Human Liver Organoids to Predict the Outcome of Kasai Portoenterostomy.

BACKGROUND: Kasai portoenterostomy (KPE) remains the primary intervention for biliary atresia (BA), but its outcomes are highly variable. Reliable prognostic biomarkers remain elusive, complicating the management and prediction of postoperative progression. METHOD: Liver biopsies from BA patients taken at and after KPE (post-KPE) were used to generate organoids for RNA-sequencing analysis. Control organoids were derived from non-BA livers. Differential gene expression and enrichment analyses were performed to assess post-KPE transcriptomic changes between native liver survivors (NLS) and patients who eventually became liver transplant recipients (LTR). RESULTS: Organoid datasets: 70 from liver biopsies at KPE (10 patients), 112 from post-KPE livers (13 livers; 12 patients), and 47 from control livers (9 patients). At KPE, BA organoids displayed mainly hepatocyte expression, a trait notably reduced in control organoids. Similarly, post-KPE organoids from NLS revealed a significant decrease in hepatocyte expression features and an overall increase in cholangiocyte expression features. A similar hepatocyte-to-cholangiocyte expression transition was evidenced in paired liver organoids (at- and post-KPE) generated from an NLS. In contrast, post-KPE organoids from LTR maintained a high level of hepatocyte expression features. CONCLUSION: Our study demonstrated that an elevated expression of hepatocyte features in KPE organoids may indicate aberrant cholangiocyte development in BA livers. In contrast, a post-KPE hepatocyte-to-cholangiocyte expression transition in NLS may imply effective biliary recovery. The lack of this transition in LTR organoids indicates ongoing disease progression, highlighting the potential for organoid-based transcriptomic profiling to inform KPE success and guide BA management. LEVEL OF EVIDENCE: Level III.

Sprayable biomimetic double mask with rapid autophasing and hierarchical programming for scarless wound healing.

Current sprayable hydrogel masks lack the stepwise protection, cleansing, and nourishment of extensive wounds, leading to delayed healing with scarring. Here, we develop a sprayable biomimetic double wound mask (BDM) with rapid autophasing and hierarchical programming for scarless wound healing. The BDMs comprise hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylate (PLD) as top layer and hydrophilic gelatin methacrylate (GelMA) hydrogel as bottom layer, enabling swift autophasing into bilayered structure. After photocrosslinking, BDMs rapidly solidify with strong interfacial bonding, robust tissue adhesion, and excellent joint adaptiveness. Upon implementation, the bottom GelMA layer could immediately release calcium ion for rapid hemostasis, while the top PLD layer could maintain a moist, breathable, and sterile environment. These traits synergistically suppress the inflammatory tumor necrosis factor-α pathway while coordinating the cyclic guanosine monophosphate/protein kinase G-Wnt/calcium ion signaling pathways to nourish angiogenesis. Collectively, our BDMs with self-regulated construction of bilayered structure could hierarchically program the healing progression with transformative potential for scarless wound healing.

Outcomes of Children With Short Bowel Syndrome: Experiences in a Multidisciplinary Intestinal Rehabilitation Unit Over Two Decades.

BACKGROUND: Short bowel syndrome (SBS) is a rare but serious form of organ failure, and patients with SBS depend on total parenteral nutrition (PN) to maintain growth and development. The present study aimed to evaluate the experiences and outcomes of children with SBS managed by a multidisciplinary intestinal rehabilitation programme in a tertiary paediatric centre. METHODS: A retrospective single-centre analysis of all paediatric patients with a clinical diagnosis of SBS between 2001 and 2022 was performed. Clinical outcomes and their predictors were extracted and analysed. RESULTS: Of the 64 children included in the study, 43 (67%) had extensive necrotising enterocolitis. The median bowel length was 45 cm (interquartile range (IQR) = 18-65) and 18.9% (IQR = 10-28.5) of the expected length based on age. Over a mean follow-up period of 8.9 years, 57 patients (89%) survived, and 50 (78%) weaned off PN. The presence of intestinal failure-associated liver disease (IFALD) (OR = 6.375, p = 0.02) and patients managed before the introduction of fish oil-based PN in 2007 (OR = 5.895, p = 0.001) were significant predictors of mortality. There was an overall improvement in survival over time (p = 0.003). Ultrashort bowel length was not associated with significantly higher mortality (OR = 1.1, p = 0.65) but was a poor prognostic factor for weaning off PN (OR = 3.57, p = 0.004). Among all patients who weaned off PN, two had bowel lengthening procedures and one received a glucagon-like peptide 2 (GLP-2) analogue. CONCLUSIONS: A multidisciplinary intestinal rehabilitation programme offers a comprehensive approach for patients with SBS and has been shown to be effective with favourable outcomes. Improvements in the choice of PN and the development of new treatment strategies potentially improved the survival and enteral autonomy of SBS patients. LEVEL OF EVIDENCE: III.

