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2.
Adv Mater ; 36(16): e2311970, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38198824

RESUMO

[4-(3,6-dimethyl-9H-carbazol-9yl)butyl]phosphonic acid (Me-4PACz) self-assembled molecules (SAM) are an effective method to solve the problem of the buried interface of NiOx in inverted perovskite solar cells (PSCs). However, the Me-4PACz end group (carbazole core) cannot forcefully passivate defects at the bottom of the perovskite film. Here, a Co-SAM strategy is employed to modify the buried interface of PSCs. Me-4PACz is doped with phosphorylcholine chloride (PC) to form a Co-SAM to improve the monolayer coverage and reduce leakage current. The phosphate group and chloride ions (Cl-) in PC can inhibit NiOx surface defects. Meantime, the quaternary ammonium ions and Cl- in PC can fill organic cations and halogen vacancies in the perovskite film to enable defects passivation. Moreover, Co-SAM can promote the growth of perovskite crystals, collaboratively solve the problem of buried defects, suppress nonradiative recombination, accelerate carrier transmission, and relieve the residual stress of the perovskite film. Consequently, the Co-SAM modified devices show power conversion efficiencies as high as 25.09% as well as excellent device stability with 93% initial efficiency after 1000 h of operation under one-sun illumination. This work demonstrates the novel approach for enhancing the performance and stability of PSCs by modifying Co-SAM on NiOx.

3.
Trials ; 24(1): 774, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037035

RESUMO

BACKGROUND: Our previous randomized controlled trial (RCT) have demonstrated that intermittent Pringle's maneuver (IPM) with a 25-min ischemic interval can be applied safely and efficiently in open or laparoscopic hepatectomy in patients with hepatocellular carcinoma (HCC) patients. But prolonging the hepatic inflow blocking time will inevitably aggravate the ischemia-reperfusion injury (IRI) caused by systemic response. This RCT aims to evaluate the effect of administration of dexamethasone versus placebo before clamping the hilar pedicle on postoperative liver function, inflammatory response, and perioperative outcomes among HCC patients undergoing liver resection with 25-min hepatic inflow occlusion. METHODS AND ANALYSIS: This will be a randomized, dual-arm, parallel-group, double-blinded trial. All eligible and consecutive patients are coming from a regional medical center who are diagnosed with HCC and underwent radical R0/R1 resection. All participates are randomly allocated in dexamethasone group or placebo group. All surgeons, anesthesiologists, and outcome assessors will be blinded to allocation status. Primary endpoints are transaminase-based postoperative hepatic injury on seven consecutive days after surgery and assessed by their peak values as well as area under the curve (AUC) of the postoperative course of aminotransferases. Secondary endpoints are postoperative total bilirubin (TBil), coagulation function, inflammatory cytokines and their respective peaks, intraoperative blood loss, postoperative hospital stay, morbidity, and mortality. The above parameters will be compared using the corresponding statistical approach. Subgroup analysis will be performed according to the liver cirrhosis and major hepatectomy. DISCUSSION: Based on our previous study, we will explore further the effect of glucocorticoid administration on attenuating the surgical stress response in order to follow securely 25-min hepatic inflow occlusion. Therefore, the trial protocol is reasonable and the results of the trial may be clinically significant. TRIAL REGISTRATION: This trial was registered on 3 December 2022, in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR2200066381. The protocol version is V1.0 (20221104).


