Objective:To investigate the clinical characteristics of omphalocele, and to assess the risk factors associated with adverse outcomes.Methods:A retrospective cohort study was conducted. Clinical data of 224 patients diagnosed with omphalocele, who were hospitalized at Children′s Hospital, Zhejiang University School of Medicine from January 2013 to December 2022, were collected. Based on their discharge outcomes, the patients were classified into 2 groups: favorable outcomes and unfavorable outcomes. Chi-square test or continuity correction χ2 test or Fisher exact probability method, and Mann-Whitney U test were used for intergroup comparisons. Logistic regression analysis was performed to identify risk factors associated with adverse outcomes in omphalocele. Results:Among the 224 patients with omphalocele, 126 were male. A total of 208 patients (92.9%) had favorable outcomes, while 16 patients (7.1%) had unfavorable outcomes. In the unfavorable outcomes group, 14 patients had giant omphaloceles, while 100 patients had giant omphaloceles in the favorable outcomes group. The rates of herniation of more than two intra-abdominal organs in the hernial sac, congenital heart defects, patent ductus arteriosus, pulmonary hypertension, sepsis and infection of the hernial sac, were all higher in the unfavorable outcomes group compared to the favorable outcomes group (all P<0.05). Patients with unfavorable outcomes had longer mechanical ventilation time, duration of oxygen use, duration of parenteral nutrition, hospital stays, and higher rates of parenteral nutrition-associated cholestasis compared to those with favorable outcomes (all P<0.01). Multivariate Logistic regression analysis indicated that pulmonary hypertension ( OR=9.39, 95% CI 1.20-73.32), sepsis ( OR=8.59, 95% CI 1.32-55.86), and congenital heart defects ( OR=6.55, 95% CI 1.11-38.73) were all independent risk factors for adverse outcomes in omphalocele (all P<0.05). Conclusions:Infants with omphalocele are prone to complications such as cardiovascular malformations, infections, and pulmonary hypertension. Adverse outcomes in omphalocele are associated with pulmonary hypertension, sepsis, and congenital heart defects.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objective To explore the potential relationship between ubiquitination of transforming growth factor kinase 1(TAK1)/nuclear factor-κB(NF-κB)signaling pathway mediated by ring finger protein 99(RNF99)and septic acute respiratory distress syndrome(ARDS).Methods Plasmid and siRNA transfection were conducted to overexpress or knock down RNF99 in MLE12,and expressions of p65 phosphate and p65 protein were analyzed.The protein interaction between RNF99 and TRAF6 or TAK1 was analyzed by immunoprecipitation assay.Forty mice were randomly divided into WT plus PBS,WT plus LPS,RNF99 specific expression(TG)plus PBS,and TG plus LPS groups,with 10 mice in each group.Sepsis was induced by intraperitoneal injection of 30 mg/kg LPS.Results As compared with vector group,protein expression levels of TRAF6 and TAK1 in MLE12 cells decreased significantly in RNF99 group(P<0.05).Ubiquitinated TRAF6 protein increased in MLE12 cells with RNF99 knockdown.As compared with LPS plus vector group,phosphorylation level of p65 in MLE12 cells was signifi-cantly lower in LPS plus RNF99 group(P<0.05).As compared with si-NC group,protein expression levels of RNF99 and IκBα in si-RNF99 group decreased significantly(P<0.05).As compared with LPS plus si-NC group,phosphorylation level of p65 in LPS plus si-RNF99 group increased significantly(P<0.05).The staining percentage of CD68 macrophages in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Phosphorylation level of p65 in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Conclusion RNF99 regulates NF-κB signaling pathway by interacting with the key regulator of NF-κB signaling pathway(TRAF6/TAK1),and improves lung injury after intraperitoneal injection of LPS in mice.

Medical quality and safety are the foundation for the high-quality development of public hospitals.The concept of Multi-disciplinary Treatment(MDT)is of great value for functional departments of hospitals to collaborate in carrying out medi-cal quality management practices.Children's Hospital,Zhejiang University School of Medicine explored a new quality manage-ment model,constructed the MDT practice path for medical quality in administration,and formed a closed-loop management process where clinical departments actively initiate consultations,various administrative functional departments collaborate and in-teract in a two-way manner,accurately identify and solve clinical problems,and continuously track and feedback outcomes.After the inception of this path,the overall level of medical quality and safety in the hospital has been comprehensively improved,mainly manifested in the enhancement of quality control capabilities of clinical departments,optimization of core performance e-valuation indicators,and remarkable improvement in patient satisfaction,thereby holding profound significance for high-quality development of the hospital.