Animal and organoid models to elucidate the anti-fibrotic effect of steroid on biliary atresia.

PURPOSE: We performed animal and organoid study to evaluate the anti-fibrotic effect of steroid on biliary atresia (BA) and the underlying patho-mechanism. METHODS: BA animal models were created by inoculation of mice on post-natal day 1 with rhesus rotavirus (RRV). They received either 20 µl phosphate-buffered saline (PBS) or steroid from day 21 to day 34. On day 34, their serum samples were collected for hormonal markers. Necrosis, fibrosis and CK 19 expression in the liver were evaluated. Liver organoids were developed and their morphology as well as bulk RNA sequencing data were analyzed. RESULTS: Twenty-four mice developed BA features after RRV injection and were equally divided into steroid and PBS groups. On day 34, the weight gain of steroid group increased significantly than PBS group (p < 0.0001). All mice in the PBS group developed liver fibrosis but only one mouse in the steroid group did. Serum bilirubin and liver parenchymal enzymes were significantly lower in steroid group. The morphology of liver organoids were different between the two groups. A total of 6359 differentially expressed genes were found between steroid group and PBS group. CONCLUSION: Based on our findings obtained from RRV-induced BA animal and organoid models, steroid has the potential to mitigate liver fibrosis in BA.

Functional Outcome in Patients With Anorectal Malformation With Recto-prostatic or Recto-bulbar Urethral Fistula and Comparison Between Different Surgical Approaches: A Multi-center Study.

PURPOSE: To analyze and compare the outcomes in patients with anorectal malformation with rectoprostatic and rectourethral fistula between laparoscopic-assisted anorectoplasty (LAARP) versus posterior sagittal anorectoplasty (PSARP). METHOD: We performed a retrospective review on all males with anorectal malformation (ARM) with recto-prostatic (ARM-RP) or recto-bulbar urethral fistula (ARM-RB) treated in five tertiary paediatric surgical centres in the past 25 years. Defecative function was assessed using the Krickenbeck classification and Kelly's score. Functional outcomes between patients with LAARP and PSARP were compared. RESULTS: There were a total of 136 males with ARM-RP and ARM-RB for analysis, among which 73 (53.7%) had ARM-RP and 63 (46.3%) had ARM-RB. The median age of the patients was 9.4 years (range 0.8-24.7 years) and the median age at operation was 0.4 years (0 day-3.1 years). 57 (41.9%) and 79 patients (58.1%) underwent PSARP and LAARP respectively. 34 patients (25%) had VACTERL association. 111 (81.6%) and 103 patients (75.7%) had sacral and spinal cord anomalies respectively. 19 patients (13.9%) eventually required Malone's Antegrade Continence Enema (MACE). For the comparison between PSARP and LAARP, no difference in Kelly scores (4.58 ± 1.63 versus 4.67 ± 1.36) was identified (p = 0.79). Logistic regression for voluntary bowel movement showed that VACTER association (p = 0.02) and fistula location (p = 0.01) were significant prognostic factors, whereas the operation approach (PSARP or LAARP) was not (p = 0.65). CONCLUSION: VACTERL association and fistula location were significant prognostic factors for voluntary bowel movement, and there appeared to be no significant difference in functional outcome between PSARP and LAARP. LEVEL OF EVIDENCE: IV.

Epidemiological changes in the pattern of children's traumatic injuries at Hong Kong emergency departments during the COVID-19 pandemic: a retrospective, single-institutional, serial and comparative study.

