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1.
Mol Carcinog ; 63(4): 677-687, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38362848

ABSTRACT

N6 -methyladenosine (m6 A) is the most prevalent epigenetic modification on eukaryotic messenger RNAs. Recent studies have focused on elucidating the key role of m6 A modification patterns in tumor progression. However, the relationship between m6 A and transcriptional regulation remains elusive. Nanopore technology enables the quantification of m6 A levels at each genomic site. In this study, a pair of tumor tissues and adjacent normal tissues from clear cell renal cell carcinoma (ccRCC) surgical samples were collected for Nanopore direct RNA sequencing. We identified 9644 genes displaying anomalous m6 A modifications, with 5343 genes upregulated and 4301 genes downregulated. Among these, 5224 genes were regarded as dysregulated genes, encompassing abnormal regulation of both m6 A modification and RNA expression. Gene Set Enrichment Analysis revealed an enrichment of these genes in pathways related to renal system progress and fatty acid metabolic progress. Furthermore, the χ2 test demonstrated a significant association between the levels of m6 A in dysregulated genes and their transcriptional expression levels. Additionally, we identified four obesity-associated genes (FTO, LEPR, ADIPOR2, and NPY5R) among the dysregulated genes. Further analyses using public databases revealed that these four genes were all related to the prognosis and diagnosis of ccRCC. This study introduced the novel approach of employing conjoint analysis of m6 A modification and RNA expression based on Nanopore sequencing to explore potential disease-related genes. Our work demonstrates the feasibility of the application of Nanopore sequencing technology in RNA epigenetic regulation research and identifies new potential therapeutic targets for ccRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Nanopore Sequencing , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Transcriptome , Epigenome , Epigenesis, Genetic , RNA , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics
2.
Int Immunopharmacol ; 122: 110555, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37399607

ABSTRACT

Liver fibrosis can progress to cirrhosis and hepatocellular carcinoma, which may eventually lead to liver failure and even death. No direct anti-fibrosis drugs are available at present. Axitinib is a new generation of potent multitarget tyrosine kinase receptor inhibitors, but its role in liver fibrosis remains unclear. In this study, a CCl4-induced hepatic fibrosis mouse model and a TGF-ß1-induced hepatic stellate cell model were used to explore the effect and mechanism of axitinib on hepatic fibrosis. Results confirmed that axitinib could alleviate the pathological damage of liver tissue induced by CCl4 and inhibit the production of glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. It also inhibited collagen and hydroxyproline deposition and the protein expression of Col-1 and α-SMA in CCl4-induced liver fibrosis. In addition, axitinib inhibited the expression of CTGF and α-SMA in TGF-ß1-induced hepatic stellate cells. Further studies showed that axitinib inhibited mitochondrial damage and reduced oxidative stress and NLRP3 maturation. The use of rotenone and antimycin A confirmed that axitinib could restore the activity of mitochondrial complexes I and III, thereby inhibiting the maturation of NLRP3. In summary, axitinib inhibits the activation of HSCs by enhancing the activity of mitochondrial complexes I and III, thereby alleviating the progression of liver fibrosis. This study reveals the strong potential of axitinib in the treatment of liver fibrosis.


Subject(s)
NLR Family, Pyrin Domain-Containing 3 Protein , Transforming Growth Factor beta1 , Mice , Animals , Transforming Growth Factor beta1/metabolism , Axitinib/therapeutic use , Axitinib/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Liver/pathology , Hepatic Stellate Cells , Mitochondria/metabolism , Carbon Tetrachloride/adverse effects
3.
Front Pediatr ; 11: 1131629, 2023.
Article in English | MEDLINE | ID: mdl-37114006

ABSTRACT

Background: Donor shortage is an important limitation of liver transplantation (LT). Split liver transplantation (SLT) may increase the sources of donors and reduce the problem of organ shortage. However, there are no standard criteria of the selection of SLT donor, especially regarding the donor age. Methods: We retrospectively analyzed the clinical data of children who received initial SLT between January 2015 and December 2021. Based on the age of donors, the patients were divided into groups A (1-10 years old; n = 26), B (10-45 years old; n = 87), and C (45-55 years old; n = 27). The short-term (<1 year after SLT) outcomes of the recipients were analyzed. Results: A total of 140 patients received SLT from 122 donors. The 1-, 3- and 12-month patient survival rates in group A were 100.0%, and the graft survival rates were 92.3%. The 1-, 3- and 12-month survival rates of patient and graft in group B were 97.7%, 96.6%, and 95.0%, respectively, and in group C were 85.2%, 85.2%, and 81.1%, respectively. The patient survival rate was significantly lower in group C than in groups A and B (p = 0.0082). There was no significant difference in graft survival between the three groups (p = 0.0545). Conclusions: Similar results were obtained for pediatric SLT with donors <10 years old and 10-45 years old. Pediatric SLT can be performed with older donors (45-55 years) after strict donor selection and selection of appropriate recipients.

