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Background: The associations between platelet-to-lymphocyte ratio (PLR) and non-alcoholic fatty liver disease (NAFLD) and cirrhosis are unclear, and there are still no effective means for diagnosing or monitoring disease progression. Methods: Data from the National Health and Nutrition Examination Surveys were collected for analysis. Logistic regression and restricted cubic splines were used to evaluate the associations between PLR and NAFLD and cirrhosis in different populations. The Area Under Curve Receiver Operating Characteristic (AUCROC) was used to distinguish the models. Threshold analysis was performed by constructing a two-piecewise linear regression. Correlation analysis was performed separately on either side of the inflection point. Results: A total of 5724 adults were included. Logistic regression analysis revealed that the PLR was associated with NAFLD and cirrhosis (AUCROC of NAFLD: 0.803; AUCROC of cirrhosis: 0.851). The AUCROC of the PLR for predicting NAFLD incidence was 0.762 in the diabetic population and 0.804 in the nondiabetic population. High PLR predicted cirrhosis in the diabetic population, with an AUCROC of 0.824, whereas a high PLR was not associated with cirrhosis in the nondiabetic population. The restricted cubic spline revealed a negative linear correlation between the PLR and NAFLD incidence. The inflection point of the PLR for NAFLD was 180.74. A PLR ≤180.74 was statistically significant (odds ratio=0.997, 95% confidence interval=0.995-0.999). In the NAFLD population, the PLR was negatively correlated with cirrhosis at a PLR ≤130.5 (odds ratio=0.987, 95% confidence interval=0.977-0.996) and positively correlated with cirrhosis at a PLR > 130.5 (odds ratio=1.006, 95% confidence interval=1.001-1.012). Conclusions: The PLR and NAFLD were negatively correlated in the U.S. population. The PLR had a U-shaped relationship with cirrhosis in the NAFLD population. The PLR has potential value in monitoring NAFLD patient progression to cirrhosis.
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Plaquetas , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Masculino , Femenino , Cirrosis Hepática/sangre , Cirrosis Hepática/epidemiología , Persona de Mediana Edad , Estudios Transversales , Adulto , Plaquetas/patología , Linfocitos , Recuento de Plaquetas , Recuento de Linfocitos , Encuestas Nutricionales , Factores de Riesgo , Anciano , Valor Predictivo de las PruebasRESUMEN
Leg weakness is a prevalent health condition in pig farms. The augmentation of cannon bone circumference and bone mineral density can effectively improve limb strength in pigs and alleviate leg weakness. This study measured forelimb cannon bone circumference (fCBC) and rear limb cannon bone circumference (rCBC) using an inelastic tapeline and rear limb metatarsal area bone mineral density (raBMD) using a dual-energy X-ray absorptiometry bone density scanner. The samples of Yorkshire castrated boars were genotyped using a 50K single-nucleotide polymorphism (SNP) array. The SNP-chip data were imputed to the level of whole-genome sequencing data (iWGS). This study used iWGS data to perform genome-wide association studies and identified novel significant SNPs associated with fCBC on SSC6, SSC12, and SSC13, rCBC on SSC12 and SSC14, and raBMD on SSC7. Based on the high phenotypic and genetic correlations between CBC and raBMD, multi-trait meta-analysis was performed to identify pleiotropic SNPs. A significant potential pleiotropic quantitative trait locus (QTL) regulating both CBC and raBMD was identified on SSC15. Bayes fine mapping was used to establish the confidence intervals for these novel QTLs with the most refined confidence interval narrowed down to 56 kb (15.11 to 15.17 Mb on SSC12 for fCBC). Furthermore, the confidence interval for the potential pleiotropic QTL on SSC15 in the meta-analysis was narrowed down to 7.45 kb (137.55 to137.56 Mb on SSC15). Based on the biological functions of genes, the following genes were identified as novel regulatory candidates for different phenotypes: DDX42, MYSM1, FTSJ3, and MECOM for fCBC; SMURF2, and STC1 for rCBC; RGMA for raBMD. Additionally, RAMP1, which was determined to be located 23.68 kb upstream of the confidence interval of the QTL on SSC15 in the meta-analysis, was identified as a potential pleiotropic candidate gene regulating both CBC and raBMD. These findings offered valuable insights for identifying pathogenic genes and elucidating the genetic mechanisms underlying CBC and BMD.
