[Impact of cecal ligation and puncture-induced sepsis on the proliferation and differentiation of intestinal stem cells].

OBJECTIVE: To analyze the impact of cecal ligation and puncture (CLP)-induced sepsis on the proliferation and differentiation of intestinal epithelial cells. METHODS: (1) Animal experiment: sixteen male C57BL/6 mice were divided into sham operation group (Sham group) and CLP-induced sepsis model group (CLP group) by random number table method, with 8 mice in each group. After 5 days of operation, the jejunal tissues were taken for determination of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) and intestinal alkaline phosphatase (IAP) by polymerase chain reaction (PCR). The translation of LGR5 was detected by Western blotting. The expression of proliferating cell nuclear antigen (Ki67) was analyzed by immunohistochemistry. IAP level was detected by modified calcium cobalt staining and colorimetry. Immunofluorescence staining was used to detect the expression of Paneth cell marker molecule lysozyme 1 (LYZ1) and goblet cell marker molecule mucin 2 (MUC2). (2) Cell experiment: IEC6 cells in logarithmic growth stage were divided into blank control group and lipopolysaccharide (LPS) group (LPS 5 µg/mL). Twenty-four hours after treatment, PCR and Western blotting were used to analyze the transcription and translation of LGR5. The proliferation of IEC6 cells were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining. The transcription and translation of IAP were detected by PCR and colorimetric method respectively. RESULTS: (1) Animal experiment: the immunohistochemical results showed that the positive rate of Ki67 staining in the jejunal tissue of CLP group was lower than that of Sham group [(41.7±2.5)% vs. (48.7±1.4)%, P = 0.01]. PCR and Western blotting results showed that there were no statistical differences in the mRNA and protein expressions of LGR5 in the jejunal tissue between the CLP group and Sham group (Lgr5 mRNA: 0.7±0.1 vs. 1.0±0.2, P = 0.11; LGR5/ß-actin: 0.83±0.17 vs. 0.68±0.19, P = 0.24). The mRNA (0.4±0.1 vs. 1.0±0.1, P < 0.01) and protein (U/g: 47.3±6.0 vs. 73.1±15.3, P < 0.01) levels of IAP in the jejunal tissue were lower in CLP group. Immunofluorescence saining analysis showed that the expressions of LYZ1 and MUC2 in the CLP group were lower than those in the Sham group. (2) Cell experiment: PCR and Western blotting results showed that there was no significant difference in the expression of LGR5 between the LPS group and the blank control group (Lgr5 mRNA: 0.9±0.1 vs. 1.0±0.2, P = 0.33; LGR5/ß-actin: 0.71±0.18 vs. 0.69±0.04, P = 0.81). The proliferation rate of IEC6 cells in the LPS group was lower than that in the blank control group, but there was no significant difference [positivity rate of EdU: (40.5±3.8)% vs. (46.5±3.6)%, P = 0.11]. The mRNA (0.5±0.1 vs. 1.0±0.2, P < 0.01) and protein (U/g: 15.0±4.0 vs. 41.2±10.4, P < 0.01) of IAP in the LPS group were lower than those in the blank control group. CONCLUSIONS: CLP-induced sepsis inhibits the proliferation and differentiation of intestinal epithelial cells, impairing the self-renewal ability of intestinal epithelium.

Coexistence of kaposiform hemangioendothelioma and capillary malformation: More than a coincidence? Two case reports.

The coexistence of kaposiform hemangioendothelioma (KHE) and capillary malformation (CM) is quite rare, and few relevant studies can be found to confirm whether this phenomenon is accidental. We diagnosed and treated two such patients, revealing interesting phenomena associated with the development of vascular diseases. These cases offer the possibility that the coexistence of KHE and CM is not accidental and open up a new field of research related to pediatric vascular tumors and vascular malformations. Personalization and precision are required in the diagnosis and treatment of such patients, and the present findings provide a reliable theoretical and practical basis for further research on the pathogenesis and therapy of patients with multiple vascular diseases.

High Serum Albumin Levels were Associated with Acute Kidney Injury in Pediatric Surgical Intensive Care Units.

