Clinical-grade human embryonic stem cell-derived mesenchymal stromal cells ameliorate diabetic retinopathy in db/db mice.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) hold great promise in the treatment of diabetic retinopathy (DR), as evidenced by increasing preclinical and clinical studies. However, the absence of standardized and industrialized clinical-grade donor cells hampers the continued development and large-scale clinical application of MSCs-based therapies for DR. Previously, we have identified a unique population of MSCs generated from a clinical-grade human embryonic stem cell (hESC) line under Good Manufacturing Practice conditions that could be a potential source to address the issues. Here, we investigated the therapeutic potential of the clinical-grade hESC line-derived MSCs (hESC-MSCs) on db/db mice with DR. METHODS: hESC-MSCs were initially characterized by morphological assessment, flow cytometry analysis and trilineage differentiation assays. These cells (5 × 106 cells) were then transplanted intravenously into 12-week-old db/db mice via tail vein, with phosphate-buffered saline transplantation and untreated groups used as controls. The retinal alterations in neural functions and microvascular perfusions, and inflammatory responses in peripheral blood and retina were evaluated at 4 and 6 weeks after transplantation using electroretinography, optical coherence tomography angiography and flow cytometry, respectively. Body weight and fasting blood glucose (FBG) levels were also measured to investigate their systemic implications. RESULTS: Compared with controls, intravenous transplantation of hESC-MSCs could significantly: (i) enhance impaired retinal electroretinography functions (including amplitudes of a-, b-wave and oscillatory potentials) at 4 weeks after transplantation; (ii) alleviate microvascular dysfunctions, especially in the inner retina with significance (including reducing non-perfusion area and increasing vascular area density) at 4 weeks after transplantation; (iii) decrease FBG levels at 4 weeks after transplantation and induce weight loss up to 6 weeks after transplantation and (iv) increase both peripheral blood and retinal interleukin-10 levels at 4 weeks after transplantation and modulate peripheral blood inflammatory cytokines and chemokines levels, such as monocyte chemotactic protein-1, up to 6 weeks after transplantation. CONCLUSIONS: The findings of our study indicated that intravenous transplantation of hESC-MSCs ameliorated retinal neural and microvascular dysfunctions, regulated body weight and FBG and modulated peripheral blood and retinal inflammation responses in a mouse model of DR. These results suggest that hESC-MSCs could be a potentially effective clinical-grade cell source for the treatment of DR.

Extracranial malignant rhabdoid tumors in children: high mortality even with the help of an aggressive clinical approach.

This paper aims to explore the epidemiology, clinical characteristics, and prognosis of extracranial malignant rhabdoid tumors (eMRTs) in children. A systematic review and meta-analysis of studies published in PUBMED, MEDLINE, Web of Science, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) was conducted. The search was limited to studies published between Jan 1, 1990 to Dec 31, 2022, with the last search done on Jan 31, 2023. We identified 496 papers through the literature search, and 12 retrospective cohort studies with 398 patients were included. The pooled age at diagnosis for malignant rhabdoid tumor of the kidney (MRTK) was 10.009 months (95%CI (7.542-12.476)), while extracranial malignant rhabdoid tumor (EERT) was 25.917 months (95%CI (17.304-34.530)). Among the 398 patients with eMRTs, chemotherapy treatment rate (86.8% (95%CI (74.4-96.0%))) was more frequently than radiotherapy treatment (45.4% (95%CI (38.1-52.6%))). The rate of metastasis in all patients was 41.4% (95%CI (33.9-48.9%)), in which the lung metastasis was occupied 70.4% (95%CI (58.0-81.6%)). SMARCB1/INI1 mutation was up to 93.2% (95%CI (81.3-99.8%)). The rate of total surgical resection was 50.4% (95%CI (35.2-65.6%)), while pooled proportion of death in all patients was 68.7% (95%CI (56.9-79.5%)).     Conclusion: EMRTs are highly malignant tumors associated with high mortality rates. The loss of SMARCB1/INI1 gene and the protein expression is observed in the vast majority of eMRTs patients. Patients that suffered MRTK are younger than patients with extrarenal EERT and are more prone to lung metastasis, but there is no significant difference in overall survival, possibly due to the higher rate of R0 resection of primary tumors in MRTK.     Trial registration: The study was registered on PROSPERO with registration number CRD42023400985. What is Known: • Malignant rhabdoid tumor (MRT) is a rare and highly malignant tumor that may originate from embryonic stem cells. The incidence of MRT is exceptionally low, estimated at 0.00006%. • Malignant rhabdoid tumor of the kidney (MRTK) and extrarenal extra-cranial malignant rhabdoid tumor (EERT) tend to manifest between 11 to 18 months of age, with a 5-year survival rate of approximately 17%-36%. What is New: • There is no comprehensive meta-analysis or large-scale case series that reported to systematically introduce the eMRTs clinic outcome and prog-nosis based on largely pooled data. • This study performed a meta-analysis through an extensive literature search and clinical data analysis in order to mainly explore the clinical characteris-tics and prognosis of eMRTs, improving the understanding of eMRTs in children..