Objective:To investigate the stability and feasibility of using absorbable screws during Bernese periacetabular osteotomy.Methods:A retrospective analysis was conducted on a 36 year-old woman diagnosed with developmental dysplasia of the hip, who had undergone Bernese periacetabular osteotomy. Finite element analysis was used to simulate the stability of the acetabulum under loads of 10%, 20%, 50%, and 100% of the patient's weight. The structural stiffness of the pelvis and the maximum equivalent stress on the absorbable screws were observed under different conditions, including whether the acetabular bone block and the ilium were in contact, whether 3 or 4 screws were used, and whether a graft (including fibular cortical bone and PEEK grafts) was used.Results:The structural stiffness of the pelvis fixed with four screws increased by 67%-94% compared to that with three screws. After using a graft, the structural stiffness of the pelvis increased by 50%-83%. As the load increased, the maximum equivalent stress on the screws also increased. When the acetabular bone block and the ilium had no contact, no graft was used, and only three screws were used for fixation, the maximum equivalent stress could reach 518.9 MPa, while this value dropped to 61% when four screws were used (318.7 MPa). When the acetabular bone block and the ilium were in contact, the maximum equivalent stress was about 12% of that when there was no contact, regardless of the number of screws used. When a cortical bone graft or a PEEK graft was used, the maximum equivalent stress could drop to 21%-26% of that without a graft. When the screw strength was 130 MPa, a load of 20% of body weight was applied, and only three screws were used without a graft, the equivalent stress could exceed the strength of the screw; if four screws were used, the equivalent stress was slightly higher than the strength of the screw when a load of 50% of body weight was applied. However, when a graft was used (either cortical bone or PEEK), even when a load of 100% of body weight was applied, the equivalent stress was slightly lower than the strength of the screw.Conclusion:Absorbable screws can provide sufficient stability for Bernese periacetabular osteotomy. The contact between the acetabular bone block and the ilium, an increase in the number of screws, and the use of grafts (cortical bone and PEEK grafts) can further improve stability. Therefore, absorbable screws have broad application prospects in Bernese periacetabular osteotomy.

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg^-1） groups， and a trimetazidine group （0.002 g·kg^-1）. By intragastric administration of vitamin D₃ and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

This article introduces a recent paper published in JAMA titled " Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomised clinical trial". The paper details the design, results, and implications of a randomized controlled clinical study of the efficacy and safety of tirzepatide in overweight/obese adults in China(SURMOUNT-CN). This study represents the first Chinese evidence supporting tirzepatide for the treatment of obesity, offering a potent therapeutic option for the prevention and treatment of obesity and weight-related comorbidity.

Administrative multi-disciplinary team (MDT) is an efficient management approach that involves multiple administrative departments working together to solve cross functional systemic problems. Grid management improves management efficiency by constructing a three-level management network, efficiently transmitting information and coordinating resources. Starting from 2021, Children′s Hospital, Zhejiang University School of Medicine has adopted a combination of administrative MDT and grid management, with the average length of stay as the starting point to carry out medical efficiency management. Through the three stages of pre-, during-, and post-treatment, the hospital has reconstructed processes from technological innovation, information construction, team collaboration, and other aspects to shorten ineffective length of stay. After 3 years of practice, the average length of stay has been reduced from 6.41 d to 5.54 d, achieving an improvement in service efficiency while ensuring medical quality and safety.

