Single centre analysis of factors influencing surgical treatment of splenic trauma in children.

OBJECTIVE: This study aims to investigate determinants impacting the surgical management of splenic trauma in paediatric patients by scrutinizing age distribution, etiological factors and concomitant injuries. The analysis seeks to establish a foundation for delineating optimal operative timing. METHODS: A cohort of 262 paediatric cases presenting with splenic trauma at our institution from January 2011 to December 2021 underwent categorization into either the conservative or operative group. RESULTS: Significantly disparate attributes between the two groups included age, time of presentation, blood pressure, haemoglobin levels, blood transfusion requirements, thermal absorption, American Association for the Surgery of Trauma (AAST) classification and associated injuries. Logistic regression analysis revealed age, haemoglobin levels, AAST classification and blood transfusion as autonomous influencers of surgical intervention (OR = 1.024, 95% CI: 1.011-1.037; OR = 1.067, 95% CI: 1.01-1.127; OR = 0.2760, 95% CI: 0.087-0.875; OR = 7.873, 95% CI: 2.442-25.382; OR = 0.016, 95% CI: 0.002-0.153). The AAST type and age demonstrated areas under the receiver operating characteristic (ROC) curve of 0.782 and 0.618, respectively. CONCLUSION: Age, haemoglobin levels, AAST classification and blood transfusion independently influence the decision for surgical intervention in paediatric patients with splenic trauma. Age and AAST classification emerge as viable parameters for assessing and prognosticating the likelihood of surgical intervention in this patient cohort.

The deacetylation of Foxk2 by Sirt1 reduces chemosensitivity to cisplatin.

In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates cancer cell apoptosis through several post-translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2-induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle-related and apoptosis-related genes in cisplatin-stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1-mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.

Neonatal biliary atresia combined with preduodenal portal vein: A case report.

BACKGROUND: Congenital biliary atresia is a type of obstruction of the bile ducts inside and outside the liver, which can lead to cholestatic liver cirrhosis and eventually liver failure. The preduodenal portal vein (PD-PV) is a rare developmental malformation of the PV. The PV courses in front of the duodenum. However, very few cases of neonatal biliary atresia combined with PD-PV have been reported in the scientific literature. CASE SUMMARY: A 1-mo-and-4-d-old child was admitted to the hospital in January because of yellowish skin. After surgical consultation, surgical intervention was recommended. The child underwent Hilar-jejunal anastomosis, duodenal rhomboid anastomosis, and abdominal drainage under general anesthesia. During the operation, the PV was located at the anterior edge of the duodenum. CONCLUSION: Diagnoses: (1) Congenital biliary atresia; (2) PD-PV; and (3) Congenital cardiovascular malformations. Outcomes: Recommendation for liver transplantation. Lessons: The choice of treatment options for neonatal biliary atresia combined with PD-PV.

A positive feedback loop between Periostin and TGFß1 induces and maintains the stemness of hepatocellular carcinoma cells via AP-2α activation.