Leg weakness, a highly prevalent health condition in pig breeding farms, adversely affects the lifespan of breeding pigs. The augmentation of cannon bone circumference (CBC) and bone mineral density (BMD), which are objective measures of limb strength in pigs, can effectively alleviate leg weakness. To identify candidate genes regulating CBC and BMD in pigs, this study performed single-trait genome-wide association studies and multi-trait meta-analysis on all individuals with phenotype data. Additionally, the confidence intervals of quantitative trait locus (QTL) were determined using Bayesian methods. Four CBC-associated QTLs and one BMD-associated QTL were identified. Additionally, one potential pleiotropic QTL associated with both CBC and rear limb metatarsal area BMD (raBMD) was identified. This study demonstrated that DDX42, MYSM1, FTSJ3, and MECOM were candidate genes regulating forelimb CBC, while SMURF2 and STC1 were candidate genes regulating rear limb CBC. Additionally, RGMA was demonstrated to regulate raBMD, while RAMP1 was identified as a potential pleiotropic gene regulating both CBC and raBMD. The findings of this study provide valuable insights into the genetic mechanisms underlying limb growth and bone mineral accumulation.
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Densidad Ósea , Estudio de Asociación del Genoma Completo , Porcinos/genética , Masculino , Animales , Densidad Ósea/genética , Estudio de Asociación del Genoma Completo/veterinaria , Teorema de Bayes , Pleiotropía Genética , Sitios de Carácter Cuantitativo , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
Mammalian oocyte maturation relies on mitochondrial ATP production, but this can lead to damaging reactive oxygen species (ROS). SIRT3, a mitochondrial sirtuin, plays a critical role in regulating mitochondrial redox balance in mouse oocytes under stress; however, its specific roles in porcine oocytes remain unclear. In this study, we utilized the SIRT3 inhibitor 3-TYP to investigate SIRT3's importance in porcine oocyte maturation. Our findings revealed that SIRT3 is expressed in porcine oocytes and its inhibition leads to maturation failure. This was evident through reduced polar body extrusion, arrested cell cycle, as well as disrupted spindle organization and actin distribution. Furthermore, SIRT3 inhibition resulted in a decrease in mitochondrial DNA copy numbers, disruption of mitochondrial membrane potential, and reduced ATP levels, all indicating impaired mitochondrial function in porcine oocytes. Additionally, the primary source of damaged mitochondria was associated with decreased levels of deacetylated superoxide dismutase 2 (SOD2) after SIRT3 inhibition, which led to ROS accumulation and oxidative stress-induced apoptosis. Taken together, our results suggest that SIRT3 regulates the levels of deacetylated SOD2 to maintain redox balance and preserve mitochondrial function during porcine oocyte maturation, with potential implications for improving pig reproduction.
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Enfermedades Mitocondriales , Sirtuina 3 , Ratones , Animales , Porcinos , Especies Reactivas de Oxígeno , Sirtuina 3/genética , Sirtuina 3/metabolismo , Estrés Oxidativo , Oocitos/metabolismo , Adenosina Trifosfato/metabolismo , Enfermedades Mitocondriales/metabolismo , Mamíferos/metabolismoRESUMEN
BACKGROUND: The study aimed to evaluate the prognostic impact of circulating tumor cells (CTCs) in patients with gallbladder adenocarcinoma after resection. MATERIALS AND METHODS: Between January 2018 and January 2021, 101 consecutive patients with gallbladder adenocarcinoma were included. CTCs were detected and enumerated using the CanPatrol® technique. The follow-up period ended in January 2023. The cancer-specific survival (CSS) and disease-free survival (DFS) were calculated using log-rank and Cox regression analyses. RESULTS: CTCs were detected positively in 61.54% (8/13) of the patients in the non-operation group and 13.64% (12/88) in the operation group. In the operation group, the median CSS for CTCs-positive and CTCs-negative patients was 5.0 and 9.5 months (P < 0.001), respectively, and DFS was 2.8 and 5.0 months at stage III (P < 0.001), respectively. In the non-operation group, the median CSS for CTCs-positive and CTCs-negative patients was 3.5 and 6.5 months (P = 0.0031), respectively. The median CSS for CTCs-positive patients in the operation group was similar to that in the non-operation group (P = 0.67). Multivariate analyses showed that positive CTCs was an independent risk factor for poor CSS (HR 0.066, 95% CI 0.021-0.206, P < 0.001) as well as lymph infiltration (HR 0.320, 95% CI 0.110-0.930, P = 0.036), without R0 curative resection (HR 7.520, 95% CI 2.100-26.931, P = 0.002), and without adjuvant chemotherapy (HR 7.730, 95% CI 2.416-24.731, P < 0.001). CONCLUSION: Positive CTCs was an independent predictor of poor prognosis after resection in patients with gallbladder adenocarcinoma. Preoperative detection of CTCs may play an important guiding role in formulating treatment strategies for these patients.