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Perda Sanguínea Cirúrgica , Carcinoma Hepatocelular/cirurgia , Dexametasona/uso terapêutico , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Front Microbiol ; 14: 1219763, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37649633

RESUMO

Introduction: Obesity and diabetes are common chronic metabolic disorders which can cause an imbalance of the intestinal flora and gut-liver metabolism. Several studies have shown that probiotics, including Escherichia coli Nissle 1917 (EcN), promote microbial balance and metabolic health. However, there are no studies on how EcN outer membrane vesicles (EcN-OMVs) influence the intestinal microflora and affect the metabolic disorders of obesity and diabetes. Methods: In this study, we evaluated the effects of EcN-OMVs on high-fat diet (HFD)-induced obesity and HFD + streptozotocin (STZ)-induced diabetes. Results: EcN-OMVs could reduce body weight, decrease blood glucose, and increase plasma insulin in obese mice. Similarly, EcN-OMVs treatment could modify the ratio of Firmicutes/Bacteroidetes in the gut, elevate intestinal short-chain fatty acid (SCFA)-producing flora, and influence the SCFA content of the intestine. Furthermore, the intestinal metabolites ornithine and fumaric acid, hepatic ω-6 unsaturated fatty acids, and SCFAs were significantly increased after administering EcN-OMVs. Discussion: Overall, this study showed that EcN-OMVs might act as post-biotic agents that could modulate gut-liver metabolism and ameliorate the pathophysiology of obesity and diabetes.

5.
BMC Surg ; 23(1): 100, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37118720

RESUMO

AIMS: To determine the relationship between microvascular invasion (MVI) and the clinical features of hepatocellular carcinoma (HCC) and provide a method to evaluate MVI status by neutral network analysis. METHODS: The patients were divided into two groups (MVI-positive group and MVI-negative group). Univariate analysis and multivariate logistic regression analysis were carried out to identify the independent risk factors for MVI positivity. Neural network analysis was used to analyze the different importance of the risk factors in MVI prediction. RESULTS: We enrolled 1697 patients in this study. We found that the independent prognostic factors were age, NEU, multiple tumors, AFP level and tumor diameter. By neural network analysis, we proposed that the level of AFP was the most important risk factor for HCC in predicting MVI status (the AUC was 0.704). However, age was the most important risk factor for early-stage HCC with a single tumor (the AUC was 0.605). CONCLUSION: Through the neutral network analysis, we could conclude that the level of AFP is the most important risk factor for MVI-positive patients and the age is the most important risk factor for early-stage HCC with a single tumor.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas , Estudos Retrospectivos , Invasividade Neoplásica
6.
Clin Immunol ; 251: 109325, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37030526

RESUMO

Ischemia-reperfusion injury (IRI) is one of the most common complications in liver transplantation. METTL3 regulates inflammation and cellular stress response by modulating RNA m6A modification level. Here, the study aimed to investigate the role and mechanism of METTL3 in IRI after rat orthotopic liver transplantation. The total RNA m6A modification and METTL3 expression level was consistently down-regulated after 6 h or 24 h reperfusion in OLT, which is negatively associated with the hepatic cell apoptosis. Functionally, METTL3 pretreatment in donor significantly inhibited liver grafts apoptosis, improved liver function and depressed the proinflammatory cytokine/chemokine expression. Mechanistically, METTL3 inhibited apoptosis of grafts via upregulating HO-1. Moreover, m6A dot blot and MeRIP-qPCR assay revealed that METTL3 promoted HO-1 expression in an m6A-dependent manner. In vitro, METTL3 alleviated hepatocytes apoptosis by upregulating HO-1 under hypoxia/reoxygenation condition. Taken together, these findings demonstrate that METTL3 ameliorates rat OLT-stressed IRI by inducing HO-1 in an m6A-dependent manner, highlighting a potential target for IRI in liver transplantation.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Ratos , Animais , Transplante de Fígado/efeitos adversos , Fígado/metabolismo , Inflamação/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , RNA/metabolismo
7.
Nat Commun ; 14(1): 1342, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906625