INTRODUCTION: Trauma is the leading cause of paediatric mortality and morbidity. Stay-home regulations for coronavirus disease 2019 (COVID-19) reportedly changed trauma severity, yet data from Hong Kong were lacking. This study examined Hong Kong's spectrum of paediatric trauma and addressed knowledge gaps concerning epidemiological changes during COVID-19. METHODS: Children with traumatic injuries who attended a tertiary trauma centre from January 2010 to March 2022 were included in this retrospective, cross-sectional study. We analysed demographic and clinical data and conducted unadjusted bivariate analyses of injury patterns before and after the pandemic. RESULTS: In total, 725 children attended the Accident and Emergency Department due to trauma, 585 before and 140 during COVID-19. The male-to-female ratio was 1.84:1. The 90-day trauma-related mortality was 0.7%. The overall Injury Severity Score was 3.52 ± 5.95. The paediatric trauma incidence was similar before and after social-distancing policies (both 5.8 cases monthly). Gender, ISS distribution, intensive care unit stay length, and hospital stay length values were similar (p > 0.05). Trauma call activation (8.4% vs. 5.7%, p = 0.002) and road traffic accidents (10.6% vs. 5.7%, p = 0.009) significantly decreased, yet younger-patient injuries (< 10 years old; 85.7% vs. 71%, p < 0.001), burns (28% vs. 45.7%, p < 0.001), and domestic injuries (65.5% vs. 85.7%, p < 0.001) significantly increased. No significant self-harm, assault, or abuse increases were found. CONCLUSIONS: The paediatric trauma incidences were similar before and during the pandemic. However, domestic and burn injuries significantly increased, highlighting the importance of injury prevention.

Comparison and clinical analysis of antibiotics and endoscopic injection for vesicoureteral reflux in children.

PURPOSE: This study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection. METHODS: The clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance. RESULTS: Fifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13-63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010). CONCLUSIONS: Endoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.

Comparative Outcomes of Single-Stage versus Two-Stage Laparoscopic Fowler-Stephens Orchidopexy: A Systematic Review snd Meta-Analysis.

INTRODUCTION: Intra-abdominal testis (IAT) remains a challenging and controversial subset within the management of cryptorchidism. While Fowler-Stephens orchidopexy (FSO) is still being advocated as the gold standard for the treatment of this entity, there is new and conflicting evidence on the comparative outcomes between single- or two-stage laparoscopic FSO (LFSO). The aim of the study is to investigate whether staging has benefits in children receiving LFSO. METHODS: We searched the PubMed, Medline, Embase, and Cochrane Trials databases for studies comparing single- with two-stage LFSO in children from January 1, 1995 to December 31, 2023. We assessed the identified studies for quality and performed a systematic review and meta-analysis in accordance with the Preferred Reporting of Systematic Reviews and Meta-Analyses. The main outcome measures examined were success rate (in terms of the scrotal position of the testis) and testicular atrophy, which were analyzed using fixed effect models. RESULTS: We included 17 eligible studies that involved a total of 499 operated testes. The overall success rates of single- and two-stage LFSO were 79.4 and 90.3%, respectively. The overall testicular atrophy rates of single- and two-stage LFSO were 17.3 and 11%, respectively. Fixed effect model analysis showed that two-stage LFSO is significantly superior to single-stage LFSO in overall success rate (odds ratio [OR: 2.57]; 95% confidence interval [CI]: 1.50-4.39, p = 0.0006) and testicular atrophy rate (OR: 0.48; 95% CI: 0.28-0.79, p = 0.004). There is no heterogeneity in the reports, and the funnel plot showed no publication bias. CONCLUSIONS: Two-stage LFSO remains the first choice of operation for children with a high IAT, with a significantly higher success rate and a lower testicular atrophy rate.

Cholestasis after Kasai operation predicts portal hypertension in native liver survivors of biliary atresia: a multicenter study.

PURPOSE: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). METHODS: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). CONCLUSIONS: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. LEVEL OF EVIDENCE: Level III.

Enhancing neonatal thoracoscopic surgical training with rabbit model.