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.

The Endoscopic Retrograde Appendicitis Therapy for Acute Appendicitis in Children: A Systematic Review and Meta-Analysis.

Background: Acute appendicitis (AA) is a prevalent abdominal emergency in children, and there has been growing interest in the use of endoscopic retrograde appendicitis treatment (ERAT) over the past two decades. A meta-analysis of published retrospective studies was conducted to investigate the clinical characteristics and therapeutic efficacy of ERAT for AA in children. Methods: A systematic review and meta-analysis of retrospective studies were carried out, encompassing data from PUBMED, MEDLINE, Cochrane, China National Knowledge Infrastructure (CNKI), WanFang, and VIP Database. The search was limited to studies published between January 1, 2012, and June 31, 2022, with the final search conducted on October 31, 2022. No restrictions were imposed regarding publication or study design filters. The registration number in PROSPERO was CRD42022377739. Results: Seven retrospective cohort studies with 423 patients were included. The majority of children who underwent ERAT were male (57.6%, 95% CI 52.8%-62.4%). The ERAT procedure had a high success rate (99.5%, 95% CI 98.2%-100.0%) and averaged around 49 minutes. ERAT's efficacy for treating acute appendicitis was high (99.0%, 95% CI 96.5%-100.0%), with a low recurrence rate (4.2%, 95% CI 2.2%-6.7%). Patients typically stayed in the hospital for about 4.3 days, and the rate of postoperative complications was around 3.9% (95% CI 2.0%-6.2%). Conclusions: Despite the heterogeneity among studies, ERAT appears to be an effective treatment for acute uncomplicated appendicitis in children. It has a high success rate, a low recurrence rate, preserves the appendix's function, and causes minimal damage. ERAT could be considered a safe and effective treatment option for pediatric appendicitis.

Downregulation of miR-144 blocked the proliferation and invasion of nerve cells in Hirschsprung disease by regulating Transcription Factor AP 4 (TFAP4).

BACKGROUND: Hirschsprung's disease (HSCR) is characterized by a dysfunction of enteric neural crest cells (ENCCs) proliferation, migration and premature apoptosis during embryonic development, resulting in aganglionic colon. Our aim is to explore the role of miR-144 with its target gene Transcription Factor AP 4 (TFAP4) in nerve cells in HSCR. METHODS: The relative expression levels of miR-144 in HSCR colon samples were detected by quantitative real-time PCR (RT-qPCR). Western blot assays were conducted to investigate the TFAP4 protein expressing level. The interaction of miR-144 and TFAP4 was predicted with bioinformatics analysis and examined with luciferase reporter assays. Overexpression or knockdown of miR-144 and TFAP4 in 293T and SH-SY5Y cell lines was applied. Cell proliferation, migration and invasion were detected by CCK-8 assays, Transwell migration and invasion assays. Cell cycle and apoptosis was examined by flow cytometric analysis. RESULTS: Downregulation of miR-144 and upregulation of TFAP4 were shown in HSCR. Luciferase reporter assay indicated that miR-144 reduced luciferase activity in 293T and SH-SY5Y transfected with TFAP4-WT-3UTR luciferase reporter and confirmed TFAP4 was the downstream target gene of miR-144. Data showed that miR-144 promoted the cell proliferation, migration and invasion of 293T and SH-SY5Y, while TFAP4 blocked the cell proliferation, migration and invasion. TFAP4 overexpression reversed the miR-144-mediated cell proliferation, migration and invasion of 293T and SH-SY5Y. CONCLUSIONS: Downregulation of miR-144 blocked the cell proliferation and migration of nerve cells via targeting TFAP4 and contributed to the pathogenesis of HSCR. This provides an innovative and candidate target for treatment of HSCR.