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Adenocarcinoma , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patología , Vesícula Biliar/patología , Pronóstico , Adenocarcinoma/cirugía , Factores de RiesgoRESUMEN
Background Hepatocellular carcinomas (HCCs) can be divided into proliferative and nonproliferative types, which may have implications for outcomes after conventional transarterial chemoembolization (cTACE). Biopsy to identify proliferative HCC is not routinely performed before cTACE. Purpose To develop and validate a predictive model for identifying proliferative HCCs using CT imaging features and to compare therapeutic outcomes between predicted proliferative and nonproliferative HCCs after cTACE according to this model. Materials and Methods This retrospective multicenter study included adults with HCC who underwent liver resection or cTACE between August 2013 and December 2020. A CT-based predictive model for identifying proliferative HCCs was developed and externally validated in a cohort that underwent resection. Diagnostic performance was calculated for the model. Thereafter, patients in the cTACE cohort were stratified into groups with predicted proliferative or nonproliferative HCCs according to the model. The primary outcome was overall survival (OS), and the secondary outcomes were tumor response rate and progression-free survival (PFS). These were compared between the two groups with use of the χ2 test and the log-rank test. Results A total of 1194 patients (1021 men; mean age, 54 years ± 12 [SD]; median follow-up time, 29.1 months) were included. The predictive model, named the SMARS score, incorporated lobulated shape, mosaic architecture, α-fetoprotein levels, rim arterial phase hyperenhancement, and satellite lesions. The area under the receiver operating characteristic curve for the SMARS score was 0.83 for the training cohort and 0.80 for the validation cohort. According to the SMARS score, patients with predicted proliferative HCCs (n = 114) had lower tumor response rate (48% vs 71%; P < .001) and worse PFS (6.6 months vs 12.4 months; P < .001) and OS (14.4 months vs 38.7 months; P < .001) than those with nonproliferative HCCs (n = 263). Conclusion The predictive model demonstrated good performance for identifying proliferative HCCs. According to the SMARS score, patients with predicted proliferative HCCs have worse prognosis than those with predicted nonproliferative HCCs after cTACE. © RSNA, 2023 Supplemental material is available for this article.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Adulto , Masculino , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Supervivencia sin Progresión , Tomografía Computarizada por Rayos XRESUMEN
Background: Neointimal hyperplasia (NH) is a crucial pathophysiological feature in vascular transplant and in-stent restenosis. Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in neointimal hyperplasia. This study aims to explore the potentialities and mechanism of sulfasalazine (SSZ) in the prevention of restenosis. Methods: Sulfasalazine was encapsulated in nanoparticles made of poly (lactic-co-glycolic acid) (PLGA). In vivo, carotid ligation injury was induced in mice to induce Neointimal hyperplasia, with or without sulfasalazine containing nanoparticles (NP-SSZ) treatment. After 4 weeks, the arteries were collected for histology, immunofluorescence, Western blotting (WB) and qRT-PCR. In vitro, vascular smooth muscle cells were treated with TNF-α to induce cell proliferation and migration, followed by SSZ or vehicle treatment. WB was performed to further explore its mechanism. Results: The ratio of intima to media thickness (I/M) was increased after ligation injury on day 28, while the ratio was significantly reduced in the NP-SSZ treatment group. The dual positive nuclei of Ki-67 and α-SMA were 47.83% ± 9.15%, whereas only 29.83% ± 5.98% in the NP-SSZ-treated group (p < 0.05). Both MMP-2 and MMP-9 were decreased in the NP-SSZ treatment group (p < 0.05, p < 0.05, respectively) compared to the control group. The levels of the targeted inflammatory genes (TNF-α, VCAM-1, ICAM-1, MCP-1) were lower in the NP-SSZ treatment group compared with the control group. In vitro, the proliferating cell nuclear antigen (PCNA) expression was significantly decreased in the SSZ treatment group. The cell viability of VSMCs was markedly increased in the TNF-α treatment group, whereas sulfasalazine treatment inhibited this effect. LC3 II and P62 protein expression were higher in the SSZ group than in the vehicle group both in vitro and in vivo. The phosphorylation of NF-kB (p-NF-kB) and the phosphorylation of mTOR (p-mTOR) were decreased in the TNF-α+ SSZ group, whereas the P62 and LC3 II expression levels were increased. However, the expression level of p-mTOR, P62, and LC3 II was reversed after co-treatment with the agonist of mTOR MHY1485, whereas the p-NF-kB expression level was unchanged. Conclusion: sulfasalazine inhibited vascular smooth muscle cells proliferation and migration in vitro and Neointimal hyperplasia in vivo through NF-kB/mTOR-mediated autophagy.