BACKGROUND: Liver cancer stem cells (LCSCs) play key roles in the metastasis, recurrence, and chemotherapeutic resistance of hepatocellular carcinoma (HCC). Our previous research showed that the POSTN gene is closely related to the malignant progression and poor prognosis of HCC. This study aimed to elucidate the role of POSTN in generating LCSCs and maintaining their stemness as well as the underlying mechanisms. METHODS: Human HCC tissues and matched adjacent normal tissues were obtained from 110 patients. Immunohistochemistry, western blotting (WB), and RT-PCR were performed to detect the expression of POSTN and stemness factors. The roles of transforming growth factor (TGF)-ß1 and AP-2α in the POSTN-induced stemness transformation of HCC cells were explored in vitro and in vivo using LCSCs obtained by CD133+ cell sorting. RESULTS: The high expression of POSTN was correlated with the expression of various stemness factors, particularly CD133, in our HCC patient cohort and in TCGA and ICGC datasets. Knockdown of POSTN expression decreased the abilities of HCC cell lines to form tumours in xenograft mouse models. Knockdown of POSTN expression also suppressed cell viability and clone formation, invasion, and sphere formation abilities in vitro. Knockdown of AP-2α attenuated the generation of CD133+ LCSCs and their malignant behaviours, indicating that AP-2α was a critical factor that mediated the POSTN-induced stemness transformation and maintenance of HCC cells. The role of AP-2α was verified by using a specific αvß3 antagonist, cilengitide, in vitro and in vivo. Activation of POSTN could release TGFß1 from the extracellular matrix and initiated POSTN/TGFß1 positive feedback signalling. Furthermore, we found that the combined use of cilengitide and lenvatinib suppressed the growth of HCC cells with high POSTN expression more effectively than the use of lenvatinib alone in the patient-derived xenograft (PDX) mouse model. CONCLUSIONS: The POSTN/TGFß1 positive feedback pathway regulates the expression of stemness factors and the malignant progression of HCC cells by regulating the transcriptional activation of AP-2α. This pathway may serve as a new target for targeted gene therapy in HCC.

Construction of a competing endogenous RNA network using differentially expressed lncRNAs, miRNAs and mRNAs in non­small cell lung cancer.

The competing endogenous RNA (ceRNA) network is crucial for the development and progression of tumors, including non­small cell lung cancer (NSCLC). However, what type of ceRNA network regulates NSCLC has not been clarified. The present study aimed to elucidate the long non­coding RNA (lncRNA)/microRNA (miRNA)/mRNA ceRNA network in NSCLC, particularly for the significance of lncRNAs in NSCLC. NSCLC­specific differentially expressed lncRNAs, miRNAs and mRNAs in the Cancer Genome Atlas (TCGA) were analyzed and their relationship was analyzed by a ceRNA network. Their potential functions of differentially expressed mRNAs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, the expression levels of four selected lncRNAs in TCGA were determined and their associated survival of patients was examined. In addition, the expression profiles of these four lncRNAs in 48 NSCLC specimens and cell lines, their cellular distribution and associated clinical parameters were examined. We successfully constructed a ceRNA network, including 113 lncRNAs, 12 miRNAs and 36 mRNAs differentially expressed between NSCLC and non­tumor tissues. LINC00525, MED4­AS1, STEAP2­AS1 and SYNPR­AS1 lncRNAs were selected and validated for their association with the survival of NSCLC patients. The expression of these lncRNAs was upregulated in 48 NSCLC tissues and was varying in NSCLC cells. While LINC00525 was mainly expressed in the cytoplasm, MED4­AS1 was in both the nucleus and cytoplasm of A549 cells. In addition, the expression of LINC00525 was significantly associated with smoking history (P<0.05); MED4­AS1 was significantly associated with women, poor differentiation and lymph node metastasis (P<0.05); STEAP2­AS1 was significantly associated with women (P<0.01); and SYNPR­AS1 was significantly associated with women and adenocarcinoma (P<0.05). These lncRNAs may be valuable biomarkers for prognosis of NSCLC and the ceRNA network may provide new insights in the pathogenesis of NSCLC.

Gene expression profiling reveals upregulated FUT1 and MYBPC1 in children with pancreaticobiliary maljunction.

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735-1.000) and 0.960 (95%CI=0.891-1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.

Organoids of liver diseases: From bench to bedside.

Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present, research on liver diseases is conducted mainly through cell culture, animal models, pathological specimens, etc. However, these methods cannot fully reveal the pathogenic mechanism and therapeutic characteristics of individualized liver diseases. Recent advances in three-dimensional cell culture technology (organoid culture techniques) include pluripotent stem cells and adult stem cells that are cultured in vitro to form self-organizing properties, making it possible to achieve individualized liver disease research. This review provides a comprehensive overview of the development of liver organoids, the existing and potential applications of liver regenerative medicine, the pathogenesis of liver disease heterogeneity, and drug screening.

Risk factors of atrial fibrillation occurring after radical surgery of esophageal carcinoma.