4.
Brain Behav ; 13(3): e2921, 2023 03.
Article in English | MEDLINE | ID: mdl-36795044

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is one of the most common systemic neurodegenerative diseases and is related to the loss of dopaminergic neurons in the substantia nigra. Several studies verified that microRNA (miRNAs) targeting the Bim/Bax/caspase-3 signaling axis is involved in the apoptosis of dopaminergic neurons in substantia nigra. In this study, we aimed to explore the role of miR-221 in PD. METHODS: To examine the function of miR-221 in vivo, we used a well-established 6-OHDA-induced PD mouse model. Then we conducted adenovirus-mediated miR-221 overexpression in the PD mice. RESULTS: Our results showed that miR-221 overexpression improved motor behavior of the PD mice. We demonstrated that overexpression of miR-221 reduced the loss of dopaminergic neurons in the substantia nigra striatum by promoting their antioxidative and antiapoptosis capacities. Mechanistically, miR-221 targets Bim, thus inhibiting Bim and Bax caspase-3 mediated apoptosis signaling pathways. CONCLUSION: Our findings suggest miR-221 participates in the pathological process of PD and might be a potential drug target and provide new insight into PD treatment.


Subject(s)
MicroRNAs , Parkinson Disease , Mice , Animals , Parkinson Disease/metabolism , Dopaminergic Neurons/metabolism , Caspase 3/metabolism , bcl-2-Associated X Protein/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Apoptosis , Substantia Nigra/metabolism , Mice, Inbred C57BL , Disease Models, Animal
5.
Phytomedicine ; 112: 154687, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36804756

ABSTRACT

BACKGROUND: Hepatocellular carcinoma has high ability of vascular invasion and metastasis. Vasculogenic mimicry (VM) is closely related to the metastasis and recurrence of hepatocellular carcinoma (HCC). According to previous research, Chloranthus henryi has anti-tumor effect, but its molecular mechanism in the treatment of HCC has not yet been stated. PURPOSE: In our study, we aimed to investigate the effect of the extract of Chloranthus henryi in HCC and its target and molecular mechanism. We hoped to explore potential drugs for HCC treatment. STUDY DESIGN/METHODS: In this study, we isolated a chalcone compound from Chloranthus henryi, compound 4, identified as flavokawain A (FKA). We determined the anti-HCC effect of FKA by MTT and identified the target of FKA by molecular docking and CETSA. Hepatoma cells proliferation, migration, invasion, and VM formation were examined using EDU, wound healing, transwell, vasculogenic mimicry, and IF. WB, RT-PCR, and cell transfection were used to explore the mechanism of FKA on hepatoma cells. Tissue section staining is mainly used to demonstrate the effect of FKA on HCC in vivo. RESULTS: We confirmed that FKA can directly interact with CXCL12 and HCC proliferation, migration, invasion, and VM formation were all inhibited through reversing the EMT progress in vitro and in vivo through the PI3K/Akt/NF-κB signaling pathway. Additionally, by overexpressing and knocking down CXCL12, we got the same results. CONCLUSION: FKA attenuated proliferation, invasion and metastatic and reversed EMT in HCC via PI3K/Akt/HIF-1α/NF-κB/Twist1 pathway by targeting CXCL12. This study proposed that FKA may be a candidate drug and prospective strategy for HCC therapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Proto-Oncogene Proteins c-akt , NF-kappa B , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Liver Neoplasms/pathology , Cell Line, Tumor , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/metabolism , Cell Movement , Epithelial-Mesenchymal Transition , Chemokine CXCL12
6.
Surgery ; 173(2): 537-543, 2023 02.
Article in English | MEDLINE | ID: mdl-36424198