INTRODUCTION: There are limited studies revealing the association between serum albumin concentrations and acute kidney injury (AKI) in critically ill children. METHODS: This was a multicenter retrospective study. Children consecutively admitted to four pediatric surgical intensive care units (PSICUs) between January 2016 and December 2020 were screened for analysis. Patients without recorded albumin values during the PSICU stay were excluded. Data were extracted from the electronic medical records systems of the hospitals. AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. The associations between serum albumin levels and AKI were assessed by using logistic regression models. RESULTS: A total of 7802 children were included in the analysis. The median age of the children was 1.0 (interquartile range (IQR), 0.0-4.0) years. There were 3214 (41.2 %) children who developed AKI. In the univariate logistic regression model, serum albumin levels were associated with AKI (odds ratio (OR) = 1.04, 95 % confidence interval (CI) 1.04-1.05). After adjusting for covariates, serum albumin showed an independent association with AKI (OR = 1.04, 95 % CI 1.03-1.05). Albumin levels above 39.43 g/L (OR = 1.036, 95 % CI 1.002-1.070) were associated with AKI in the unadjusted cubic spline. In the adjusted cubic spline, albumin levels above 40.41 g/L (OR = 1.061, 95 % CI 1.003-1.122) were associated with AKI. CONCLUSION: High serum albumin was associated with AKI in critically ill children in the PSICU. Further studies are needed to validate our findings. TYPE OF STUDY: Prognostic Study. LEVEL OF EVIDENCE: LEVEL II.

Kaposiform Hemangioendothelioma with Bone Destruction: A 16-Year Follow-Up Cohort Study of the Clinical Characteristics and Prognosis.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that often occurs in infants and young children. The goal of this study was to analyze the clinical characteristics of KHE patients with bone destruction and provide clinical guidance for diagnosis and treatment. METHODS: We conducted a descriptive cohort study with follow-up from January 2007 to January 2023 to collect demographic information and tumor-related clinical information from KHE patients with bone destruction. RESULTS: A total of 269 KHE patients were included in the study, of whom 70 (26.0%) patients had tumors with bone destruction. The median age at diagnosis of patients with bone destruction was 19.0 months, which was much later than that of patients without bone destruction (P < 0.001). Patients with bone destruction were more likely to have a decreased range of motion (ROM) (P < 0.001). Metaphysis involvement was more likely to occur in the lower limb bones (P = 0.039), and the lower limb bones were more likely to be associated with decreased ROM (P = 0.001). Tumors involving extracompartmental bone were more likely to have decreased ROM (P = 0.003) and exhibit the Kasabach-Merritt phenomenon (P = 0.006). CONCLUSIONS: Based on the rarity and significant heterogeneity of KHE patients with bone destruction, we should give full play to the role of multidisciplinary teams in addressing disease to reduce the long-term complications of KHE with bone destruction and improve the quality of life of patients. TYPE OF STUDY: Prognostic Study. LEVEL OF EVIDENCE: Level II.

Effects of propranolol on glucose metabolism in hemangioma-derived endothelial cells.

Infantile hemangioma (IH) is the most common benign tumor in children. Propranolol is the first-line treatment for IH, but the underlying mechanism of propranolol treatment in IH is not completely understood. Integrated transcriptional and metabolic analyses were performed to investigate the metabolic changes in hemangioma-derived endothelial cells (HemECs) after propranolol treatment. The findings were then further validated through independent cell experiments using a Seahorse XFp analyzer, Western blotting, immunohistochemistry and mitochondrial functional assays. Thirty-four differentially expressed metabolites, including the glycolysis metabolites glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-bisphosphate, were identified by targeted metabolomics. A KEGG pathway enrichment analysis showed that the disturbances in these metabolites were highly related to glucose metabolism-related pathways, including the pentose phosphate pathway, the Warburg effect, glycolysis and the citric acid cycle. Transcriptional analysis revealed that metabolism-related pathways, including glycine, serine and threonine metabolism, tyrosine metabolism, and glutathione metabolism, were highly enriched. Moreover, integration of the metabolomic and transcriptomic data revealed that glucose metabolism-related pathways, particularly glycolysis, were altered after propranolol treatment. Cell experiments demonstrated that HemECs exhibited higher levels of glycolysis than human umbilical vein ECs (HUVECs) and that propranolol suppressed glycolysis in HemECs. In conclusion, propranolol inhibited glucose metabolism in HemECs by suppressing glucose metabolic pathways, particularly glycolysis.