BACKGROUND: Atrial fibrillation (AF) is a common complication after radical surgery of esophageal cancer. The aim of this study was to explore AF risk factors after radical surgery of esophageal carcinoma. METHOD: The data of 335 patients with esophageal cancer who were admitted in our hospital from January 2014 to August 2016 for the first time were retrospectively analyzed. We retrieved the papers in some data banks using the search terms including English and Chinese search terms, and obtained 13 factors which were mentioned in more than 6 papers. The 13 factors including age, gender, history of smoking, history of hypertension, history of peripheral vascular disease, history of cardiac stents or angina pectoris, preoperative pulmonary infection, preoperative brain natriuretic peptide (BNP) level, preoperative left ventricular diastolic dysfunction, operative method, lesion location, intraoperative blood transfusion, adhesion between lymph nodes and pericardium, underwent univariate and multivariate analyses. RESULTS: Of the 335 patients with esophageal cancer, 48 had AF within one week after operation. Univariate analysis indicated that the age (OR: 4.89; CI: 2.53-9.47, P: 0.000), gender (OR: 2.26; CI: 1.17-4.37, P: 0.013), history of peripheral vascular disease (OR: 2.29; CI: 1.06-4.92, P: 0.030), history of cardiac stents or angina pectoris (OR: 27.30; CI: 12.44-59.91, P: 0.000), preoperative BNP level (OR: 27.13; CI: 10.97-67.06, P: 0.000), preoperative left ventricular diastolic dysfunction (OR: 2.22; CI: 1.19-4.14, P: 0.012), operative method (OR: 2.09; CI: 1.002-4.380, P: 0.046), intraoperative blood transfusion (OR: 20.24; CI: 8.39-48.82, P: 0.000), and adhesion between lymph nodes and pericardium were risk factors (OR: 2.05; CI: 1.08-3.87, P: 0.024). Furthermore, multivariate analysis displayed that advanced age (OR: 5.044; CI: 1.748-14.554, P: 0.003), male (OR: 6.161; CI: 2.143-17.715, P: 0.001), history of cardiac stents or angina pectoris (OR: 48.813; CI: 13.674-174.246, P: 0.000), preoperative BNP > 100 (OR: 41.515; CI: 9.380-183.732, P: 0.000), open surgery (OR: 3.357; CI: 1.026-10.983, P: 0.045), intraoperative blood transfusion (OR: 58.404; CI: 10.777-316.509, P: 0.000), and adhesion between lymph nodes and pericardium (OR: 3.954; CI: 1.364-11.459, P: 0.011) were risk factors which could increase the incidence of postoperative AF. CONCLUSION: We should pay attention to the above risk factors in order to reduce the incidence of postoperative AF.

Gene expression profiling reveals upregulated FUT1 and MYBPC1 in children with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.

Factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation: a retrospective case study in Southeast China.

OBJECTIVE: The aim of this study was to evaluate factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation (CCM). DESIGN: A 3-year retrospective study was undertaken between January 2013 and December 2015 in four centres in China. SETTING: This involved a retrospective chart review of paediatric patients with CCM in four large hospitals in Southeast China. PARTICIPANTS: Sixty-five paediatric patients with CCM were included in this study. We derived all available information on patient demographics, clinical characteristics, preoperative complications and surgical methods from the charts of all these patients. INTERVENTIONS: Univariate and multivariate logistic regression analyses were used to evaluate factors significantly affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM. RESULTS: Twenty-three of the 65 case surgeries were performed using laparoscopic technique, and 42 surgeries were performed by conventional open surgery. The median operating time was 215 min (range 120-430 min). The morphological subtype of CCM and the presence of cholecystitis or cholangitis were the only factors found to affect the operating time (p<0.05). Logistic regression analysis confirmed cholangitis as an independent risk factor. CONCLUSIONS: The morphological subtype of CMM and the presence of cholecystitis or cholangitis are factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM, whereas cholangitis is an independent risk factor.

MicroRNA-7 enhances cytotoxicity induced by gefitinib in non-small cell lung cancer via inhibiting the EGFR and IGF1R signalling pathways.