ABSTRACT

BACKGROUND: This study aimed to determine whether the different methods of portal vein reconstruction have an impact on the occurrence of portal vein complications after pediatric living-donor liver transplantation with left lobe graft. METHODS: A total of 567 recipients were eligible for enrollment in this study and were divided into the following 2 groups according to the type of portal vein reconstruction: group 1 underwent anastomosis of the left and right bifurcations of the recipient portal vein to the donor portal vein (type 1), whereas group 2 underwent anastomosis of the bevel formed by the main trunk and right branch of the recipient portal vein to the donor portal vein (type 2). Postoperative portal vein complications and recipient and graft survival rates were compared between the 2 groups before and after propensity score matching. RESULTS: Portal vein complications occurred in 53 (9.3%) patients, including 46 recipients with portal vein stenosis and 7 with portal vein thrombosis. After propensity score matching, the incidence of portal vein stenosis in group 2 was lower than that in group 1 (P = .035). The first diagnosis time of portal vein stenosis in group 2 was later than that in group 1 (P = .033), and the incidence of early portal vein stenosis was lower than that in group 1 (P = .009). There were no statistically significant differences in the incidence of portal vein thrombosis and recipient and graft survival rates between the 2 groups. CONCLUSIONS: Type 2 portal vein reconstruction appears to be a viable technique in pediatric living-donor liver transplantation with left lobe graft that can effectively reduce the incidence of portal vein stenosis.


Subject(s)
Liver Diseases , Liver Transplantation , Venous Thrombosis , Humans , Child , Liver Transplantation/adverse effects , Liver Transplantation/methods , Portal Vein/surgery , Living Donors , Constriction, Pathologic/etiology , Retrospective Studies , Liver Diseases/surgery , Venous Thrombosis/etiology
7.
Liver Transpl ; 29(1): 58-66, 2023 01 01.
Article in English | MEDLINE | ID: mdl-35715984

ABSTRACT

The lower limit of body weight for "splitable" liver grafts remains unknown. To examine the outcome of split-liver transplantation (SLT) from pediatric donors ≤25 kg relative to conventional graft-type liver transplantation from deceased donors under corresponding conditions, a total of 158 patients who received primary liver transplantation, including 22 SLTs from donors ≤25 kg, 46 SLTs from donors >25 kg, 76 whole-liver transplantations, and 14 reduced-liver transplantations in donors ≤25 kg between January 2018 and December 2019, were included in the study. There was no significant difference in the complications, patient survival, and graft survival between each of the latter three groups and the SLT ≤25 kg group. Pediatric End-Stage Liver Disease (PELD) score was the independent predictor of graft loss (death or retransplantation). Graft weight was the independent predictor of hepatic artery thrombosis. SLT using well-selected pediatric donors ≤25 kg is an effective strategy to increase organ availability, especially for low-body-weight recipients, compared with conventional graft type from deceased donors under the condition of corresponding donor weight without increasing morbidity and mortality.


Subject(s)
End Stage Liver Disease , Liver Transplantation , Child , Humans , Liver Transplantation/adverse effects , End Stage Liver Disease/surgery , Treatment Outcome , Severity of Illness Index , Tissue Donors , Graft Survival , Retrospective Studies
8.
J Viral Hepat ; 29(12): 1099-1106, 2022 12.
Article in English | MEDLINE | ID: mdl-36094676

ABSTRACT

We investigated the clinical characteristics and therapeutic strategies for paediatric liver transplant (PLT) recipients who experienced de novo hepatitis B virus infection and the features of HBsAg seroconversion. A total of 821 PLT were performed in HBV-free recipients between January 2013 and January 2019 in Paediatric Organ Transplant Center, Tianjin First Central Hospital. Twenty-one recipients developed de novo HBV infection, the clinical data were analysed. The overall incidence of de novo HBV infection was 2.5%. Only one recipient received an HBcAb-negative graft, 20 recipients received HBcAb-positive grafts. The incidence of de novo HBV infection in HBcAb-negative and HBcAb-positive graft recipients were 0.2% and 6.3%, respectively. Fifteen de novo HBV-infected recipients showed HBsAg seroconversion, the incidence of HBsAg seroconversion was 71.4%. The median time from the diagnosis of de novo HBV infection to HBsAg seroconversion was 15 (1, 73) months. Recipients with hepatitis B surface antigen (HBsAg) titre <1000 IU/L and negative hepatitis B e antigen (HBeAg) at the time of de novo HBV infection diagnosis were more likely to achieve HBsAg seroconversion. Nucleotide analogues were effective in treating recipients with de novo HBV infection. De novo HBV infection does not impact liver graft function as well as recipient and graft survival rate. De novo HBV infection does not impact PLT recipient outcomes under close monitoring and appropriate treatment. High incidence of HBsAg seroconversion can be achieved after anti-viral therapy.