RESUMO

Encapsulation engineering is an effective strategy to improve the stability of perovskite solar cells. However, current encapsulation materials are not suitable for lead-based devices because of their complex encapsulation processes, poor thermal management, and inefficient lead leakage suppression. In this work, we design a self-crosslinked fluorosilicone polymer gel, achieving nondestructive encapsulation at room temperature. Moreover, the proposed encapsulation strategy effectively promotes heat transfer and mitigates the potential impact of heat accumulation. As a result, the encapsulated devices maintain 98% of the normalized power conversion efficiency after 1000 h in the damp heat test and retain 95% of the normalized efficiency after 220 cycles in the thermal cycling test, satisfying the requirements of the International Electrotechnical Commission 61215 standard. The encapsulated devices also exhibit excellent lead leakage inhibition rates, 99% in the rain test and 98% in the immersion test, owing to excellent glass protection and strong coordination interaction. Our strategy provides a universal and integrated solution for achieving efficient, stable, and sustainable perovskite photovoltaics.

8.
HPB (Oxford) ; 25(5): 497-506, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36809863

RESUMO

BACKGROUND: This study aimed to find effective treatments for the patient within UCSF criteria. METHODS: This study enrolled 1006 patients meeting UCSF criteria, undergoing hepatic resection (HR), divided into two groups: single tumor group and multiple tumors group. We compared and analyzed the risk factors between these two groups' long-term outcomes, through log-rank test, cox proportional hazards model and using neural network analysis to identify the independent risk factors. RESULTS: The 1-, 3-, and 5-year OS rates in single tumor were significantly higher than multiple tumors (95.0%, 73.2% and 52.3% versus 93.9%, 69.7% and 38.0%, respectively, p < 0.001). The 1-, 3- and 5-year RFS rates were 90.3%, 60.7%, and 40.1% in single tumor and 83.4%, 50.7% and 23.8% in multiple tumors, respectively (p < 0.001). And tumor type, anatomic resection and MVI were the independent risk factors for the patient within UCSF criteria. MVI was the most important risk factor affecting OS and RFS rates in neural network analysis. The method of hepatic resection and the number of tumors were also affected OS and RFS rates. CONCLUSION: Anatomic resections should be applied to patients within UCSF criteria, especially for patients with single MVI negative tumours.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Hepatectomia/efeitos adversos , São Francisco , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia
9.
Front Genet ; 13: 944278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36437956

RESUMO

Background: Dysregulation of long non-coding (lncRNA) has been reported in various solid tumors. HOXA cluster antisense RNA 2 (HOXA-AS2) is a newly identified lncRNA with abnormal expression in several human malignancies. However, its prognostic value remains controversial. This meta-analysis synthesized available data to clarify the association between HOXA-AS2 expression levels and clinical prognosis in multiple cancers. Methods: Four public databases (Embase, PubMed, Web of Science, The Cochrane Library) were used to identify eligible studies. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined to assess the correlation of HOXA-AS2 expression with survival outcomes and clinicopathological features of cancer patients. Publication bias was measured using Begg's funnel plot and Egger's regression test, and the stability of the combined results was measured using sensitivity analysis. Additionally, multiple public databases were screened and extracted to validate the results of this meta-analysis. Results: The study included 20 studies, containing 1331 patients. The meta-analysis showed that the overexpression of HOXA-AS2 was associated with poor overall survival (HR = 2.06, 95% CI 1.58-2.69, p < 0.001). In addition, the high expression of HOXA-AS2 could forecast advanced tumor stage (OR = 3.89, 95% CI 2.90-5.21, p < 0.001), earlier lymph node metastasis (OR = 3.48, 95% CI 2.29-5.29, p < 0.001), larger tumor size (OR = 2.36, 95% CI 1.52-3.66, p < 0.001) and earlier distant metastasis (OR = 3.54, 95% CI 2.00-6.28, p < 0.001). However, other clinicopathological features, including age (OR = 1.09, 95% CI 0.86-1.38, p = 0.467), gender (OR = 0.92, 95% CI 0.72-1.18, p = 0.496), depth of invasion (OR = 2.13, 95% CI 0.77-5.90, p = 0.146) and differentiation (OR = 1.02, 95% CI 0.65-1.59, p = 0.945) were not significantly different from HOXA-AS2 expression. Conclusion: Our study showed that the overexpression of HOXA-AS2 was related to poor overall survival and clinicopathological features. HOXA-AS2 may serve as a potential prognostic indicator and therapeutic target for tumor treatment.