Background: Thoracoscopy, which has an increasing role in the treatment of indexed neonatal surgical conditions, requires adequate training. To support this, the current study aimed to evaluate the feasibility and effectiveness of using live rabbit models in neonatal thoracoscopic skills training among paediatric surgeons. Methods: Following didactic lectures and demonstrations, the participants were given hands-on opportunities to perform thoracoscopic procedures. The feasibility and effectiveness of using live rabbit models in neonatal thoracoscopic skills training among paediatric surgeons were evaluated with pre-/post-course procedural confidence scores and a questionnaire. Results: This study included 13 paediatric surgeons-2 (15 %) males and 11 (85 %) females-who were evenly distributed. There were four basic surgical trainees, five higher surgical trainees and four fellows in paediatric surgery (mean surgical practice experience: 4.5 ± 3.7 years). Most had experience assisting paediatric (70 %) and neonatal (62 %) thoracoscopic surgery. Only 30 % had experience as the chief surgeon of paediatric thoracoscopic surgery, with none on neonates. Significant improvement was seen in procedural confidence as the assistant and chief surgeon of all procedures post-workshop. The surgeons rated the model positively. Conclusion: The procedural confidence level of paediatric surgeons improved significantly after workshop participation. This realistic and easily reproducible model can help perfect thoracoscopic skills. Therefore, its integration into paediatric surgical training would promote surgical skill proficiency and could improve surgeons' confidence in neonate operations.

Prophylactic anti-reflux procedure for children undergoing laparoscopic gastrostomy: Rethinking of the routine practice.

AIM: Laparoscopic gastrostomy is a frequently performed procedure in children requiring long-term enteral nutrition. The role of prophylactic anti-reflux surgery during gastrostomy placements is controversial. The current study aims to evaluate the role of prophylactic anti-reflux procedures during gastrostomy placement. METHODS: A retrospective single-center analysis of all children without reflux receiving laparoscopic gastrostomy from January 2005 through December 2021 was performed. Demographics and clinical outcomes were compared between patients receiving gastrostomy placement alone and patients receiving gastrostomy with prophylactic anti-reflux surgery. RESULTS: A total of 79 patients had a confirmed absence of reflux by a 24-h pH/impedance study before operation. Thirty-six of these patients underwent prophylactic anti-reflux surgery (PAR) while 43 received gastrostomy (PG) alone. The operative time and conversion rate were significantly higher in the PAR group (140.5 ± 67.5 vs. 80.2 ± 66.8 min, p = 0.0001 and 8.3% vs. 0%, p = 0.04). There were no major complications in either group. De novo reflux was detected in five patients (11.6%) in the PG group. None of these patients progressed to require anti-reflux surgery. CONCLUSION: The occurrence of de novo reflux after laparoscopic gastrostomy was low and could be managed without anti-reflux surgery. A routine pre-operative pH study is helpful for appropriate patient selection to avoid unnecessary anti-reflux surgery, which lengthens operative time and increases the conversion rate.

Quality of Life in Long-Term Survivors of Surgical Necrotizing Enterocolitis.

OBJECTIVE: This study evaluated the quality of life (QoL) in patients who have recovered from surgical necrotizing enterocolitis (NEC). METHODS: This is a cross-sectional study conducted in a tertiary centre and patients who have received surgery for NEC between 2000 and 2014 were invited to participate. The Pediatric Quality of Life Inventory Generic (PedsQL™) Core Scale Version 4.0 was used as the assessment tool. Values were reported as median (interquartile rage) and compared with age-matched controls. RESULTS: During the study period, 90 patients were eligible for the study and 29 patients have completed the survey. There was no gender difference and the median age was 10 years (9-13 years). Nine patients have suffered from short bowel syndrome (SBS) as a result of the surgery. For the QoL assessment, 17 participants have completed both parent proxy and child-rated survey; 11 completed the parent-rated survey and 1 completed child-rated survey only. The scores for parent-rated survey were - overall: 86.4 (70.7-92.7); physical: 95.3 (83.6-100) and psychosocial: 82.5 (66.3-90.4). The scores for child-rated survey were - overall: 82.1 (73.4-96.2); physical: 96.9 (90.6-99.2) and psychosocial: 81.7 (64.2-95.8). Regarding the impact of previous SBS on the QoL, there were no significant difference in the overall score for both parent proxy and child-rated survey (SBS-ve vs + ve) (parent-rated: 87.5 vs 85.3, p = 0.849; child-rated: 81.0 vs 88.0, p = 0.503). There were also no differences in physical and psychosocial assessments (parent-rated: [physical] 95.3 vs 95.3, p = 0.267; [psychosocial] 84.2 vs 80.0, p = 0.274; child-rated: [physical] 95.3 vs 96.9, p = 0.395; [psychosocial] 79.2 vs 87.5, p = 0.611). CONCLUSION: The QoL in long-term survivors of surgical NEC without major medical illnesses is comparable to normal population. However, they may have a lower psychosocial well-being that should be addressed. Previous history of SBS does not have a significant impact on the future QoL. LEVEL OF EVIDENCE: III.