Subject(s)
Hepatitis B , Liver Transplantation , Child , Humans , Hepatitis B Surface Antigens , Hepatitis B virus , Liver Transplantation/adverse effects , Seroconversion , Hepatitis B Core Antigens , Hepatitis B/drug therapy , Hepatitis B/epidemiology , Hepatitis B Antibodies , Antiviral Agents/therapeutic use
9.
J Pediatr Surg ; 57(12): 947-954, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35810021

ABSTRACT

BACKGROUND: Pediatric living-donor liver transplantation (LDLT) has become one of the most effective therapies for pediatric end-stage liver diseases. We aim to investigate the risk factors for intra-operative portal vein thrombosis (PVT) and the short- and long-term outcomes in children post LDLT. METHODS: This was a retrospective analysis from 584 cases of biliary atresia (BA) patients who had undergone LDLT from January 2014 to December 2019 at our hospital. Patients were divided into PVT and non-PVT groups according to the occurrence of PVT during LDLT. RESULTS: The median age of recipients at transplantation was 7.22 (quartiles, 6.03, 9.50) months, the incidence of intra-operative PVT was 5.31% (31/584). The independent risk factors for intra-operative PVT were the diameter of the recipient's PV not greater than 4 mm and a higher ratio of graft-to-recipient PV diameter. The cumulative survival rates of grafts and recipients were 93.5% and 93.5% in the PVT group, and 94.9% and 95.3% in the non-PVT group, respectively, without significant difference. The recovery of graft function was similar in recipients with or without interposed graft vessel (IGV). However, the incidence of PV stenosis was higher in recipients with IGV after LDLT. CONCLUSION: Intra-operative PVT is a common complication in pediatric LDLT, but an excellent prognosis can be achieved by appropriate and individualized surgical treatment. We noted that intra-operative PVT did not affect the survival rates of grafts and recipients, but there was a higher incidence of PV complications after LDLT. LEVEL OF EVIDENCE: Ⅲ.


Subject(s)
Biliary Atresia , Liver Diseases , Liver Transplantation , Venous Thrombosis , Humans , Child , Infant , Living Donors , Liver Transplantation/adverse effects , Biliary Atresia/surgery , Biliary Atresia/complications , Portal Vein/surgery , Retrospective Studies , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology , Liver Diseases/complications , Treatment Outcome
10.
Pediatr Transplant ; 26(7): e14342, 2022 11.
Article in English | MEDLINE | ID: mdl-35735271

ABSTRACT

BACKGROUND: Several surgical strategies, including split donor transplantation and living donor transplantation, have been used to increase the donor liver pool. This report focuses on the effects of whole, split, and LDLT on recipient outcomes. METHODS: We retrospectively analyzed the records of all patients with biliary atresia at Tianjin First Central Hospital between April 2013 and December 2019. RESULTS: A total of 882 patients were included and divided into three groups by graft type, with 198 in the whole-liver-transplantation group, 78 in the split liver transplantation group, and 606 in the LDLT group. The median follow-up time was 39 months, patient survival rates of three groups were 94.4%, 88.5%, and 95.0%, respectively, and graft survival rates were 90.2%, 83.3%, and 94.7%, respectively. We divided the split liver transplantation group into two subgroups according to the donor's age, and patient survival rates exhibited a significant difference only in the group whose donor age was over 45 years. The postoperative complication rates were significantly higher with respect to hepatic artery thrombosis, portal stenosis, and AR; and lower in hepatic venous stenosis, PTLDs, CMV virus, and EBV infection in the WLT group. Our multivariate model showed that donor age ≥45 years, RBC transfusion, pneumonia, and HAT were the independent predictors of allograft loss. CONCLUSIONS: The survival of split liver transplantation group was slightly lower. The types of complications are different from different graft types. Therefore, postoperative monitoring and treatment need to be adjusted according to the different graft types used.