10.
Medicina (Kaunas) ; 58(9)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36143956

RESUMO

Background and Objective: The study aims to investigate the correlation between Hepatitis B 'e' antigen (HBeAg) and HBV DNA levels, and to find a convenient tool to estimate the HBV DNA level for clinicians. Materials and Methods: We enrolled 1020 patients in this cross-sectional study and divided them into four groups: an HbeAg-positive and -negative group, and high and low HBV DNA levels groups. Results: Alanine aminotransferase (ALT), Albumin (ALB) and HBeAg are independent risk factors for CHB patients. When the level of HBeAg is higher than 16.15 S/CO, it is four times more likely that the patients will have high levels of HBV DNA than those who do not. The ALT and TB are independent risk factors in HBeAg-negative patients with a high HBV DNA level. We have drawn three predictive models to estimate the HBV DNA levels for those with the chronic hepatitis B virus (CHB), and those that are HBeAg-positive and HBeAg-negative (Y1 = 0.004 × ALT(IU/L) + 1.412 × HBeAg (S/CO) - 0.029 × ALB (g/L) + 0.779, the AUC is 0.672, and the cutoff value is -0.072, there the sensitivity is 0.615, the specificity is 0.648, PPV is 65.182% and NPV is 60.837%; Y2 = 0.007 × HBeAg (S/CO) - 0.016 × HGB (g/L) + 3.070, the AUC is 0.724, and the cutoff value is 1.216, where the sensitivity is 0.626, the specificity is 0.897, PPV is 94.118% and NPV is 34.437%; Y3 = -0.005 × ALT(IU/L) + 0.006 × TB (umol/L) + 0.385, the AUC is 0.661, and the cutoff value is 0.263, where the sensitivity is 0.677, the specificity is 0.587, PPV is 66.820% and NPV is 40.774%, respectively). We propose that HBeAg is the most important risk factor for the patient with a high HBV DNA level, however, it is not as important in the HBeAg-positive group. Conclusions: HBeAg is an independent risk factor that reflects the level of HBV DNA with a strong correlation. Patient with HBeAg (-) should combine TB and ALT to estimate the level of HBV DNA.


Assuntos
Antígenos E da Hepatite B , Hepatite B Crônica , Alanina Transaminase , Albuminas , Estudos Transversais , DNA Viral , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Humanos
12.
Front Immunol ; 13: 932303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967354

RESUMO

Pyroptosis, a way of pro-inflammatory death, plays a significant part in the tumor microenvironment (TME). A recent study has shown that the hepatitis C virus changes the TME by inducing pyroptosis against hepatocellular carcinoma (HCC). However, compared to TME in hepatitis C virus-infected HCC, the exploration of immune characteristics and response to immunotherapy associated with the pyroptosis phenotype is still insufficient in hepatitis B virus-related HCC (HBV-HCC). Our study constructed pyroptosis-score (PYS) via principal-component analysis (PCA) to unveil the link between pyroptosis and tumor immunity in 369 HBV-HCC patients. Compared with the low-PYS group, subjects with higher PYS were associated with poor prognosis but were more susceptible to anti-PD-L1 treatment. In addition, we found that PYS can serve independently as a prognostic factor for HBV-HCC, making it possible for us to identify specific small molecule drugs with a potential value in inhibiting tumors via targeting pyroptosis. Also, the target genes predicted by the Weighted gene co-expression network analysis (WGCNA) and pharmacophore model were enriched in the HIF-1 signaling pathway and NF-kB transcription factor activity, which were related to the mechanism of inflammation-driven cancer. The PYS is extremely important in predicting prognosis and responses to immunotherapy. New treatment strategies for inflammation-driven cancers may be found by targeting pyroptosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Genômica , Vírus da Hepatite B/genética , Humanos , Inflamação , Neoplasias Hepáticas/patologia , Piroptose/genética , Microambiente Tumoral/genética
13.
Front Immunol ; 13: 823511, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35603144