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BACKGROUND: Several scoring systems are currently used to predict prognosis of hepatocellular carcinoma (HCC), but none of them integrates liver function, systemic inflammation, and tumor characteristics in a unified model. The current study aimed to develop and validate a novel prognostic score that integrates liver function, systemic inflammation, and tumor characteristics in a unified model to predict the prognosis of HCC after curative resection. METHODS: Patients with HCC who underwent curative liver resection were included in a training set (n = 1027). Multivariate Cox regression was performed to determine the risk factors for a poor prognosis. A prognostic score was developed by assigning points for risk factors in proportion to beta coefficients in a Cox multivariable model. Predictive performance and distinction ability of the prognostic score were further evaluated in two independent validation cohorts treated with either curative resection (n = 281) or transarterial chemoembolization (TACE) (n = 404) and compared with 16 other models. RESULTS: The prognostic predictive system, named the function-inflammation-burden-alpha-fetoprotein (FIBA) score, was derived by assigning points for six independent predictors including albumin, total bilirubin, lymphocyte count, diameter of the largest tumor, number of tumors, and alpha-fetoprotein (AFP). The FIBA score showed an outperformed predictive value compared with other systems in both training and validation cohorts by giving the highest C-index, likelihood ratio chi-square values, and Wald test values as well as the lowest Akaike information criterion. CONCLUSION: The FIBA score can be used to stratify HCC patients treated with curative resection. Meanwhile, the FIBA score performs well against other prognostic scoring systems and is potentially broadly applicable to a TACE-treated patient cohort.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , alfa-Fetoproteínas , Pronóstico , Inflamación , Estudios RetrospectivosRESUMEN
Colorectal cancer (CRC) is one of the major killer diseases worldwide, and more effective therapeutic compounds for CRC treatment are urgently needed. Although bioactive natural products derived from endophytic fungi have been extensively employed as antibiotics and anticancer agents, little is known about the effect of Rhytidhysteron sp. BZM-9 (an endophytic fungus)-derived compounds on CRC. Herein, a natural molecule porric acid E was isolated from Rhytidhysteron sp. BZM-9. Alamar Blue cell viability assay, Western blotting, transmission electron microscopy, flow cytometry analysis, and fluorescence image examination were employed to evaluate the antitumor effects of porric acid E on CRC cell lines. To establish the xenograft tumor model, nude mice received subcutaneous implants consisting of CRC cells on their flanks. Then the mice were treated with porric acid E or vehicle to assess the tumor-killing effects. The results revealed that porric acid E exhibited cytotoxicity by inhibiting proliferation and promoting apoptosis in CRC cells in vitro. Additionally, compared with fluorouracil (5-FU), porric acid E exhibited a more potent inhibitory effect on CRC HT29 cells. Importantly, extensive autophagy induced by porric acid E was detected in CRC cells, whereas inhibition of autophagy could significantly ameliorate porric acid E-mediated cytotoxic effect on CRC cells. Moreover, porric acid E treatment could markedly suppress subcutaneous HT29 xenograft tumor growth in vivo. Bioinformatics prediction indicated that Beclin-1 might be the potential target of porric acid E. These findings might afford a useful and important method for the treatment of CRC through fungal endophyte-derived natural compounds.
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Background: Both the Barcelona Clinic Liver Cancer (BCLC) staging and the Hong Kong Liver Cancer (HKLC) staging have their own definitions of ideal patients for liver resection (IPLR) in hepatocellular carcinoma (HCC). This study aimed to compare the prognosis of IPLRs between the BCLC and HKLC staging systems, and to identify patients who may benefit from liver resection (LR) in the HKLC staging but beyond the BCLC staging. Methods: This retrospective study evaluated 1,296 consecutive patients with HCC who underwent LR between August 2013 and April 2021 (457 patients and 1,046 patients were IPLR according to the BCLC and HKLC staging systems, respectively). Overall survival (OS) was compared between the two groups. To assess potential benefit of LR for IPLR in the HKLC staging but beyond the BCLC staging, univariate and multivariate Cox regression analysis was performed to determine prognostic factors of OS, and prognostic stratification was performed based on the selected prognostic factors. The IPLRs in the HKLC staging but beyond the BCLC staging were divided into subgroups according to the prognostic stratification and separately compared with the IPLRs in the BCLC staging. Results: OS was different between the two staging systems (P = 0.011). All the 457 IPLRs in the BCLC staging were also the IPLRs in the HKLC staging. Diameter of the largest tumor5 cm (HR = 1.58; 95% CI: 1.18-2.10; P = 0.002) and liver cirrhosis (HR = 1.61; 95% CI: 1.19-2.20; P = 0.002) were risk factors for poor OS in IPLRs in the HKLC staging but beyond the BCLC staging; hence, patients were divided into the low-risk (n = 104), intermediate-risk (n = 369), and high-risk groups (n = 116) accordingly. There was no difference in OS between patients in the BCLC staging and patients in low-risk group (P = 0.996). However, OS was significantly different between patients in the BCLC staging and those in intermediate-risk (P = 0.003) and high-risk groups (P < 0.001). Conclusion: IPLRs in the BCLC staging system have better prognosis. However, IPLRs in the HKLC staging system but beyond the BCLC staging may have equivalent prognosis to IPLRs in the BCLC staging if the tumor size is ≤ 5 cm and liver cirrhosis is absent.
