To investigate the causes and treatments of early complications involving laparoscopic radical resection of choledochal cyst and summarize the experience. METHODS: Children with choledochal cyst treated by laparoscopy in the Department of Pediatric Surgery, Fujian Provincial Maternity and Children's Hospital, and Guangzhou Women and Children's Medical Centre, from March 2016 to May 2018, were retrospectively analysed. Demographics, causes and treatments of early complications, liver function analysis and ultrasonography were collected. RESULTS: In total, 231 cases were included; 204 were Type I (156 Type Ia and 46 Type Ic) and 27 were Type IV. No mortality was observed, and 224 cases were successfully laparoscopically operated, while 7 cases were converted to open surgery. Fifteen cases of postoperative developed biliary fistula. There were jejunal Roux loop obstruction in 2 cases and multiple intussusception, anastomotic stenosis after hepaticojejunostomy, residual of choledochal cyst and pancreatic fistula in one each. Patients were followed up ranging from 4 months to 48 months (12.6 ± 0.3 months on average). Postoperative ALT, AST, GGT, TBIL and DBIL all returned to normal during this time. Ultrasonography indicated 5 cases of widened Glisson's sheath and 1 case of intrahepatic hyperdense shadow. CONCLUSION: Early complications of laparoscopic radical resection of choledochal cyst can be minimized by properly managing preoperative indications and contraindications, carefully interpreting the magnetic resonance cholangiopancreatography results and accumulating experience by the surgeons.

Pathological process of liver sinusoidal endothelial cells in liver diseases.

Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix, which is closely related to liver sinusoidal endothelial cells (LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor, which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein, we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.

Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response.

BacMam is an insect-derived recombinant baculovirus that can deliver genes into mammalian cells. BacMam vectors carrying target genes are able to enter a variety of cell lines by endocytosis, but the level of expression of the transgene depends on the cell line and the state of the transduced cells. In this study, we demonstrated that the DNA damage response (DDR) could act as an alternative pathway to boost the transgene(s) expression by BacMam and be comparable to the inhibitors of histone deacetylase. Topoisomerase II (Top II) inhibitor-induced DDR can enhance the CMV-IE/enhancer mediated gene expression up to 12-fold in BacMam-transduced U-2OS cells. The combination of a Top II inhibitor, VM-26, can also augment the killing efficiency of a p53-expressing BacMam vector in U-2OS osteosarcoma cells. These results open a new avenue to facilitate the application of BacMam for gene delivery and therapy.

[Cloning and expression of cysteine synthase gene from Polygonum sibiricum Laxm.].

Cysteine synthase is a key enzyme for restricting plant cysteine synthesis. Cysteine synthase gene, designated PcCSase1 (GenBank accession no. EU597481), was successfully isolated from Polygonum sibiricum Laxm. by RACE technique. This gene was 1 260 bp in full-length and encoded a peptide of 382 amino acids. Based on bioinformatic analysis, PcCSase1 is a cytoplasm cysteine synthesis and contains a 16 amino-terminal (N-terminal) signal peptide, which led the PcCSase1 to go to the cytoplasm. The results obtained through homologous sequence analysis indicated that PcCSase1 mature protein was highly conserved in plants, which shared approximate 90% in the amino acid sequence. Expression analysis by RT-PCR showed that PcCSase1 gene was expressed in leaf, stem and root with the largest expression in leaf. Under 3% NaHCO3 stress, the largest expression of PcCSase1 gene was detected in leaf, stem and root at the second day following stress. PcCSase1 gene was inserted into pYES2 and transformed into yeast cells (Saccharomyces cerevisiae). The contents of the glutathione in the recombinant yeast and the cysteine in the medium were increased. INVSc1-pYES2-PcCSase1 was more tolerant to salt treatment than INVSc1-pYES2 and the former survival rate was higher than that of the later under the stress of 10% NaHCO3 and 5 mol/L NaCl. These results proved that PcCSase1 gene may confer high salt-tolerance.