Robot-assisted subretinal injection system: development and preliminary verification.

BACKGROUND: To design and develop a surgical robot capable of assisting subretinal injection. METHODS: A remote center of motion (RCM) mechanical design and a master-slave teleoperation were used to develop and manufacture the assisted subretinal surgery robot (RASR). Ten fresh isolated porcine eyes were divided into the Robot Manipulation (RM) group and Manual Manipulation (MM) group (5 eyes for each group), and subretinal injections were performed by the robot and manual manipulation methods, respectively. A preliminary verification of the robot was performed by comparing the advantages and disadvantages of the robot manipulation and manual manipulation by using optical coherent tomography (OCT), fundus photography, and video motion capture analysis after the surgery. RESULTS: Both the robot and the manual manipulation were able to perform subretinal injections with a 100% success rate. The OCT results showed that the average subretinal area was 1.548 mm2 and 1.461 mm2 in the RM and MM groups, respectively (P > 0.05). Meanwhile the volume of subretinal fluid obtained using the retinal map mode built in OCT was not statistically different between the RM and MM groups (P > 0.05). By analyzing the surgical video using Kinovea, a motion capture and analysis software, the results suggest that the mean tremor amplitude of the RM group was 0.3681 pixels (x direction), which was significantly reduced compared to 18.8779 pixels (x direction) in the MM group (P < 0.0001). CONCLUSION: Robot-assisted subretinal injection system (RASR) is able to finish subretinal injection surgery with better stability and less fatigue than manual manipulation.

Gamma-Glutamyl Transferase Combined With Conventional Ultrasound Features in Diagnosing Biliary Atresia: A Two-Center Retrospective Analysis.

OBJECTIVES: To develop and validate a biliary atresia (BA) diagnostic score based on serum gamma-glutamyl transferase (GGT) levels and conventional ultrasound features for discriminating BA in patients with jaundice from two centers. METHODS: A total of 958 patients from one hospital were classified as the derivation cohort, and 725 patients from another hospital were classified as the validation cohort. The optimal GGT cutoff value for diagnosing BA was calculated in the derivation cohort and subsequently verified in the validation cohort. Gallbladder abnormalities and the triangular cord (TC) sign were evaluated in all patients. A BA diagnostic score was developed for diagnosing BA using the GGT levels, gallbladder abnormalities and the TC sign based on the data from the derivation cohort followed by external validation. RESULTS: Based on the optimal cutoff value 350.0 U/L, GGT yielded a sensitivity of 59.3% and specificity of 85.4% in diagnosing BA. The area under the receiver operating characteristic curve (AUC 0.724) was inferior to that of the gallbladder (AUC 0.911, P < .001) and comparable to that of the TC sign (AUC 0.771, P = .128). The combination of GGT and ultrasound diagnosis could help to reduce the misdiagnosis of 9 infants with BA. The BA diagnostic score yielded a sensitivity of 93.3% and specificity of 95.0% with the highest AUC in this study (0.941). CONCLUSIONS: GGT can add diagnostic value to ultrasound examination when diagnosing BA. The BA diagnostic score based on GGT, gallbladder abnormalities and the TC sign shows satisfactory discrimination abilities in BA.

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.

Characteristics of ovarian necrosis in the neonatal ovarian tumor: a single-center retrospective study and review of literature.

To analyze the characteristics of ovarian necrosis in the neonatal ovarian tumor, and review treatments for ovarian torsion in neonates. Neonates with ovarian tumors undergoing surgery in Fujian Maternal and Child Health Hospital (Fujian Children's Hospital) from February 2016 to August 2021 were analyzed retrospectively. Patients were divided into the ovarian necrosis group and control group (without necrosis). Demographic characteristics, prenatal and postnatal examination, operation, and pathological findings were compared and the relevant factors of ovarian necrosis were discussed. 26 neonates were included, 12 in necrosis group and 14 in control group. The maximum diameter of the tumor in necrosis group was smaller than that in control group (P < 0.01). The preoperative CRP in necrosis group was significantly higher than that in control group (P < 0.05). There were no significant differences between two groups in the timeliness of surgery, pathological types, and length of postoperative hospital stay. About 26% of neonatal ovarian torsion could be rescued. Neonatal ovarian necrosis is characterized by a smaller tumor size and a higher preoperative CRP level. Timely surgery after birth might not change the ovarian outcome, but ovarian detorsion could be attempted in neonates to save residual ovarian function.