RESUMO

Neutrophil extracellular traps (NETs) play important roles in hepatic ischemic reperfusion injury (IRI) and acute rejection (AR)-induced immune responses to inflammation. After liver transplantation, HMGB1, an inflammatory mediator, contributes to the development of AR. Even though studies have found that HMGB1 can promote NET formation, the correlation between NETs and HMGB1 in the development of AR following liver transplantation has not been elucidated. In this study, levels of serum NETs were significantly elevated in patients after liver transplantation. Moreover, we found that circulating levels of NETs were negatively correlated with liver function. In addition, liver transplantation and elevated extracellular HMGB1 promoted NET formation. The HMGB1/TLR-4/MAPK signaling pathway, which is initiated by HMGB1, participates in NET processes. Moreover, in the liver, Kupffer cells were found to be the main cells secreting HMGB1. NETs induced Kupffer cell M1 polarization and decreased the intracellular translocation of HMGB1 by inhibiting DNase-1. Additionally, co-treatment with TAK-242 (a TLR-4 inhibitor) and rapamycin more effectively alleviated the damaging effects of AR following liver transplantation than either drug alone.


Assuntos
Armadilhas Extracelulares , Proteína HMGB1 , Transplante de Fígado , Armadilhas Extracelulares/metabolismo , Rejeição de Enxerto , Proteína HMGB1/metabolismo , Humanos , Células de Kupffer/metabolismo , Fígado/metabolismo , Neutrófilos , Receptor 4 Toll-Like/metabolismo
14.
Zhongguo Gu Shang ; 35(5): 409-17, 2022 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-35535527

RESUMO

OBJECTIVE: To analyze the difference in clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant channel system combined with microscope and percutaneous pedicle screw in the treatment of degenerative lumbar spondylolisthesis. METHODS: A total of 114 patients with single-segment degenerative lumbar spondylolisthesis from June 2015 to February 2019, were divided into three groups according to the surgical methods, such as the MIS-TLIF under the microscope surgery group ( microscope group), MIS-TLIF combined with percutaneous pedicle screw technique surgery group(percutaneous group) and posterior lumbar interbody fusion surgery group (open group). In the microscope group, there were 12 males and 26 females, aged from 42 to 83 years with an average of (63.29±9.09) years. In the percutaneous group, there were 16 males and 22 females, aged from 45 to 82 years with an average of (63.37±7.50) years. In the open group, there were 12 males and 26 females, aged from 51 to 82 years with an average of (63.76±8.21) years. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage, length of surgical incision, frequency of intraoperative fluoroscopy and postoperative time of lying in bed were recorded to analyze the differences in surgical related indicators. Visual analogue scale (VAS) of waist and leg pain in preoperative and postoperative period (3 days, 3 months, 6 months and 12 months) were recorded to evaluate pain remission;Oswestry Disability Index(ODI), Japanese Orthopaedic Association (JOA) score were recorded to evaluate the recovery of waist and leg function on preoperative and postoperative 12 months. The lumbar spondylolisthesis rate and intervertebral height at 12 months after operation were recorded to evaluate the reduction of spondylolisthesis. The Siepe intervertebral fusion standard was used to analyze the intervertebral fusion rate at 12 months after operation. RESULTS: ①All 114 patients were followed up more than 1 year, and no complications related to incision infection occurred. In the microscope group, there was 1 case of subcutaneous effusion 8 days after operation. After percutaneous puncture and drainage, waist compression, and then the healing was delayed. In the percutaneous group, 2 cases of paravertebral muscle necrosis occurred on the side of decompression, and the healing was delayed after debridement. In open group, there was 1 case of intraoperative dural tear, which was packed with free adipose tissue during the operation. There was no postoperative cerebrospinal fluid leakage and other related complications.① Compared with microscope group, percutaneous group increased in operation time, intraoperative blood loss, postoperative wound drainage, surgical incision length, intraoperative fluoroscopy times, and postoperative bed rest time. In open group, intraoperative blood loss, postoperative wound drainage, surgical incision length, and postoperative bed rest time increased, but the intraoperative fluoroscopy time decreased. Compared with percutaneous group, the intraoperative blood loss, wound drainage, surgical incision length, and postoperative bed rest time in open group increased, but operative time and the intraoperative fluoroscopy time decreased(P<0.05). ②ODI and JOA scores of the three groups at 12 months after operation were improved compared with those before operation (P<0.05), but there was no significant difference between the three group(P>0.05). ③Compared with microscope group, the VAS of low back pain in percutaneous group increased at 3 days after operation, and VAS of low back pain in open group increased at 3 days, and 12 month after operation. Compared with percutaneous group, the VAS low back pain score of the open group increased at 3 months after operation (P<0.05). ④ The lumbar spondylolisthesis rate of the three groups of patients at 12 months afrer operation was decreased compared with that before operation(P<0.05), and the intervertebral heigh was increased compared with that before operation(P<0.05), however, there was no significant difference among three groups at 12 months afrer operation(P>0.05). ⑤ There was no significant difference between three groups in the lumbar fusion rate at 12 months afrer operation(P>0.05). CONCLUSION: The MIS-TLIF assisted by microscope and the MIS-TLIF combined with percutaneous pedicle screw are safe and effective to treat the degenerative lumbar spondylolisthesis with single-segment, and the MIS-TLIF assisted by microscope may be more invasive, cause less blood loss and achieve better clinical efficacy.