Laparoscopic Ladd's procedure for intestinal malrotation in small infants with midterm follow-up.

BACKGROUND: The objective of this study was to evaluate the safety and efficacy of laparoscopic Ladd's procedure (LL) for intestinal malrotation (IM) in small infants. METHODS: All patients aged < 6 months with IM who underwent Ladd's procedures between January 2012 and December 2019 were enrolled. The perioperative demographics and midterm follow-up results were retrospectively reviewed and compared between patients who underwent LL and open Ladd's operation (OL). RESULTS: Fifty-five patients were enrolled for analysis. The baseline characteristics were well matched in the two groups. The rate of volvulus was similar in the two groups (76.2% vs. 73.5%, P = 0.81). Two cases in the LL group were converted to OL due to intraoperative bleeding and intestinal swelling. The operative time (ORT) was not significantly different between the two groups (73.8 ± 18.7 vs. 66.8 ± 11.6 min, P = 0.76). Compared to the OL group, the LL group had a shorter time full feed (TFF) (3.1 ± 1.2 vs. 7.3 ± 1.9 days, P = 0.03) and a shorter postoperative hospital stay (PHS) than the OL group (5.5 ± 1.6 vs. 11.3 ± 2.7 days, P = 0.02). The rate of postoperative complications was similar in the two groups (9.5% vs. 11.8%, P = 0.47). The LL group had a lower rate of adhesive obstruction than the OL group, but the difference was not significant (0.0% vs. 11.8%, P = 0.09). One patient suffered recurrence in the LL group, while 0 patients suffered recurrence in the OL group (4.8% vs. 0.0%, P = 0.07). The rate of reoperation in the two groups was similar (4.8% vs. 8.8%). CONCLUSIONS: The LL procedure for IM in small infants was a safe and reliable method that had a satisfactory cosmetic appearance and shorter TFF and PHS than OL.

Toxic effects of sirolimus and everolimus on the development and behavior of zebrafish embryos.

Sirolimus and everolimus have been widely used in children. These mammalian target of rapamycin (mTOR) inhibitors have shown excellent efficacy not only in organ transplant patients as immunosuppressive agents but also in patients with some other diseases. However, whether mTOR inhibitors can affect the growth and development of children is of great concern. In this study, using zebrafish models, we discovered that sirolimus and everolimus could slow the development of zebrafish, affecting indicators such as survival, hatching, deformities, body length, and movement. In addition to these basic indicators, sirolimus and everolimus had certain slowing effects on the growth and development of the nervous system, blood vessels, and the immune system. These effects were dose dependent. When the drug concentration reached or exceeded 0.5 µM, the impacts of sirolimus and everolimus were very significant. More interestingly, the impact was transient. Over time, the various manifestations of experimental embryos gradually approached those of control embryos. We also compared the effects of sirolimus and everolimus on zebrafish, and we revealed that there was no significant difference between these drugs in terms of their effects. In summary, the dose of sirolimus and everolimus in children should be strictly controlled, and the drug concentration should be monitored over time. Otherwise, drug overdosing may have a certain impact on the growth and development of children.

The association between procalcitonin and acute kidney injury in patients stung by wasps.

Introduction: The aim of this study was to investigate the status of serum procalcitonin (PCT) in patients stung by wasps and evaluate the association between PCT levels and acute kidney injury (AKI). Methods: Patients stung by wasps admitted to two tertiary hospitals between January 2017 and December 2020 were screened for enrollment. We evaluated serum PCT levels on admission in patients stung by wasps. The patients were divided into an AKI group and a non-AKI group. A logistic regression model was used to analyze the association between PCT status and AKI. The performance of PCT concentrations in predicting the occurrence of AKI was evaluated by the area under the receiver operating characteristic curve (AUROC). Results: A total of 138 patients were enrolled, and 66 patients suffered AKI. PCT levels were elevated in 78.99% of patients stung by wasps. Nearly half of the patients (47.83%) developed AKI. PCT levels were correlated with creatinine levels on admission (r = 0.787, 95% CI: 0.713-0.844). PCT levels in patients with AKI were higher than those in patients without AKI (p < 0.001). After adjustment for covariates, PCT levels on admission were independently associated with AKI (OR: 1.575, 95% CI: 1.071-2.317, p = 0.021). The AUROC of PCT levels on admission was 0.837 (95% CI, 0.771-0.902, p < 0.001). A PCT level of 0.57 µg/L was the cutoff for maximizing the Youden index; the specificity was 79.45%, and the sensitivity was 73.43%. Conclusion: Serum PCT levels may be a potential biomarker of AKI in patients stung by wasps.