Subject(s)
Biliary Atresia , Liver Transplantation , Allografts , Biliary Atresia/surgery , Child , Constriction, Pathologic , Graft Survival , Humans , Liver Transplantation/methods , Living Donors , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome
11.
J Pediatr Surg ; 57(11): 656-665, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35688691

ABSTRACT

BACKGROUND/PURPOSE: The incidence of hepatic artery thrombosis (HAT) in recipients is high after pediatric LT using young donors. In this study we investigated the management and outcome of HAT after whole-LT using donors less than one year of age. And evaluate the safety of pediatric donors, and increase the utilization of pediatric donors overall. METHODS: We retrospectively analyzed the clinical data encompassing children who underwent whole-liver transplantation in our department from January 2014 to December 2019. Recipients receiving a liver from a donor ≥1 month and ≤12 months were included, and a total of 110 patients were included in this study. RESULTS: The results showed an incidence for HAT of 20% and the median time to HAT diagnosis was 3.0 (2.0, 5.3) days post-operation. Anticoagulant therapy was used for 19 cases and 94.7% of them achieved hepatic artery recanalization or collateral formation. The median time of recanalization was 12 (5, 15) days. Bile leakage and biliary strictures occurring in the HAT group were higher than in the non HAT group (13.6% vs. 1.1% and 31.8% vs. 3.4%). There were no significant differences in the survival rates of recipients or grafts among the two groups (P = 0.474, P = 0.208, respectively). CONCLUSION: We confirmed that the incidence of HAT in LT recipients use donors less than 1 year is high, but recanalization can be performed using anticoagulant therapy. Although biliary complications increased significantly after HAT, the survival rates of patients and grafts were satisfactory. LEVEL OF EVIDENCE: Level III.


Subject(s)
Liver Transplantation , Thrombosis , Anticoagulants/therapeutic use , Child , Hepatic Artery/surgery , Humans , Liver Transplantation/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Thrombosis/epidemiology , Thrombosis/etiology
12.
Surgery ; 172(1): 391-396, 2022 07.
Article in English | MEDLINE | ID: mdl-35210103

ABSTRACT

BACKGROUND: Living donor liver transplantation using the left lateral segment of the liver is the most common type of pediatric liver transplantation. An appropriate surgical approach is crucial for decreasing the risk of vascular complications using these grafts with anatomical variations. METHODS: Between January 2017 and December 2020, 631 living donor liver transplantations using left lateral segment grafts were performed at Tianjin First Central Hospital. The grafts from 162 (25.7%) donors have 2 hepatic vein openings. A total number of 21 transplantations using left lateral segment grafts with 2 widely spaced hepatic vein openings were performed. In group 1, the unification venoplasty technique with interposition vein graft was used at the back table for the reconstruction of hepatic vein from grafts. In group 2, dual hepatic vein reconstructions were performed, in which venoplasty of recipients' left hepatic vein, middle hepatic vein, and inferior vena cava was performed to create a large orifice for anastomosis with segment Ⅱ hepatic vein from the graft. Segment III hepatic vein from the graft was anastomosed with the recipient's right hepatic vein. The incidence, treatment, and outcomes of hepatic venous outflow obstruction were compared between the 2 groups. RESULTS: The median follow-up time was 12.8 months. There was no significant difference in the incidence of hepatic venous outflow obstruction between the 2 groups. CONCLUSION: Dual hepatic vein reconstruction is an alternate surgical option for grafts with 2 widely spaced hepatic veins, and it is associated with ideal graft recovery and vascular condition. However, long-term follow-up is still needed to verify the efficacy and safety of this approach.


Subject(s)
Budd-Chiari Syndrome , Liver Transplantation , Child , Hepatic Veins/surgery , Humans , Liver Transplantation/methods , Living Donors , Vena Cava, Inferior/surgery
13.
Cancer Innov ; 1(2): 124-134, 2022 Aug.
Article in English | MEDLINE | ID: mdl-38090650

ABSTRACT

Background: Kidney cancer originates from the urinary tubule epithelial system of the renal parenchyma, accounting for 20% of all urinary system tumors. Approximately 70% of cases are localized at diagnosis, and 30% are metastatic. Most localized kidney cancers can be cured by surgery, but most metastatic patients relapse after surgery and eventually die of kidney cancer. Therefore, accurately predicting patient survival and identifying high-risk metastatic patients will effectively guide interventions and improve prognosis. Methods: This study used the data of 12,394 kidney cancer patients from the surveillance, epidemiology, and end results database to construct a research cohort related to kidney cancer survival and metastasis. Eight machine learning models (including support vector machines, logistic regression, decision tree, random forest, XGBoost, AdaBoost, K-nearest neighbors, and multilayer perceptron) were developed to predict the survival and metastasis of kidney cancer and six evaluation indicators (accuracy, precision, sensitivity, specificity, F1 score, and area under the receiver operating characteristic [AUROC]) were used to verify, evaluate, and optimize the models. Results: Among the eight machine learning models, Logistic Regression has the highest AUROC in both prediction scenarios. For 3-year survival prediction, the Logistic Regression model had an accuracy of 0.684, a sensitivity of 0.702, a specificity of 0.670, a precision of 0.686, an F1 score of 0.683, and an AUROC of 0.741. For tumor metastasis prediction, the Logistic Regression model had an accuracy of 0.800, a sensitivity of 0.540, a specificity of 0.830, a precision of 0.769, an F1 score of 0.772, and an AUROC of 0.804. Conclusion: In this study, we selected appropriate variables from both statistical and clinical significance and developed and compared eight machine learning models for predicting 3-year survival and metastasis of kidney cancer. The prediction results and evaluation results demonstrated that our model could provide decision support for early intervention for kidney cancer patients.