Assuntos
Dor Lombar , Fusão Vertebral , Espondilolistese , Ferida Cirúrgica , Perda Sanguínea Cirúrgica , Estudos de Casos e Controles , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Hemorragia Pós-Operatória , Estudos Retrospectivos , Fusão Vertebral/métodos , Espondilolistese/cirurgia , Resultado do Tratamento
15.
Angew Chem Int Ed Engl ; 61(18): e202116534, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35174939

RESUMO

The performance enhancement of inverted perovskite solar cells applying nickel oxide (NiOx ) as the hole transport layer (HTL) has been limited by impurity ions (such as nitrate ions). Herein, we have proposed a strategy to obtain high-quality NiOx nanoparticles via an ionic liquid-assisted synthesis method (NiOx -IL). Experimental and theoretical results illustrate that the cation of the ionic liquid can inhibit the adsorption of impurity ions on nickel hydroxide through a strong hydrogen bond and low adsorption energy, thereby obtaining NiOx -IL HTL with high conductivity and strong hole-extraction ability. Importantly, the removal of impurity ions can effectively suppress the redox reaction between the NiOx film and the perovskite film, thus slowing down the deterioration of device performance. Consequently, the modified inverted device shows a striking efficiency exceeding 22.62 %, and superior stability maintaining 92 % efficiency at a maximum power point tracking under one sun illumination for 1000 h.