Refractory kaposiform lymphangiomatosis relieved by splenectomy.

Introduction: Kaposiform lymphangiomatosis (KLA) is a rare and complex lymphatic anomaly with a poor prognosis. There is no standard treatment, and drug therapies are the most common therapeutic method. However, some patients' symptoms become gradually aggravated despite medical treatment. Splenectomy may be an alternative option when pharmacological therapies are ineffective. Materials and Methods: We reviewed and evaluated the cases of 3 patients with KLA who ultimately underwent splenectomy. Results: The lesions were diffusely distributed and involved the lungs and spleens of the 3 patients. Laboratory examinations revealed that all three patients had thrombocytopenia and reduced fibrinogen levels. All patients underwent symptomatic splenectomy after the medication failed. Surprisingly, their symptoms greatly improved. Histopathological investigation of the splenic lesions of the three patients confirmed the diagnosis of KLA. Immunohistochemical staining showed positivity for CD31, CD34, podoplanin, Prox-1 and angiopoietin 2 (Ang-2). Discussion: This study aimed to review the features of KLA patients treated by splenectomy and explore the underlying link between splenectomy and prognosis. The reason for the improvement after splenectomy may be related to increased Ang-2 levels and platelet activation in patients with KLA. Future research should seek to develop more targeted drugs based on molecular findings, which may give new hope for the treatment of KLA.

The strategy of laparoscopic surgery for asymptomatic antenatally diagnosed choledochal cyst.

BACKGROUND: The aim was to investigate the characteristics, surgical management, and outcomes of asymptomatic patients with antenatally diagnosed choledochal cysts (ADCCs) and to justify the strategy of laparoscopic surgery (LS) for them in our hospital. METHODS: We developed our LS strategy for asymptomatic ADCCs. Patients with asymptomatic ADCCs who underwent LS or open surgery (OS) during January 2010 and January 2020 were included. Patients with recorded symptomatic ADCCs were exclude. All data of group LS and group OS were statistically compared and analyzed. RESULTS: Twenty-five patients received LS and 18 patients received OS were included. There was no significant difference in baseline characteristics between the groups. A total of 65.1% of biliary sludge formation was detected preoperatively by ultrasonography (US) (72.0% in group LS, 55.6% in group OS, P = 0.26). Compared to the OS group, the LS group had a longer operative time (313.4 ± 27.2 vs. 154.0 ± 11.9 min, P = 0.02), shorter postoperative fasting period (3.1 ± 1.2 vs. 6.2 ± 2.3 days, P = 0.03), and shorter postoperative hospital stay (5.1 ± 1.9 vs. 9.2 ± 1.1 days, P = 0.03). The incidence of late complications, such as reflux cholangitis, adhesive intestinal obstruction, and biliary enteric anastomotic stricture with stone formation, was not significantly different between the two groups. The liver function and liver stiffness of all patients in the two groups were normal. CONCLUSIONS: Based on the strategy for asymptomatic ADCCs in our hospital, the perioperative safety and midterm follow-up results after LS were satisfactory and comparable to those after OS.

Impact of age and tumor size on the development of the Kasabach-Merritt phenomenon in patients with kaposiform hemangioendothelioma: a retrospective cohort study.