14.
Pediatr Transplant ; 26(1): e14123, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34428333

ABSTRACT

BACKGROUND: The aim of this study was to analyze the risk factors, causes, and management of intestinal obstruction after pediatric liver transplantation. METHODS: Retrospective analysis was performed on pediatric liver transplantation recipients from January 1st 2013 to December 31st 2019 at Organ Transplant Center, Tianjin First Central Hospital. The cases of intestinal obstruction were analyzed. RESULTS: A total of 1034 pediatric liver transplantations were performed during the study period, 66 intestinal obstructions were diagnosed in 61 recipients. Three recipients suffered intestinal obstructions twice, and one recipient suffered three times. Forty of the 66 cases were treated with non-surgical treatment, including fasting, gastrointestinal decompression, purgation, enema, and parenteral nutrition. Surgical intervention was performed in 26 cases. Diaphragmatic hernia, intestinal inflammatory stenosis, PTLD, and intestine perforation are essential causes of intestinal obstruction in pediatric liver transplant recipients. Diaphragmatic hernia was independent risk factors for intestinal obstruction. The 1-, 2- and 3-year survival rate of the recipients with or without intestinal obstruction were 98.4%, 96.5%, 96.5% and 95.3%, 94.4%, 94.0%, respectively, without significant difference. CONCLUSIONS: Most cases of intestinal obstruction after liver transplantation in children can be remitted by non-surgical treatment, but there are still some cases need to be treated by surgery. Both measures are related to ideal outcomes, intestinal obstruction does not increase the mortality rate in pediatric liver transplantation.


Subject(s)
Intestinal Obstruction , Liver Transplantation , Postoperative Complications , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Intestinal Obstruction/diagnosis , Intestinal Obstruction/etiology , Intestinal Obstruction/therapy , Male , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/therapy , Retrospective Studies , Risk Factors , Treatment Outcome
15.
Arch Gerontol Geriatr ; 99: 104588, 2022.
Article in English | MEDLINE | ID: mdl-34906886

ABSTRACT

BACKGROUND: Recent studies have revealed the close correlation between microRNAs (miRs) and Parkinson's disease (PD). Here, we aimed to investigate the neuroprotective effect of miR-124 in a PD mouse model. METHODS: MiR-124 expression in human plasma was detected by qRT-PCR. PD mouse model was established by stereotactic injection of 6-hydroxydopmine. Lentivirus were used to deliver and overexpress miR-124 and Axin1 into the substantia nigra. Multiple behavioral tests and oxidative stress assays were carried out to access the protective effect of miR-124 against PD. Western blot and luciferase assay were conducted to dissect the underlying molecular mechanisms. RESULTS: MiR-124 expression was decreased in PD patients. Overexpression of miR-124 in PD mice could improve motor defects, ameliorate dopaminergic neurons loss, and reduce oxidative stress. Mechanistically, miR-124 targeted Axin1 directly, and then attenuated PD progression via suppressing Axin1 and activating the Wnt/ß-catenin pathways in PD mice. CONCLUSION: MiR-124 is an important neuroprotective factor, which suppresses Axin1 and activates Wnt/ß-catenin signaling pathways in PD mice.