Super-Resolution Imaging Reveals Dynamic Reticular Cytoophidia.

CTP synthase (CTPS) can form filamentous structures termed cytoophidia in cells in all three domains of life. In order to study the mesoscale structure of cytoophidia, we perform fluorescence recovery after photobleaching (FRAP) and stimulated emission depletion (STED) microscopy in human cells. By using an EGFP dimeric tag as a tool to explore the physical properties of cytoophidia, we find that cytoophidia are dynamic and reticular. The reticular structure of CTPS cytoophidia may provide space for other components, such as IMPDH. In addition, we observe CTPS granules with tentacles.

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.

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.

Autophagy decreases alveolar epithelial cell injury by regulating the release of inflammatory mediators.

To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in the early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar epithelial cells stably expressing GFP-LC3 were treated with an autophagy inhibitor (3-MA) or an autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment for 2, 4, and 6 hr in vitro. In vivo, 20 male Sprague Dawley rats were randomly divided into four groups (model group: No blocking of the hilum in the left lung; control group: Blocking of the hilum in the left lung for 1 hr with dimethyl sulfoxide lavage; 3-MA group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of 3-MA (5 µmol/L) solution lavage; and rapamycin group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of rapamycin (250 nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the nuclear factor kappa B signaling pathway and limited the expression of proinflammatory factors. A contrary result was found after the 3-MA pretreatment. These findings indicate that autophagy reduces ischemia-reperfusion injury by repressing inflammatory signaling pathways in the early stages of hypoxia in vitro and in vivo. Autophagy could be a new protective method for application in lung ischemia-reperfusion injury.

Correction to: CircMYO10 promotes osteosarcoma progression by regulating miR-370-3p/RUVBL1 axis to enhance the transcriptional activity of ß-catenin/LEF1 complex via effects on chromatin remodeling.

Following the publication of the original paper [1], one corresponding author was inadvertently missed.

The effects of ginsenosides on platelet aggregation and vascular intima in the treatment of cardiovascular diseases: From molecular mechanisms to clinical applications.

Thrombosis initiated by abnormal platelet aggregation is a pivotal pathological event that precedes most cases of cardiovascular diseases (CVD). Recently, growing evidence indicates that platelet could be a potential target for CVD prevention. However, as the conventional antithrombotic management strategy, applications of current antiplatelet agents are somewhat limited by their various side effects, such as bleeding risk and drug resistance. Hence, efforts have been made to search for agents as complementary therapies. Ginsenoside, the principal active component extracted from Panax ginseng, has gained much attention for its regulations on multiple crucial events of platelet aggregation. From structural characteristics to clinical applications, this review anatomized the intrinsic structure-function relationship of antiplatelet potency of ginsenosides, and the involved signal pathways were specifically summarized. Additionally, the emphasis was placed on clinical studies that investigate the antithrombotic efficacy of ginsenosides in the treatment of CVD. Further, a broad overview of approaches for improving the bioavailability of ginsenosides was concluded. Limitations and prospects of current studies were also discussed. This study may provide some new insights into the systematic understanding of ginsenosides in CVD treatment and lay a foundation for future research.

Application of WeChat-assisted peri-operative care in children with congenital megacolon.

AIM: This study explored the clinical effects of WeChat-based peri-operative care on parents of children with congenital megacolon. METHODS: Participants were randomly divided into WeChat group and telephone group. This study explored parents' knowledge of the care of children with megacolon, the follow-up rate of children, post-operative defaecation function and complications. RESULTS: WeChat group scored better in nursing knowledge than telephone group, and the difference was statistically significant. The lost follow-up rate in WeChat group was lower than that in telephone group, and the difference was statistically significant. Post-operative defaecation was also better in the WeChat group than in the phone group. Most complications in the phone group were significantly higher than those in the WeChat group. CONCLUSION: Peri-operative care for parents of children with megacolon through WeChat can effectively enhance the level of parental care knowledge, improve defaecation, reduce the occurrence of certain complications and reduce lost follow-up.

CircMYO10 promotes osteosarcoma progression by regulating miR-370-3p/RUVBL1 axis to enhance the transcriptional activity of ß-catenin/LEF1 complex via effects on chromatin remodeling.