Introduction: The Kasabach-Merritt phenomenon (KMP) is a severe complication of kaposiform hemangioendothelioma (KHE). The risk factors for KMP need further investigation. Methods: The medical records of patients with KHE were reviewed. Univariate and multivariate logistic regression models were used for the risk factors for KMP, and the area under the receiver operator characteristic (ROC) curve was used to assess the predictive power of risk factors. Results: A total of 338 patients with KHE were enrolled. The incidence of KMP was 45.9%. Age of onset (P < 0.001, odds ratio [OR] 0.939; 95% confidence interval [CI] 0.914-0.966), lesion size (P < 0.001, OR 1.944; 95% CI 1.646-2.296), mixed type (P = 0.030, OR 2.428; 95% CI 1.092-5.397), deep type (P = 0.010, OR 4.006; 95% CI 1.389-11.556), and mediastinal or retroperitoneal lesion location (P = 0.019, OR 11.864; 95% CI 1.497-94.003) were correlated with KMP occurrence through multivariate logistic regression. ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset (P < 0.001, OR 7.206, 95% CI 4.073-12.749) and a lesion diameter of 5.35 cm (P < 0.001, OR 11.817, 95% CI 7.084-19.714). Bounded by a lesion size of 5.35 cm, we found significant differences in tumor morphology, age of onset, treatments, and hematological parameters. Using an onset age of 4.75 months as a cutoff, we found significant differences in tumor morphology, lesion size, hematological parameters, and prognosis. Conclusion: For KHE patients with an onset age <4.75 months and/or lesion diameter >5.35 cm, clinicians should be wary of the occurrence of KMP. Active management is recommended to improve the prognosis.

Oral antibiotic prophylaxis for infection in patients with vascular anomalies receiving sirolimus treatment: a multicenter retrospective study.

OBJECTIVES: Patients with vascular anomalies (VAs) who receive oral sirolimus may be at high risk of infectious complications. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) has been advocated. However, there have been few evidence-based analyses on this topic. This study assessed the effect of prophylactic TMP-SMZ on the incidence of infections in VA patients receiving sirolimus monotherapy. METHODS: A retrospective, multicenter chart review was performed on all VA patients receiving sirolimus treatment from August, 2013 to January, 2021. RESULTS: Before January 2017, 112 patients were treated with sirolimus without antibiotic prophylaxis. In the subsequent period, 195 patients were treated with TMP-SMZ for at least 12 months during sirolimus therapy. The percentage of patients with at least one serious infection during the initial 12 months of sirolimus treatment did not differ between the groups (difference, 1.1%; 95% CI - 7.0-8.0%). We observed no difference in the incidence of individual infection or total adverse events between the groups. The rate of sirolimus discontinuation due to adverse events did not differ significantly between groups. CONCLUSIONS: We demonstrated that prophylactic TMP-SMZ does not decrease the incidence of infection or improve tolerance in VA patients receiving sirolimus monotherapy.

Case Report: Pancreatic and hepatic kaposiform hemangioendothelioma presenting as consumptive coagulopathy and right hepatic atrophy.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that causes progressive angiogenesis and lymphangiogenesis, which often occurs in the skin or soft tissue, with an acute onset and rapid progression. A 4-year-old girl was admitted to our hospital with a 2-year history of thrombocytopenia, combined with right hepatic atrophy and pancreatic lesion for 3 months. At the age of two, she developed purpura and thrombocytopenia was detected, after treatment with gamma globulin and corticosteroids, the platelet count normalized, but it dropped immediately at lower doses. One year after the cessation of corticosteroids therapy, the patient presented with abdominal pain and abnormal liver function and the magnetic resonance imaging (MRI) revealed right hepatic atrophy and pancreatic occupancy, but the first liver biopsy did not reveal any positive pathological results. By analyzing the clinical manifestations in conjunction with MRI and abnormal coagulation, we considered that the patient might be diagnosed as KHE with Kasabach-Merritt phenomenon, however, sirolimus treatment was ineffective and pancreatic biopsy only showed a tendency for tumors of vascular origin. Finally, we performed a Whipple operation after the right hepatic artery embolization, histological and immunohistochemical examination suggested KHE. Three months postoperatively, the patient's liver function, pancreatic enzymes and blood clotting function gradually returned to normal. KHEs may result in significant blood loss with worsening of the coagulopathy and functional impairment, timely surgical intervention for KHE is necessary when non-invasive or minimally invasive treatment is ineffective, or the symptoms of tumor compression are obvious.

Integrated nontargeted and targeted metabolomics analyses amino acids metabolism in infantile hemangioma.