Subject(s)
MicroRNAs , Neuroprotective Agents , Parkinson Disease , Animals , Disease Models, Animal , Dopaminergic Neurons/metabolism , Humans , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Neuroprotective Agents/metabolism , Parkinson Disease/genetics , Wnt Signaling Pathway/genetics
16.
J Cell Mol Med ; 25(24): 11185-11197, 2021 12.
Article in English | MEDLINE | ID: mdl-34747105

ABSTRACT

Liver fibrosis is the repair process of abnormal connective tissue hyperplasia after liver damage caused by different causes. Inhibition of PI3K/Akt signalling pathway can reduce the deposition of extracellular matrix, inhibit the proliferation of hepatic stellate cells (HSCs), and promote its apoptosis to achieve the purpose of therapy. This study aimed to investigate the effect of Idelalisib (PI3K inhibitor) on carbon tetrachloride (CCl4 )-induced liver fibrosis in mice. We used CCl4 -induced liver fibrosis mouse model in vivo and TGF-ß1-stimulated HSCs to evaluate the antifibrosis activity of Idelalisib. In vivo, Idelalisib significantly alleviated CCl4 -induced liver damage, collagen deposition, and hydroxyproline accumulation in mice. Immunohistochemistry and Western blot results showed that Idelalisib could significantly inhibit the expressions of COL1 and α-SMA in a concentration-dependent manner. In cell experiments, Idelalisib significantly inhibited the expressions of COL1, SMA, and p-Smad3 in TGF-ß-induced HSCs, thereby inhibiting HSC activation. Flow cytometry and Western blot results showed that Idelalisib significantly promoted TGFß-induced apoptosis of HSCs after 48 h of administration, but had no significant effect after 24 h. Idelalisib promoted the apoptosis of activated HSCs by inhibiting the PI3K/Akt/FOXO3 signalling pathway. To further explore the mechanism by which Idelalisib inhibited PI3K, we predicted the miRNA targeting PI3K through the database and crossed it with the down-regulated miRNA reported in liver fibrosis mice in the past five years. Finally, we identified miR-124-3p and miR-143-3p. We then demonstrated that Idelalisib significantly promoted miR-124-3p and miR-142-3p in vitro and in vivo. Dual-luciferase report analysis showed that Idelalisib significantly inhibited luciferase activity but had no significant effect on the luc-MUT transfection assay. Finally, we demonstrated that Idelalisib reversed the effects of miR-124-3p inhibitor on the PI3K/Akt/FOXO3 asterisk pathway and caspase-3. Idelalisib has potential as a candidate drug for alleviating liver fibrosis.


Subject(s)
Gene Expression Regulation/drug effects , Liver Cirrhosis/etiology , Liver Cirrhosis/metabolism , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , Purines/pharmacology , Quinazolinones/pharmacology , Signal Transduction/drug effects , Animals , Apoptosis/drug effects , Biomarkers , Biopsy , Carbon Tetrachloride/adverse effects , Disease Models, Animal , Disease Susceptibility , Extracellular Matrix , Forkhead Box Protein O3/metabolism , Hepatic Stellate Cells/metabolism , Immunohistochemistry , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Male , Mice , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Phosphorylation
17.
Liver Transpl ; 27(1): 96-105, 2021 01.
Article in English | MEDLINE | ID: mdl-32511854

ABSTRACT

The goal of this study was to evaluate the efficacy of a perioperative prophylactic strategy against de novo hepatitis B virus (HBV) infection in pediatric liver transplantation (LT) recipients with hepatitis B core antibody (HBcAb)-positive grafts. A total of 482 pediatric recipients transplanted between 2013 and 2017 were enrolled, and 170 recipients received HBcAb-positive liver grafts. The overall graft and recipient survival rates in HBcAb-positive and HBcAb-negative graft recipients were 91.8% versus 91.3% and 95.3% versus 94.2% at the end of follow-up. Preoperative hepatitis B surface antibody (HBsAb) titer ≥ 1000 IU/L and postoperative HBsAb titer ≥200 IU/L were our prophylactic targets for recipients receiving HBcAb-positive grafts. While 11 recipients developed de novo HBV infection, 10 received HBcAb-positive grafts. Both the preoperative and postoperative HBsAb targets were achieved in 78 recipients, the infection rate of de novo HBV was 1.3%; 24 recipients met the preoperative target, the infection rate was 4.2%; 52 recipients met the postoperative target, the infection rate was 1.9%; and 16 recipients met neither the preoperative nor postoperative HBsAb target, 43.8% of the recipients were infected with de novo HBV, which was significantly higher than the recipients who met both or either of the preoperative and postoperative targets. Split-liver grafts positive for HBcAb showed higher risk of de novo HBV infection. Postoperative application of lamivudine to recipients whose preoperative HBsAb titer < 1000 IU/L did not show preventive effect. Out of 11 infected recipients, 3 showed seroconversion under entecavir treatment. In conclusion, the graft and recipient survival rates were similar in pediatric LT recipients receiving HBcAb-positive or HBcAb-negative grafts. Our prophylactic strategy was effective for preventing de novo HBV infection in HBcAb-positive liver graft recipients.