Gefitinib is a tyrosine kinase inhibitor that has been used for the treatment of non-small-cell lung carcinoma (NSCLC). The ability of miR-7 to enhance gefitinib-induced cytotoxicity in NSCLC cells was evaluated in this study. We found that miR-7 significantly decreased the IC50 of gefitinib and inhibited cell growth. G0/G1 cell cycle arrest and cell apoptosis were increased after the treatment of gefitinib coupled with miR-7 transfection. In addition, levels of Raf1, IGF1R, and PI3K and phosphorylation levels of Akt and ERK were also significantly decreased. Our results suggest that miR-7 may provide a novel therapeutic target for the treatment of NSCLCs.

Zinc finger protein ZBTB20 promotes cell proliferation in non-small cell lung cancer through repression of FoxO1.

In the present study, we found that ZBTB20, a member of the POK (POZ and Krüppel) family of transcriptional repressors, was significantly up-regulated in lung cancer tissues, compared with adjacent normal tissues. Our in vitro studies further found that ZBTB20 overexpression promoted, while its inhibition using small interfering RNA suppressed cell proliferation. Consistently, key regulators in cell-cycle progression, such as Cyclin D1, Cyclin E, P21 and P27, were also regulated by ZBTB20. At the molecular level, we further revealed that FoxO1, a tumor suppressor in multiple human cancers, was transcriptionally repressed by ZBTB20. Therefore, our results highlight an important role for ZBTB20 in controlling NSCLC development, which might be helpful to identify potential therapeutic targets for its treatment.

Overcoming 5-Fu resistance in human non-small cell lung cancer cells by the combination of 5-Fu and cisplatin through the inhibition of glucose metabolism.

5-Fu is a pyrimidine analog which is wildly used in the treatment of cancers. The development of strategies that increase its anticancer activity has been studied over the past 20 years. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. In this study, we investigate the glucose metabolic profiles of non-small cell lung cancer cells in response to 5-Fu and cisplatin. Interestingly, the glucose metabolism of A549 cells is activated by 5-Fu treatment but suppressed by cisplatin treatment. We generalize 5-Fu-resistant and cisplatin-resistant cell lines from A549 cells. The glucose metabolism in 5-Fu-resistant cells is increased but decreased in cisplatin-resistant cells. In addition, glycolysis inhibition sensitizes lung cancer cells to 5-Fu. Importantly, we report a synergistic inhibitory effect on lung cancer cells by the combination of 5-Fu with cisplatin through the suppression of glucose metabolism both in vitro and in vivo. Moreover, restoration of glucose metabolism by overexpression of glycolytic key enzymes renders A549 cells resistant to 5-Fu. In summary, our study indicates that glycolysis inhibition contributes to the synergistic antitumor effect of combinational therapy, and targeting glycolysis could be an effective strategy for overcoming 5-Fu resistance in cancer therapy.

[Clinical application and animal experiment of thoracic tracheal reconstruction by using pulmonary tissue flap].

OBJECTIVE: To study the usability of pulmonary tissue flap in the reconstruction of the thoracic trachea. METHODS: Over half perimeter anterior and posterior wall and 6 to 8 tracheal cartilagious rings of dog trachea were resected. The nickel-titanium alloy mesh stent was placed inside the lumen for repair of the defect of the tracheal wall by nearby pulmonary tissue flap with the vascularized segment. The dogs were killed from 2 months to 12 months after operation. Specimens were taken and observed under light and electron microscope. Clinically, 4 patients were treated by this way operation [right common tracheal scarred stenosis and atresia (1), mixed cancerization in the lower part of the common trachea (1) and left common tracheal carcinoid (2)]. RESULTS: No stenosis and granulation tissue were observed in the prosthetic lumen, in which there was comparative continuous stratified ciliated columnar epithelium. All patients recovered respiratory function. CONCLUSION: Pulmonary tissue flap is a promising prosthesis of thoracic tracheal reconstruction.