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BACKGROUND: Liver resection (LRE) and microwave ablation (MWA) for hepatocellular carcinoma (HCC) have been widely compared. AIMS: To compare the therapeutic outcomes of percutaneous MWA and LRE for HCC in ideal candidates for ablation according to Barcelona Clinic Liver Cancer (BCLC) staging METHODS: Between August 2013 and November 2020, 483 consecutive patients meeting criteria for "ideal candidates for ablation" per the BCLC staging initially treated with MWA (n = 168) or LRE (n = 315) were included. Patients were further divided into BCLC-0 (n = 116) and BCLC-A (n = 367) groups. Overall survival (OS), recurrence-free survival (RFS) and post-procedure-related complication rates were compared before and after propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) in the overall population and subgroups. Multivariate Cox regression analysis was performed to determine whether the treatment modality was an independent prognostic factor. RESULTS: LRE had a better RFS and similar OS and post-procedure-related complication rates compared to MWA in the overall population and in the BCLC-A subgroup both before and after PSM and IPTW. However, the OS, RFS and post-procedure-related complication rates were equivalent between the two groups before and after PSM and IPTW in patients with BCLC-0 disease. The multivariate Cox regression analysis showed that LRE was associated with better RFS over MWA in overall population (p = 0.003; HR = 0.67; 95% CI: 0.51-0.87) and BCLC-A disease (p = 0.046; HR = 0.74; 95% CI: 0.56-0.99), while it did not differ in OS. CONCLUSION: An 'ideal candidate for ablation' according to the BCLC staging system may not be an ideal candidate for MWA. However, patients with BCLC-0 may be the optimal population for MWA.
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Carcinoma Hepatocelular , Ablación por Catéter , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Puntaje de Propensión , Microondas/uso terapéutico , Estadificación de Neoplasias , Ablación por Catéter/efectos adversos , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Cholangiocarcinoma (CCA) leads to poor prognosis due to high aggressiveness and common chemoresistance. Dihydromyricetin (DMY), the main bioactive compound isolated from Ampelopsis grossedentata, exhibits broad anti-tumor effects. This study aimed to investigate the inhibitory effect of DMY on CCA tumor growth and epithelial-mesenchymal transition (EMT) and its underlying mechanism in CCA. DMY treatment significantly inhibited cell proliferation and EMT in CCA cell lines. The expression of ZEB1 and vimentin were down-regulated, while the level of E-cadherin was increased after DMY treatment. By analyzing the TCGA dataset, we found that miR-455 expression was significantly downregulated, while the level of ZEB1 was up-regulated in human CCA tumor tissues compared to normal samples. Mechanistic studies showed that ZEB1 was a direct target of miR-455-3p in CCA. Moreover, DMY treatment potently increased miR-455-3p expression and inhibited ZEB1 expression. Inhibition of miR-455-3p expression abolished DMY's inhibitory effects on tumor growth and EMT in both CCA cells and cell-engrafted nude mice. Finally, DMY significantly suppressed the expressions of p-PI3K and p-AKT, while silencing miR-455-3p remarkably abrogated the inhibitory effect. In conclusion, DMY suppresses tumor growth and EMT through regulating miR-455-3p in human cholangiocarcinoma, suggesting a potential option for CCA treatment.
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Citrinin (CTN) is a mycotoxin, which is isolated from Penicillium citrinum and widely existed in the contaminated feeds. It is reported that CTN is toxic to heart, liver, and reproductive system. Previous studies indicated that CTN induced apoptosis in oocytes and embryos. In this study, we reported the potential causes of CTN on embryo development. Our results showed that 40 µM CTN exposure significantly reduced the first cleavage of mouse embryos, showing with the low rate of 2-cell embryos. We found that CTN induced DNA damage, showing the higher positive γH2A.X signals. Autophagy was occurred since more LC3 positive autophagosomes were found in the cytoplasm. This could be confirmed by the enhanced lysosome function, since higher accumulated lysosome distribution were found and LAMP2 was also increased under CTN exposure. Besides, we showed that mitochondria distribution was disturbed, indicating that CTN could disrupt mitochondria function, which could be the possible reason for the oxidative stress and apoptosis in CTN-exposed embryos. In conclusion, our study showed that CTN exposure had adverse effects on the early embryo development during first cleavage through its effects on the induction of DNA damage, autophagy, and mitochondria dysfunction.