Open Versus Thoracoscopic Repair of Congenital Diaphragmatic Hernia: A 19-Year Review in a Tertiary Referral Centre in Hong Kong.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a developmental defect that causes herniation of abdominal organs into the thoracic cavity with significant morbidity. Thoracoscopic repair of CDH is an increasingly prevalent yet controversial surgical technique, with limited long-term outcome data in the Asian region. The aim of this study was to compare open laparotomy versus thoracoscopic repair of CDH in paediatric patients in a major tertiary referral centre in Asia. METHODS: We performed a retrospective analysis of neonatal patients who had open laparotomy or thoracoscopic repair for CDH in our institution between July 2002 and November 2021. Demographic data, perioperative parameters, recurrence rates and surgical complications were analysed. RESULTS: 64 patients were identified, with 54 left sided CDH cases. 33 patients had a prenatal diagnosis and 35 patients received minimally invasive surgical repair. There was no significant difference between open and minimally invasive repair in recurrence rate (13 % vs 17 %, P = 0.713), time to recurrence (184 ± 449 days vs 81 ± 383 days, P = 0.502), or median length of ICU stay (11 ± 14 days vs 13 ± 15 days, P = 0.343), respectively. Gastrointestinal complications occurred in 7 % of neonates in the open group and none in the thoracoscopic group. Median follow-up time was 9.5 years. CONCLUSIONS: This study is a large congenital diaphragmatic hernia series in Asia, with long term follow-up demonstrating no significant difference in recurrence rate, time to recurrence or median length of ICU stay between open and minimally invasive repair, suggesting thoracoscopic approach is a non-inferior surgical option with avoidance of gastrointestinal complications compared to open repair. TYPE OF STUDY: Retrospective Cohort Study.

Analysing Factors Prolonging Hospital Stay After Excision of Choledochal Cyst-A Pathway Towards Enhanced Recovery After Surgery.

BACKGROUND: To evaluate factors affecting length of stay (LOS) after choledochal cyst resection in paediatric patients. METHODS: This was a retrospective study on patients operated between 2004 and 2021. Associations between clinical factors and LOS were evaluated by bivariate analysis, multiple regression, and equivalence test. RESULTS: Sixty-two patients were included. Twenty-four underwent hepaticoduodenostomy as biliary reconstruction. Five suffered from major complications. The median (25th-75th percentile) operation time was 279 (182-378) min. Median LOS, time to enteral feeding, and time to abdominal drain removal were 8(6-10), 2(1-3), and 5(4-7) days, respectively. Seven factors were found significantly associated with a shorter LOS in bivariate analysis and were included in multiple regression. It revealed that early abdominal drain removal (p < 0.001), early enteral feeding (p = 0.042), and the absence of major complications (p < 0.001) were significantly associated with shorter LOS. Equivalence test suggested that age and preoperative cholangitis had no practical effect on LOS. CONCLUSIONS: Early enteral feeding, early drain removal, and avoidance of major complications are associated with a shorter LOS.

The impact of pre-operative cholecystostomy on laparoscopic excision of choledochal cyst in paediatric patients.