16.
Hepatobiliary Pancreat Dis Int ; 21(4): 378-386, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35033448

RESUMO

BACKGROUND: Transcription factor 3 (TCF3) plays pivotal roles in embryonic development, stem cell maintenance and carcinogenesis. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. This study aimed to analyze the correlation between TCF3 expression and clinicopathological features of HCC, and further explore the underlying mechanism in HCC progression. METHODS: The expression of TCF3 was collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) HCC datasets, and further confirmed by immunostaining and Western blotting assays. The correlation between TCF3 expression and the clinicopathological features was evaluated. Bioinformatical analysis and in vitro experiments were conducted to explore the potential role of TCF3 in HCC development. RESULTS: Both the mRNA and protein levels of TCF3 were significantly higher in HCC tumor tissues compared to tumor adjacent tissues (P < 0.001 and P < 0.01). Analysis based on TCGA datasets showed that TCF3 was positively correlated with tumor clinical stage and grade, and patients with high TCF3 expression had shorter overall survival (P = 0.012), disease-specific survival (P = 0.022) and progression-free survival (P = 0.013). Similarly, the immunostaining results revealed that the high expression of TCF3 was closely correlated with tumor size (P = 0.001) and TNM stage (P = 0.002), and TCF3 was an independent risk factor of HCC. In vitro study exhibited that TCF3 knockdown dramatically suppressed cancer cell proliferation, and the underlying mechanism might be that the silencing of TCF3 reduced the expression of critical regulating proteins towards cell cycle and proteins involved in Wnt signaling pathways. CONCLUSIONS: TCF3 expression is significantly elevated in HCC and positively associated with the tumor size and TNM stage, as well as poor prognosis of HCC patients. The mechanism might be that TCF3 promotes cancer cell proliferation via activating Wnt signaling pathway.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fator 3 de Transcrição , Via de Sinalização Wnt , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Prognóstico , Fator 3 de Transcrição/genética , Fator 3 de Transcrição/metabolismo
17.
Transplantation ; 106(2): e126-e140, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34534191

RESUMO

BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) is an unavoidable outcome of liver transplantation, during which neutrophil extracellular traps (NETs) may play a critical role in the IRI-induced immune response to inflammation. The purpose of this study was to identify the function of recombinant human thrombomodulin (rTM) in the remission of hepatic IRI after liver transplantation and elucidate the specific mechanism. METHODS: NET formation (NETosis) was detected in the serum of liver transplantation patients and rats following liver transplantation. Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase 2´-deoxyuridine, 5´-triphosphate nick-end labeling staining, immunohistochemistry, and immunofluorescence were used to assess the effect of rTM on NETosis in vitro and in vivo. RESULTS: We found that rTM markedly inhibited neutrophil formation in NETs, reduced apoptosis in hepatocytes, alleviated rat hepatic IRI, and improved liver function. In vitro, rTM inhibited neutrophil formation in NETs, and lipopolysaccharide (a Toll-like receptor 4 agonist) reversed the inhibitory effect of rTM on NETosisN. rTM blocked a Toll-like receptor 4 and the downstream extracellular signal-regulated kinase/c-Jun NH2 terminal kinase and nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species/peptidylarginine deiminase 4 signaling pathways to protect against hepatic IRI and inhibit NETosis. In addition, we demonstrated that combined treatment with rTM and an NADPH oxidative inhibitor had a better effect than either treatment alone. CONCLUSIONS: NETs are a potential therapeutic target in hepatic IRI, and rTM could be used to prevent IR-induced hepatic injury. In addition, cotargeting NETosis-related signaling pathways might be a novel therapeutic strategy for hepatic IRI treatment.


Assuntos
Armadilhas Extracelulares , Transplante de Fígado , Traumatismo por Reperfusão , Animais , Humanos , Fígado/metabolismo , Transplante de Fígado/efeitos adversos , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Trombomodulina/metabolismo , Receptor 4 Toll-Like/metabolismo
18.
Surgery ; 171(6): 1596-1604, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34916072