Objective:To investigate the metabolomic characteristics of amniotic fluid in pregnant women with fetal growth restriction (FGR) by targeted metabolomics, identify differential metabolites with biomarker potential, analyze metabolic pathways, and provide metabolic clues for the study of FGR pathogenesis.Methods:From June 2020 to November 2023, amniotic fluid samples were prospectively collected from 19 FGR fetuses (FGR group) and 30 normal-weight fetuses (control group) at the Affiliated Guangdong Second Provincial General Hospital of Jinan University. Targeted metabolomic analysis of amniotic fluid samples (taken at 16-32 gestational weeks) was performed using liquid chromatography- tandem mass spectrometry. Cluster analysis and multivariate statistical analysis were used to analyze the differences in metabolic profiles between the FGR and control groups. Metabolic pathway enrichment analysis was conducted using metabolomics databases, and potential biomarkers were identified using receiver operating characteristic (ROC) curve analysis.Results:A total of 16 differential metabolites were identified between the FGR and control groups, including gallic acid, 6-hydroxy-nicotinic-acid, 2-methyl-valeric-acid, undecanoic acid, trimethylamine, γ-linolenic acid, decanoylcarnitine, α-linolenic acid, 4-ethyl-caprylic-acid, oleic acid, O-hexyl carnitine, L-theanine,turanose, 4-hydrocinnamic acid, L-aspartic acid, and 3-methyl-valeric-acid. These metabolites were involved in metabolic pathways such as unsaturated fatty acid biosynthesis, niacin and nicotinamide metabolism, carbon metabolism, and fatty acid biosynthesis. ROC curve analysis of the 16 differential metabolites revealed that nine had an area under the ROC curve (AUC)>0.7, including oleic acid (AUC= 0.851, 95% CI: 0.737-0.965), α-linolenic acid (AUC=0.798, 95% CI: 0.664-0.933), 4-hydrocinnamic acid (AUC=0.756, 95% CI: 0.619-0.895), L-aspartic acid (AUC=0.747, 95% CI: 0.595-0.900), 4-ethyl-caprylic- acid (AUC=0.746, 95% CI: 0.610-0.881), O-hexyl carnitine (AUC=0.746, 95% CI: 0.610-0.881), decanoylcarnitine (AUC=0.735, 95% CI: 0.589-0.881), turanose (AUC=0.735, 95% CI: 0.589-0.882), and 2-methyl-valeric-acid (AUC=0.725, 95% CI: 0.577-0.872), indicating their potential as biomarkers. Conclusions:FGR fetuses exhibit significant differences in metabolites, involving fatty acids and amino acids related to hypoxic stress and inflammatory responses. Oleic acid and other metabolites can serve as potential biomarkers related to the growth and development of FGR fetuses.

Objective:To investigate the role and mechanism of N 6-methyladenosine (m 6A) methyltransferase-like 3 (METTL3) in vascular calcification (VC) of chronic kidney disease (CKD) through apoptosis-associated protein. Methods:(1) Real-time fluorescence quantitative PCR was used to test METTL3 mRNA in serum of maintenance hemodialysis (MHD) patients. (2) Western blotting was used to detect the expression of METTL3 protein in high-phosphorus stimulated vascular smooth muscle cells (VSMCs), and immunofluorescence double lable was used to observe the distribution of METTL3 and Runt-related transcription factor 2 (Runx2). The METTL3 overexpressed and knockdown plasmids were constructed and transfected into VSMCs. Alizarin red staining was used to detect calcification degree. Western blotting was used to detect the expressions of osteogenic markers [Runx2, bone morphogenetic protein-2(BMP-2), collagen Ⅰ] and apoptosis- related proteins Bax and Bcl-2. (3) SD rats were randomly divided into control group, CKD-VC group and S-adenosylhomocysteine (SAH) intervention group. The calcification of thoracic aorta was evaluated by von Kossa staining, and the protein expressions of Runx2, Bax and Bcl-2 were detected by immunohistochemistry and Western blotting.Results:(1) METTL3 mRNA expression in MHD patients with VC was significantly lower than that in non-VC patients ( P<0.05), and was negatively correlated with coronary artery calcium score ( r=-0.65, P<0.001). (2) The expression of METTL3 in VSMCs stimulated by high phosphorus was decreased and showed a time dependence. Immunofluorescence double label showed that METTL3 and Runx2 were co-expressed in the nucleus. METTL3 was overexpressed in high-phosphorus induced VSMCs, and the expressions of Runx2, collagen I and BMP-2 were significantly decreased, accompanied by the decrease of calcified nodules and Bax/Bcl-2 ratio (all P<0.05). Conversely, METTL3 knockdown aggravated VSMCs calcification by inducing apoptosis. (3) Furthermore, METTL3 inhibitor SAH was administered in vivo, and it was found that inhibition of METTL3 expression significantly increased the calcification of rat thoracic aorta, and the Bax/Bcl-2 ratio and Runx2 expression were up-regulated. Conclusions:Serum METTL3 level is reduced in MHD patients with VC. In vivo and in vitro studies demonstrate that METTL3 inhibits VC in CKD by mediating the apoptosis-related protein Bax/Bcl-2.