PURPOSE: This aim of this study was to identify the pre-operative risk factors for conversion during laparoscopic excision of choledochal cyst in paediatric patients. METHODS: A retrospective single-centre study was carried out. All paediatric patients (< 18 years) who had undergone laparoscopic excision of choledochal cyst between 2004 and 2021 were reviewed. The outcome was conversion to open surgery and pre-operative factors that affected the conversion rate were analyzed. RESULTS: Sixty-one patients were included. Conversion was required in 24 cases (39.3%). There was no difference in the conversion rate between the first (before 2012, n = 30) and second (after 2012, n = 31) half of the series (36.7% vs. 42.0%, p = 0.674). Majority was type 1 cyst (86.8%) and the median cyst size was 4.6 cm (IQR: 2.2-6.4 cm). Antenatal diagnosis was available in 18 patients (29.5%). The median age at operation was 23.0 months (IQR: 8.0-72.0 months). Pre-operatively, 19 patients (31.1%) suffered from cholangitis and 5 (8.2%) of them required cholecystostomy. Comparing patients with successful laparoscopic surgery (L) and converted cases (C), there were no differences in the age at operation (p = 0.74), cyst size (p = 0.35), availability of antenatal diagnosis (p = 0.23) and cholangitic episodes (p = 0.40). However, a higher percentage of patients required cholecystostomy in the converted group (L vs. C = 2.7% vs. 16.7%, p = 0.05). Using logistic regression analysis, it was also a risk factor for conversion (OR = 3.5 [1.37-5.21], p = 0.05). CONCLUSION: Pre-operative cholecystostomy is a potential risk factor for conversion during laparoscopic excision of choledochal cyst in children.

Direct cellular reprogramming and transdifferentiation of fibroblasts on wound healing-Fantasy or reality?

Induced pluripotent stem cell (iPSC) technology is one of the de novo approaches in regeneration medicine and has led to new research applications for wound healing in recent years. Fibroblasts have attracted wide attention as the first cell line used for differentiation into iPSCs. Researchers have found that fibroblasts can be induced into different types of cells in variable mediums or microenvironments. This indicates the potential "stem" characteristics of fibroblasts in terms of direct cellular reprogramming compared with the iPSC detour. In this review, we described the morphology and biological function of fibroblasts. The stem cell characteristics and activities of fibroblasts, including transdifferentiation into myofibroblasts, osteogenic cells, chondrogenic cells, neurons, and vascular tissue, are discussed. The biological values of fibroblasts are then briefly reviewed. Finally, we discussed the potential applications of fibroblasts in clinical practice.

Silver nanoparticles promote osteogenic differentiation of mouse embryonic fibroblasts in vitro.

OBJECTIVE: This study investigated if silver nanoparticles (AgNps) could promote the proliferation and osteogenic differentiation of mouse embryonic fibroblasts. METHODS: Mouse embryonic fibroblasts were divided into two groups: Group 1 cells were cultured in DMEM/F12 medium and Group 2 cells were cultured in osteogenic medium. Both groups were then treated with 16, 32, or 100 µM AgNps. Fibroblast proliferation and viability were measured using BrdU and MTT methods at varying time points. Alizarin red staining and alkaline phosphatase (ALP) activity were measured to observe fibroblast differentiation into osteoblasts. Proteomics (cytokine array) was used to detect 111 different cytokines during differentiation. RESULTS: AgNps stimulated proliferation of mouse embryonic fibroblasts at a concentration of 16 µM. Marked enhancement of calcium mineralization was observed in cells cultured with AgNps compared with cells cultured without AgNps. Group 2 cells displayed nodules around the center where the cell density was high. ALP activity of mouse embryonic fibroblasts cultured in osteogenic medium increased during the whole culture period. Addition of AgNps at concentrations of 32 µM and 100 µM induced higher ALP activity at days 7 and 14. Proteomic array results show that low density lipoprotein receptor (LDL-R) and proprotein convertase subtilisin/kexin type 9 (PCSK-9) were significantly increased, while osteoprotegerin (OPG) was significantly reduced in medium containing 16 µM AgNPs. CONCLUSION: AgNps could promote differentiation of mouse embryonic fibroblasts into osteoblastic cells. LDL-R and PCSK-9, as well as OPG, may play a critical role in this process.