RESUMO

BACKGROUND: The feasibility and safety of using longer ischemic interval during intermittent Pringle maneuver for hepatectomy in patients with hepatocellular carcinoma are still unclear. The aim of this study was to compare the short-term outcomes of hepatectomy using intermittent Pringle maneuver with an ischemic interval of 25 minutes versus 15 minutes in hepatocellular carcinoma patients. METHODS: A total of 344 patients with hepatocellular carcinoma undergoing hepatectomy were randomized to receive the intermittent Pringle maneuver with a 15-minute (n = 172) or 25-minute (n = 172) ischemic interval. Primary endpoint was transaminase-based postoperative hepatic injury, assessed by their peak values as well as area under the curve of the postoperative course of aminotransferases. Secondary endpoints included the intraoperative blood loss, transection speed, morbidity, mortality, and postoperative inflammatory reaction. RESULTS: There were no significant differences between the 2 groups in the postoperative aminotransferase serum levels or their area under the curve values, but the 25-minute intermittent Pringle maneuver group was associated with significantly higher speed for liver transection (1.38 vs 1.23 cm2/min, P = .002) and a lower blood loss during transection (109 vs 166 mL, P < .001) than the 15-minute intermittent Pringle maneuver group. Postoperative complications, inflammatory cytokines serum levels, and 90-day mortality were comparable. Stratification analysis showed that the 25-minute intermittent Pringle maneuver did not aggravate the hepatic injury but resulted in a lower blood loss during transection and higher transection speed in hepatocellular carcinoma patient undergoing laparoscopic or open hepatectomy. CONCLUSION: Intermittent Pringle maneuver with a 25-minute ischemic interval can be applied safely and efficiently in open or laparoscopic hepatectomy in patients with hepatocellular carcinoma patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Perda Sanguínea Cirúrgica/prevenção & controle , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos
19.
J Cancer Res Clin Oncol ; 147(2): 607-618, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32852635

RESUMO

BACKGROUND: How much difference there is between hepatic resection (HR) combined with intraoperative radiofrequency ablation (RFA) and living donor liver transplantation (LDLT) in treatment of multifocal hepatocellular carcinomas (HCCs) remains unclear. This study compared outcomes for patients with multifocal HCCs meeting the University of California San Francisco (UCSF) criteria treated by LDLT or HR + RFA. METHODS: A total of 126 consecutive Child-Pugh A patients with multifocal HCCs meeting the UCSF criteria, who underwent LDLT (n = 51) or HR + RFA (n = 75), were included. Propensity score (PS) matching was performed to adjust for baseline differences. Overall survival (OS) and recurrence-free survival (RFS) were calculated, and subgroup, multivariate and nomogram analyses were performed. RESULTS: LDLT provided significantly better OS and RFS than did HR + RFA before and after PS matching and reduced the dropout rate on waiting list, but HR + RFA was more convenient, less invasive and less cost. Patients with all lesions located in the same lobe had better OS and RFS than those located in the different lobes after HR + RFA. Multivariate and nomogram analyses revealed that HR + RFA, alpha-fetoprotein ≥ 400 ng/mL, the major tumour size > 3 cm and microvascular invasion were independent predictors of poor prognosis. CONCLUSION: For Child-Pugh A patients with multiple HCCs meeting the UCSF criteria, LDLT may offer significantly better long-term results than did HR + RFA, and HR + RFA may still be considered as an acceptable curative therapy for those without considering transplantation or as a bridge treatment for a patient, with a plan for transplantation in the future.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Doadores Vivos , Ablação por Radiofrequência , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nomogramas
20.
Transpl Int ; 35: 10177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35185367

RESUMO

There are two causes of graft compression in the large-for-size syndrome (LFSS). One is a shortage of intra-abdominal space for the liver graft, and the other is the size discrepancy between the anteroposterior dimensions of the liver graft and the lower right hemithorax of the recipient. The former could be treated using delayed fascial closure or mesh closure, but the latter may only be treated by reduction of the right liver graft to increase space. Given that split liver transplantation has strict requirements regarding donor and recipient selections, reduced-size liver transplantation, in most cases, may be the only solution. However, surgical strategies for the reduction of the right liver graft for adult liver transplantations are relatively unfamiliar. Herein, we introduce a novel strategy of HuaXi-ex vivo right posterior sectionectomy while preserving the right hepatic vein in the graft to prevent LFSS and propose its initial indications.


Assuntos
Transplante de Fígado , Adulto , Veias Hepáticas , Humanos , Fígado , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doadores Vivos , Projetos Piloto , Doadores de Tecidos
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