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Citrinina , Animales , Apoptosis , Autofagia , Citrinina/toxicidad , Daño del ADN , Ratones , Mitocondrias , PenicilliumRESUMEN
The p53-upregulated modulator of apoptosis (PUMA) has been reported to be involved in various types of cancer. However, its potential biological role in gallbladder carcinoma (GBC) has not been fully elucidated. The present study aimed to determine the expression levels of PUMA and its biological effects on GBC. The mRNA and protein expression levels of PUMA in GBC tissues and cell lines were measured using reverse transcription-quantitative PCR and western blotting, respectively. The effects of PUMA overexpression on cell viability, proliferation and invasive ability were determined in vitro using the MTT, colony formation and Transwell invasion assays, respectively. The apoptotic rates were detected using the Annexin V-FITC apoptosis detection kit. Furthermore, follow-up of patients with GBC was performed to identify the association between PUMA expression levels and GBC prognosis. The results of the present study demonstrated that the expression levels of PUMA were significantly lower in the GBC tissues and cell lines compared with those in adjacent normal gallbladder tissues and normal gallbladder cells, respectively. Further experiments indicated that overexpression of PUMA inhibited the viability, proliferation and invasive ability of GBC cells compared with those in the control-transfected GBC cells. In addition, overexpression of PUMA significantly promoted apoptosis in GBC cells. Furthermore, overexpression of PUMA inhibited epithelial-mesenchymal transition, and promoted Bax upregulation and Bcl-2 downregulation compared with those in the control group. Low PUMA expression levels were associated with a short overall survival time in patients with GBC. In conclusions, PUMA may act as a tumor suppressor in GBC and may serve as a potential novel treatment target for human GBC.
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BACKGROUND: Advanced gastric cancer (aGC) has a high global incidence and a high mortality rate and because of its high malignancy and heterogeneity, the existing methods for prognosis are limited, and a new treatment model is necessary. Circulating tumor cells (CTCs) could be considered as a "liquid biopsy" for tumor diagnosis and for monitoring treatment responses and predicting clinical outcome. Clinical studies support the efficacy of programmed cell death 1 (PD-1) immunotherapy in a subset of aGC. METHODS: Cell capture efficiency, as described by the CanPatrol CTC enrichment technique, was validated using artificial blood samples as well as blood samples from 32 aGC patients. Clinicopathologic data of patients were collected from the hospital information system. We used CanPatrol for CTC isolation, classification, and clinical analysis. RESULTS: A cell capture efficiency of >80% was achieved. Significant correlation was observed between CTC enumeration and clinicopathology parameters, including the Lauren classification (r=0.470, P=0.008), perineural invasion (r=0.393, P=0.029), TNM stage (r=0.740, P<0.001), and Ki-67 level (r=0.510, P=0.005). When compared to the traditional methods, monitoring CTC subtypes exhibits higher sensitivity of evaluating the disease status. Enumeration of epithelial CTC subset and its relative abundance in the total CTC pool are highly correlated with clinical efficacy. CTC programmed cell death ligand-1 (PD-L1) could be successfully detected for immunotherapy in addition to PD-L1 immunohistochemistry and microsatellite instability. CONCLUSION: We provide a new method that allows for the simple and effective detection of CTCs in aGC. It has potential clinical applications in monitoring prognosis and guiding future individualized immunotherapy.
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BACKGROUND: The purpose of this study is to compare the clinical outcomes of laparoscopic liver resection versus open liver resection for recurrent hepatocellular carcinoma (RHCC). METHODS: Published studies which investigated laparoscopic versus open liver resection for RHCC were identified, and meta-analysis was used for statistical analysis. RESULTS: Six studies were analyzed by meta-analysis method, and cumulative 335 cases were included in this study. Laparoscopic liver resection was performed in 145 cases, and open liver resection was performed in 190 cases. Meta-analysis showed that there was no difference in operative time and 90-day mortality between the laparoscopic group and the open group (p = 0.06 and p = 0.06 respectively); Nevertheless, compared with the open group, the laparoscopic group resulted in significantly lower rate of in-hospital complication (p < 0.0001), much less blood loss (p < 0.0001) and shorter postoperative hospital stay (p = 0.002). CONCLUSION: Laparoscopic liver resection for RHCC offers a benefit of lower in-hospital complication rate, less blood loss, shorter postoperative hospital stay, while similar operative time and 90-day mortality as the open liver resection. Laparoscopic liver resection is feasible with satisfactory postoperative outcomes and can be a safe alternative treatment strategy to open procedure for RHCC.