BACKGROUND: CircMYO10 is a circular RNA generated by back-splicing of gene MYO10 and is upregulated in osteosarcoma cell lines, but its functional role in osteosarcoma is still unknown. This study aimed to clarify the mechanism of circMYO10 in osteosarcoma. METHODS: CircMYO10 expression in 10 paired osteosarcoma and chondroma tissues was assessed by quantitative reverse transcription polymerase chain reaction (PCR). The function of circMYO10/miR-370-3p/RUVBL1 axis was assessed regarding two key characteristics: proliferation and endothelial-mesenchymal transition (EMT). Bioinformatics analysis, western blotting, real-time PCR, fluorescence in situ hybridization, immunoprecipitation, RNA pull-down assays, luciferase reporter assays, chromatin immunoprecipitation, and rescue experiments were used to evaluate the mechanism. Stably transfected MG63 cells were injected via tail vein or subcutaneously into nude mice to assess the role of circMYO10 in vivo. RESULTS: CircMYO10 was significantly upregulated, while miR-370-3p was downregulated, in osteosarcoma cell lines and human osteosarcoma samples. Silencing circMYO10 inhibited cell proliferation and EMT in vivo and in vitro. Mechanistic investigations revealed that miR-370-3p targets RUVBL1 directly, and inhibits the interaction between RUVBL1 and ß-catenin/LEF1 complex while circMYO10 showed a contrary effect via the inhibition of miR-370-3p. RUVBL1 was found to be complexed with chromatin remodeling and histone-modifying factor TIP60, and lymphoid enhancer factor-1 (LEF1) to promote histone H4K16 acetylation (H4K16Ac) in the vicinity of the promoter region of gene C-myc. Chromatin immunoprecipitation methods showed that miR-370-3p sponge promotes H4K16Ac in the indicated region, which is partially abrogated by RUVBL1 small hairpin RNA (shRNA) while circMYO10 showed a contrary result via the inhibition of miR-370-3p. Either miR-370-3p sponge or ShRUVBL1 attenuated circMYO10-induced phenotypes in osteosarcoma cell lines. MiR-370-3p inhibition abrogated the inhibition of proliferation, EMT of osteosarcoma cells in vitro and in vivo seen upon circMYO10 suppression via Wnt/ß-catenin signaling. CONCLUSIONS: CircMYO10 promotes osteosarcoma progression by regulating miR-370-3p/RUVBL1 axis to promote chromatin remodeling and thus enhances the transcriptional activity of ß-catenin/LEF1 complex, which indicates that circMYO10 may be a potential therapeutic target for osteosarcoma treatment.

Enlarged hepatic hilar lymph node: an additional ultrasonographic feature that may be helpful in the diagnosis of biliary atresia.

OBJECTIVES: To prospectively assess whether the detection of hepatic hilar lymph nodes (LNs) contributes to the diagnosis of biliary atresia (BA). METHODS: A total of 80 jaundiced infants were enrolled in this study and had abdominal ultrasound (US). The hepatic hilar LNs, the gallbladder classification, and the triangular cord (TC) thickness of all infants were evaluated. The area under the receiver operating characteristic curve (AUROC) analysis, t tests, and chi-squared tests were used to compare US signs between infants with BA and those without BA. RESULTS: BA was found in 45 patients and excluded in 35 patients. The length of the hepatic hilar LNs in infants with BA (median with interquartile range, 11 mm (8, 13.5)) was significantly greater than that in infants without BA (0 mm (0, 0)) (p < 0.001). The AUROCs of the enlarged hepatic hilar LNs, gallbladder classification, and TC thickness were 0.867, 0.894, and 0.832, respectively. The accuracy of LNs (87.5%) in the diagnosis of BA was close to that of the gallbladder classification scheme (88.8%) (p = 0.049) and was higher than that of the TC thickness (82.5%) (p = 0.031). The enlarged LNs had the highest sensitivity (93.3%) in distinguishing BA from non-BA. CONCLUSIONS: The presence of enlarged hepatic hilar LNs is an additional highly sensitive sign for the noninvasive diagnosis of BA. Through the combination of enlarged LNs, gallbladder classification, and TC thickness, most BA could be identified. KEY POINTS: • An enlarged hepatic hilar LN is an additional US sign for the noninvasive diagnosis of biliary atresia. • Combining enlarged hepatic hilar LNs, gallbladder classification, and TC thickness, BA could be diagnosed in most infants.

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.