Infantile hemangioma (IH) is the most common benign tumor in children. However, the exact pathogenesis of IH remains unclear. Integrated nontargeted and targeted metabolic analyses were performed to obtain insight into the possible pathogenic mechanism of IH. The results of nontargeted metabolic analysis showed that 216 and 128 differential metabolites (DMs) were identified between hemangioma-derived endothelial cells (HemECs) and HUVECs in positive-ion and negative-ion models, respectively. In both models, these DMs were predominantly enriched in pathways related to amino acid metabolism, including aminoacyl-tRNA biosynthesis and arginine and proline metabolism. Then, targeted metabolic analysis of amino acids was further performed to further clarify HemEC metabolism. A total of 22 amino acid metabolites were identified, among which only 16 metabolites, including glutamine, arginine and asparagine, were significantly differentially expressed between HemECs and HUVECs. These significant amino acids were significantly enriched in 10 metabolic pathways, including 'alanine, aspartate and glutamate metabolism', 'arginine biosynthesis', 'arginine and proline metabolism', and 'glycine, serine and threonine metabolism'. The results of our study revealed that amino acid metabolism is involved in IH. Key differential amino acid metabolites, including glutamine, asparagine and arginine, may play an important role in regulating HemEC metabolism.

Long-term outcomes of sirolimus treatment for kaposiform hemangioendothelioma: Continuing successes and ongoing challenges.

Treatment with sirolimus, an inhibitor of the mammalian target of rapamycin pathway, has improved the prognosis of patients with kaposiform hemangioendothelioma (KHE). However, the efficacy, durability and tolerability of long-term sirolimus treatment in patients with KHE have not been well elucidated. We performed efficacy and safety assessments based on more than 4.5 years of follow-up in patients receiving sirolimus therapy for KHE. One hundred sixty-seven patients were analyzed, including 102 (61.1%) patients with the Kasabach-Merritt phenomenon (KMP). Follow-up was conducted after a median of 56.0 months. A total of 154 (92.2%) patients had a durable response to sirolimus treatment. No difference in durable response was found between patients without KMP and patients with KMP (95.4% vs 90.2%; difference, 5.2%; 95% confidence interval [CI], -4.0% to 13.1%). Rebound growth occurred in 17.3% of patients upon sirolimus discontinuation. Early treatment discontinuation (odds ratio [OR]: 3.103; 95% CI: 1.529-6.299; P = .002) and mixed lesion type (OR: 2.271; 95% CI: 0.901-5.727; P = .047) were associated with tumor rebound growth. No KHE-related deaths occurred in this cohort. At the last follow-up, approximately 17.4% of patients had active disease and/or changes in body structures to a variable extent. Serious adverse events occurred most commonly during the first year of sirolimus therapy. Follow-up of almost 4.5 years demonstrated that the efficacy of sirolimus persisted over time and that long-term treatment with sirolimus was not associated with unacceptable cumulative toxicities. However, nonresponse, tumor relapse and long-term sequelae remained challenges despite intensified and prolonged sirolimus therapy.

Blockage of glycolysis by targeting PFKFB3 suppresses the development of infantile hemangioma.

BACKGROUND: Infantile hemangioma (IH) is the most common tumor among infants, but the exact pathogenesis of IH is largely unknown. Our previous study revealed that glucose metabolism may play an important role in the pathogenesis of IH and that the inhibition of the glycolytic key enzyme phosphofructokinase-1 suppresses angiogenesis in IH. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a metabolic enzyme that converts fructose-6-bisphosphate to fructose-2,6-bisphosphate (F-2,6-BP), which is the most potent allosteric activator of the rate-limiting enzyme phosphofructokinase-1. This study was performed to explore the role of PFKFB3 in IH. METHODS: Microarray analysis was performed to screen the differentially expressed genes (DEGs) between proliferating and involuting IH tissues. PFKFB3 expression was examined by western blot and immunohistochemistry analyses. Cell migration, apoptosis and tube formation were analyzed. Metabolic analyses were performed to investigate the effect of PFKFB3 inhibition by PFK15. Mouse models were established to examine the effect of PFKFB3 inhibition in vivo. RESULTS: PFKFB3 was identified as one of the most significant DEGs and was more highly expressed in proliferating IH tissues and hemangioma-derived endothelial cells (HemECs) than in involuting IH tissues and human umbilical vein endothelial cells, respectively. PFKFB3 inhibition by PFK15 suppressed HemEC glucose metabolism mainly by affecting glycolytic metabolite metabolism and decreasing the glycolytic flux. Moreover, PFK15 inhibited HemEC angiogenesis and migration and induced apoptosis via activation of the apoptosis pathway. Treatment with the combination of PFK15 with propranolol had a synergistic inhibitory effect on HemECs. Moreover, PFKFB3 knockdown markedly suppressed HemEC angiogenesis. Mechanistically, inhibition of PFKFB3 suppressed the PI3K-Akt signaling pathway and induced apoptotic cell death. More importantly, the suppression of PFKFB3 by PFK15 or shPFKFB3 led to markedly reduced tumor growth in vivo. CONCLUSIONS: Our findings suggest that PFKFB3 inhibition can suppress IH angiogenesis and induce apoptosis. Thus, targeting PFKFB3 may be a novel therapeutic strategy for IH.