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Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Hepatectomía/métodos , Humanos , Laparoscopía/métodos , Tiempo de Internación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Técnicas de Abdomen Abierto/métodos , Tempo Operativo , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the early and midterm outcomes of endovascular repair of Stanford type B aortic dissection (TBAD) with an aberrant right subclavian artery (ARSA). MATERIALS AND METHODS: From November 2012 to July 2018, 15 patients (13 male, 2 female) who had TBAD with ARSA underwent total endovascular repair, including thoracic endovascular aortic repair (TEVAR), left subclavian artery (LSA) chimney technique, LSA fenestration technique, and double chimney technique (LSA chimney and ARSA periscope). The mean age was 55 years. Kommerell diverticulum (KD) occurred in 2 patients, which were covered by means of oversized aortic stents. All patients had preoperative imaging examinations for assessing cerebral blood flow and the dominant vertebral arteries. RESULTS: All procedures were completed successfully. There was no in-hospital mortality. The mean procedural time was 98 ± 40 minutes (range 50-190). The mean preoperative diameters of the maximum descending aorta, false lumen, and true lumen in the descending aorta versus postoperative were 37 ± 10 mm (range 28-67), 18 ± 9 mm (range 9-41), and 19 ± 6 mm (range 10-35) versus 34 ± 9 mm (range 25-64), 5 ± 8 mm (range 0-28), and 28 ± 5 mm (range 19-37), respectively. Right upper extremity weakness was observed in 2 patients, which recovered gradually during follow-up. Immediate type Ia endoleak was detected in 1 patient. The mean follow-up time was 33 ± 20 months. During follow-up, no ARSA steal syndrome, spinal cord ischemia, or strokes were not observed. CONCLUSIONS: Endovascular treatment for TBAD with ARSA was feasible and safe with a satisfactory midterm follow-up outcome.
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Aneurisma de la Aorta/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular , Anomalías Cardiovasculares/cirugía , Procedimientos Endovasculares , Arteria Subclavia/anomalías , Adulto , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/mortalidad , Disección Aórtica/fisiopatología , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/mortalidad , Aneurisma de la Aorta/fisiopatología , Prótesis Vascular , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/mortalidad , Anomalías Cardiovasculares/diagnóstico por imagen , Anomalías Cardiovasculares/mortalidad , Anomalías Cardiovasculares/fisiopatología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/etiología , Diseño de Prótesis , Estudios Retrospectivos , Factores de Riesgo , Stents , Arteria Subclavia/diagnóstico por imagen , Arteria Subclavia/fisiopatología , Arteria Subclavia/cirugía , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Quadratus lumborum (QL) block is increasingly being used as a new abdominal nerve block technique. In some studies of mid and lower abdominal and hip analgesia, continuous QL block achieved favorable outcomes as an alternative to continuous intravenous analgesia with opioids. However, the use of continuous QL block for upper abdominal pain is less well characterized. This study aimed to investigate the effects of continuous anterior QL block (CQLB) on postoperative pain and recovery in patients undergoing open liver resection. METHODS: Sixty-three patients underwent elective open liver resection were randomly divided into continuous anterior QL block (CQLB, n = 32) group and patient-controlled intravenous analgesia (PCIA, n = 31) group. Patients in CQLB group underwent ultrasound-guided anterior QL block at the second lumbar vertebral transverse processes before general anesthesia, followed by postoperative CQLB analgesia. Patients in PCIA group underwent continuous intravenous analgesia postoperatively. Postoperative numerical rating scale (NRS) pain scores upon coughing and at rest, self-administered analgesic counts, rate of rescue analgesic use, time to first out-of-bed activity and anal flatus after surgery, and incidences of analgesic-related adverse effects were recorded. RESULTS: Postoperative NRS pain scores on coughing in CQLB group at different time points and NRS pain score at rest 48 h after surgery were significantly lower than those in PCIA group (P < 0.05). Time to first out-of-bed activity and anal flatus after surgery in CQLB group were significantly earlier than those in PCIA group (P < 0.05). No significant differences of postoperative self-administered analgesic counts, rate of postoperative rescue analgesic usage, or incidences of analgesic-related adverse effects were found between the two groups (P > 0.05). CONCLUSIONS: Ultrasound-guided anterior QL block significantly alleviated the pain during coughing after surgery, shortened the time to first out-of-bed activity and anal flatus, promoting postoperative recovery of the patients undergoing open liver resection. TRIAL REGISTRATION: This study has been registered in April 1, 2018 on Chinese Clinical Trail Registry, the registration number is ChiCTR1800015454 .