Subject(s)
Hepatitis B , Liver Transplantation , Child , Hepatitis B/prevention & control , Hepatitis B Antibodies , Hepatitis B Core Antigens , Hepatitis B Surface Antigens , Hepatitis B virus , Humans , Liver Transplantation/adverse effects , Retrospective Studies
18.
Sensors (Basel) ; 20(22)2020 Nov 18.
Article in English | MEDLINE | ID: mdl-33218098

ABSTRACT

Orthogonal frequency division multiplexing (OFDM) chirp waveform, which is composed of two or more successive identical linear frequency modulated sub pulses, is a newly proposed orthogonal waveform scheme for multi-input multi-output (MIMO) synthetic aperture radar (SAR) systems. However, according to the waveform model, there will be range ambiguity if the mapping width exceeds the maximum unambiguous width determined by the transmitted signal. This greatly limits its application in high-resolution wide-swath (HRWS) remote sensing. The traditional system divides the echoes by digital beam forming (DBF) to solve this problem, but the energy utilization rate is low. A MIMO-SAR system using simultaneous digital beam forming of both transceiver and receiver to avoid range ambiguity is designed in this paper. Compared with traditional system, the novel system designed in this paper obtain higher energy utilization and waveform orthogonality.

19.
Pediatr Surg Int ; 36(12): 1443-1450, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33040172

ABSTRACT

PURPOSE: To investigate the efficacy of living donor liver transplantation (LDLT) plus domino-auxiliary partial orthotopic liver transplantation (D-APOLT) in pediatric patients with metabolic disorders. METHODS: From May 2017 to October 2018, two patients with ornithine aminotransferase deficiency (OTCD) and one patient with type I Crigler-Najjar syndrome (CNS1) received LDLT, their livers were prepared as donors for D-APOLT. Two patients with CNS1 received domino liver grafts from OTCD patients; one OTCD patient received a domino liver graft from a CNS1 patient. RESULTS: The mean follow-up was 26.6 months. The liver function and ammonia remained in the normal range at the end of the follow-up in all recipients. One D-APOLT patient experienced portal vein thrombosis 2 days after transplantation and required reoperation, this patient presented an imbalance of portal blood perfusion between the native and the domino liver at 8 months after liver transplant. The imbalance was improved by interventional radiology treatment. Two LDLT patients experienced early mild acute rejection. CONCLUSIONS: The non-cirrhotic livers from pediatric patients with metabolic liver disease can be used as domino donor grafts for selected pediatric patients with different metabolic liver disease. D-APOLT achieves ideal recipient outcomes and provides a strategy to expand donor source for children.


Subject(s)
Liver Diseases/complications , Liver Diseases/surgery , Liver Transplantation/methods , Living Donors , Metabolic Diseases/complications , Metabolic Diseases/surgery , Adult , Child , Child, Preschool , Feasibility Studies , Female , Follow-Up Studies , Humans , Liver/surgery , Male , Prospective Studies , Reoperation , Retrospective Studies
20.
Opt Express ; 28(13): 19113-19125, 2020 Jun 22.
Article in English | MEDLINE | ID: mdl-32672195

ABSTRACT

A microwave photonic (MWP) radar with a fiber-distributed antenna array for three-dimensional (3D) imaging is proposed and demonstrated for the first time. Photonic frequency doubling, wavelength-division multiplexing and radio-over-fiber techniques are employed for radar signal generation, replication, and distribution. Based on the delay-dependent beat frequency division, parallel de-chirp processing is completed in the center office (CO), leading to multi-channel 2D ISAR imaging and further 3D reconstruction. The influence of the fiber transmission delay is discussed and the phase noise caused thereby is compensated in 3D imaging algorithm, improving the coherence between channels. An experiment of a Ku-band MWP radar with a transmitter (Tx) and 16 equivalent receivers (Rxs) is conducted and 3D imaging of three trihedral corner reflectors is achieved with a range resolution of 7.3 cm, a cross-rage resolution of 5.6 cm and an elevation resolution of 0.85°. The results verify the capability of MWP radar in high-resolution 3D imaging.

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