Case Report: Bilateral symmetrical primary kaposiform hemangioendothelioma of the femur.

Kaposiform hemangioendothelioma (KHE) is a rare borderline vascular tumor that usually presents as a mass of skin or deep soft tissue. We report a unique case of an 8-year-old KHE patient with bilateral symmetrical sites involving both femurs. The laboratory, radiographic, and pathological findings of the patient were minutely described. During the 6-month follow-up, the symptoms of pain and dysfunction of this patient were relieved. This study aimed to arouse clinicians' concern about the symmetrical sites of KHE patients.

U-shaped association between serum albumin and pediatric intensive care unit mortality in critically ill children.

Introduction: The detailed association between albumin levels and mortality has not been studied in critically ill children. The aim of this study was to reveal an association between albumin levels in detail and mortality in critically ill children. Materials and methods: We retrospectively collected data from children admitted to four pediatric intensive care units (PICUs) in China between January 2015 and October 2020. Restricted cubic spline curves based on logistic regression models were generated to evaluate the detailed associations between serum albumin levels and PICU mortality. Threshold effect analysis was performed using two piecewise regression models. Results: The study included 9,123 children. The overall mortality was 5.3%. The detailed association between serum albumin levels and the risk of mortality followed a U-shape. The risk of mortality decreased with increasing serum albumin levels (OR = 0.919; 95% CI: 0.886, 0.954) in children with serum albumin levels < 43.2 g/L and increased with increasing serum albumin levels (OR = 1.174; 95% CI: 1.044, 1.316) in children with serum albumin levels ≥ 43.2 g/L. Conclusion: There was a U-shaped association between serum albumin levels and mortality in critically ill children in the PICU.

Performance of the PRISM I, PIM2, PELOD-2 and PRISM IV scoring systems in western China: a multicenter prospective study.

BACKGROUND: The aim of this study was to evaluate the performance of the four scoring tools in predicting mortality in pediatric intensive care units (PICUs) in western China. METHODS: This was a multicenter, prospective, cohort study conducted in six PICUs in western China. The performances of the scoring systems were evaluated based on both discrimination and calibration. Discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUC) for each model. Calibration was measured across defined groups based on mortality risk using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 2034 patients were included in this study, of whom 127 (6.2%) died. For the entire cohort, AUCs for Pediatric Risk of Mortality Score (PRISM) I, Pediatric Index of Mortality 2 (PIM2), Pediatric Logistic Organ Dysfunction Score-2 (PELOD-2) and PRISM IV were 0.88 [95% confidence interval (CI) 0.85-0.92], 0.84 (95% CI 0.80-0.88), 0.80 (95% CI 0.75-0.85), and 0.91 (95% CI 0.88-0.94), respectively. The Hosmer-Lemeshow goodness-of-fit Chi-square value was 12.71 (P = 0.12) for PRISM I, 4.70 (P = 0.79) for PIM2, 205.98 (P < 0.001) for PELOD-2, and 7.50 (P = 0.48) for PRISM IV [degree of freedom (df) = 8]. The standardized mortality ratios obtained with the PRISM I, PIM2, PELOD-2, and PRISM IV models were 0.87 (95% CI, 0.75-1.01), 0.97 (95% CI, 0.85-1.12), 1.74 (95% CI, 1.58-1.92), and 1.05 (95% CI, 0.92-1.21), respectively. CONCLUSIONS: PRISM IV performed best and can be used as a prediction tool in PICUs in Western China. However, PRISM IV needs to be further validated in NICUs.