Asunto(s)
Analgesia Controlada por el Paciente/métodos , Hepatectomía/métodos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Adulto , Analgésicos/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND: We introduce the "kissing stent-grafts technique" for a patient who suffered from a pseudoaneurysm in bifurcation of innominate artery. This technique repaired an innominate artery bifurcation pseudoaneurysm; it successfully isolated the pseudoaneurysm and preserved both right subclavian and right common carotid artery. CASE PRESENTATION: A 60-year-old Asian (Chinese) woman complained of discovering a cervical pulsatile mass. A pseudoaneurysm at the location of innominate artery bifurcation is a rare and difficult situation that should be treated by vascular surgeons. To our knowledge, this is the first case to use the "kissing stent-grafts technique" in treating innominate bifurcation pseudoaneurysm. With this minimally invasive endovascular treatment, our patient avoided open surgery and recovered quickly. CONCLUSIONS: When treating vascular lesions with complicated anatomy, endovascular treatment always has the merit of being minimally invasive. "Kissing stent-grafts technique" can be useful in locations other than coronary and aortic bifurcation.
Asunto(s)
Aneurisma Falso/cirugía , Arteriopatías Oclusivas/cirugía , Tronco Braquiocefálico/cirugía , Arteria Carótida Común/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Stents , Aneurisma Falso/etiología , Aneurisma Falso/fisiopatología , Arteriopatías Oclusivas/fisiopatología , Tronco Braquiocefálico/fisiopatología , Arteria Carótida Común/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with Stanford B aortic dissection (AD) are usually found to have sleep apnea syndrome (SAS). This condition always complicates the patients' respiration. In this study, we collected and analyzed data of patients' perioperative managements during thoracic endovascular aortic repair (TEVAR) for treating patients with Stanford B AD and SAS. Comparison has been made between the patients with SAS and those without SAS. METHODS: Between June 2013 and June 2014, the clinical data and outcomes of the Stanford B AD patients in the Department of Vascular Surgery in the Second Xiangya Hospital were retrospectively reviewed and studied. According to the result of polysomnography obtained by using a portable polysomnography monitor (Nox T3, Nox Medical Co. Iceland) in TEVAR candidates, patients have been stratified into SAS-positive and SAS-negative group. Comparison of various variables has been made between these 2 groups. RESULTS: One hundred thirty-four patients, with Stanford B AD and treated by TEVAR in our center, were enrolled in this study. Patients' mean age was 52.46 ± 10.84 years. Gender ratio is 114:20, including male 85.07% (114/134) and female 14.93% (20/134). TEVAR was performed in 71.64% (96/134) patients under general anesthesia and 38 patients under local anesthesia. The mean body mass index (BMI) was 23.5 ± 4.2, and the longest follow-up time was 46 months. The patients were stratified into SAS-positive group (n = 23) and SAS-negative group (n = 111). Compared with the patients in the SAS-negative group, those in the SAS-positive group were younger (54.36 ± 0.97 vs. 43.3 ± 1.84 P < 0.0001) but had higher BMI (25.48 ± 0.71 vs. 22.24 ± 0.23, P < 0.0001), with longer hospitalization time (25.52 ± 0.59 vs. 15.68 ± 0.27; P < 0.0001) and without significant differences in the intensive care unit (ICU) stay time (54.87 ± 12.57 vs. 40.27 ± 8.10; P = 0.3369). Furthermore, the complication rate of pulmonary infection (65.22% vs. 13.51%; P < 0.0001), respiratory failure (26.09% vs. 1.80%; P = 0.003), heart failure (26.09% vs. 3.60%; P = 0.0018), and renal failure (30.43% vs. 5.40%; P = 0.0016) are significantly different between SAS-positive and SAS-negative groups. According to the 46-month follow-up, the survival rate of the 2 groups had no significant differences (P = 0.0846). The SAS-negative group result showed that the survival time had no significant correlation with all the factors we explored, whereas the SAS-positive group result showed that the survival time is significantly correlated only with pulmonary infection/failure (r = 0.2798, 95% confidence interval 0.08741 to 0.452, P = 0.0038). CONCLUSIONS: Stanford B AD patients who had SAS are likely to have higher BMI. After treating with TEVAR, they usually have longer hospitalization and ICU stay time, as well as higher complication rate. However, there are no significant differences of the survival rate in midtime follow-up. The respiratory system evaluation should be considered carefully in those patients who have diagnosed as having SAS before and after TEVAR because those patients' survival situation may have correlation with their respiratory condition.