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INTRODUCTION: Pancreaticojejunostomy have been studied and modified for more than a hundred years. We investigated a new method of pancreaticojejunostomy to explore its value in laparoscopic pancreaticoduodenectomy. PATIENTS AND METHODS: A retrospective analysis was conducted on the clinical data of 93 patients who underwent laparoscopic pancreaticoduodenectomy with 'Shunt-block combined' pancreaticojejunostomy at Ningbo Medical Center Lihuili Hospital from April 2017 to February 2023. RESULTS: All patients successfully completed the surgery, with two cases requiring conversion to open surgery. The average operation time was 328.5 (180-532) min, the average intraoperative blood loss was 182.9 (50-1000) mL and the average laparoscopic pancreaticojejunostomy time was 29.6 (20-39) min. There were no cases of grade C pancreatic fistula postoperatively, 10 cases of grade B pancreatic fistula, 43 cases of biochemical fistula and 40 cases without detected pancreatic fistula. CONCLUSION: 'Shunt-block combined' pancreaticojejunostomy was a safe and effective method for pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.
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Formin proteins catalyze actin nucleation and microfilament polymerization. Inverted formin 2 (INF2) is an atypical diaphanous-related formin characterized by polymerization and depolymerization of actin. Accumulating evidence showed that INF2 is associated with kidney disease focal segmental glomerulosclerosis and cancers, such as colorectal and thyroid cancer where it functions as a tumor suppressor, glioblastoma, breast, prostate, and gastric cancer, via its oncogenic function. However, studies on the underlying molecular mechanisms of the different roles of INF2 in diverse cancers are limited. This review comprehensively describes the structure, biochemical features, and primary pathogenic mutations of INF2.
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Forminas/genética , Forminas/metabolismo , Genes Supresores de Tumor , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Oncogenes , Actinas/metabolismo , Forminas/química , Humanos , Proteínas de Microfilamentos/metabolismo , Mitocondrias/metabolismo , Mutación , Dominios Proteicos , Procesamiento Proteico-Postraduccional , Transducción de SeñalRESUMEN
Dysregulation of the ubiquitin-proteasome pathway is strongly associated with cancer initiation and progression. Speckle-type POZ(pox virus and zinc finger protein) protein(SPOP) is an adapter protein of CUL3-based E3 ubiquitin ligase complexes. Gene expression profiling from the Cancer Genome Atlas (TCGA) suggests that SPOP is downregulated in testicular germ cell tumors (TGCTs), but the specific contribution of this protein remains to be explored. In this study, we show that the germ line-specific factor DPPA2 was identified as a proteolytic substrate for the SPOP-CUL3-RBX1 E3 ubiquitin-ligase complex. SPOP specifically binds to a SPOP-binding consensus (SBC) degron located in DPPA2 and targets DPPA2 for degradation via the ubiquitin-proteasome pathway. SPOP downregulation increases the expression of pluripotency markers OCT4 and Nanog but decreases that of early differentiation marker gene Fst. This effect is partly dependent on its activity toward DPPA2. In addition, the dysregulation of SPOP-DPPA2 axis contributes to the malignant transformation phenotypes of TGCT cells.
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Neoplasias de Células Germinales y Embrionarias/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Represoras/metabolismo , Neoplasias Testiculares/metabolismo , Factores de Transcripción/metabolismo , Ubiquitinación , Animales , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Xenoinjertos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/patología , Proteínas Nucleares/genética , Proteolisis , Proteínas Represoras/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologíaRESUMEN
OBJECTIVE: The safety and feasibility of retrograde laparoscopic resection of the left side of the liver. METHODS: Ninety-three laparoscopic left hepatic lobe cases were selected between August 2010 and August 2014 from our institution. A retrospective cohort study was performed between the antegrade partial hepatectomy group (47 cases; dissection from the first porta hepatis to the second) and the retrograde partial hepatectomy group (46 cases; dissection from the second porta hepatis to the first), to compare the length of time needed for resection, the amount of bleeding, post-operative time in the hospital, and the incidence of major complications, such as bile leakage, abdominal abscess, and post-hepatectomy hemorrhage. RESULTS: All of the cases had a successful laparoscopic partial hepatectomy without the need for an intraoperative blood transfusion. Patients were able to ambulate on post-operative day 1 and tolerated a liquid diet on post-operative day 1 or 2. There were no statistical differences of post-operative hospital length of stay or incidence of major complications between the two groups. Both duration of resection and the amount of bleeding were less in the retrograde group than of those in the antegrade group, due to the lower incidence of hepatic vein injury in the retrograde group. CONCLUSION: Occlusion of both the inflow and outflow hepatic vessels combined with retrograde hepatectomy from the second porta hepatis to the first, demonstrated less hemorrhage and lower incidence of hepatic veins injury during laparoscopic partial hepatectomy.
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Hepatectomía/métodos , Laparoscopía , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Colelitiasis/cirugía , Estudios de Cohortes , Estudios de Factibilidad , Femenino , Hemangioma/cirugía , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios RetrospectivosRESUMEN
BACKGROUND: The purpose of this study is to examine and analyse the outcomes and patient experiences associated with laparoscopic central pancreatectomy. METHODS: The perioperative data of 16 patients who underwent laparoscopic central pancreatectomy were retrospectively analysed at Ningbo Medical Center Lihuili Hospital (Xingning Branch and Eastern Branch) from September 2017 to July 2023. RESULTS: All surgical procedures were completed without the need for intraoperative conversion to open surgery. In two cases, intraoperative cholangiography was performed, while in four cases, intraoperative fluoroscopic laparoscopic assistance was utilized. The duration of the operations varied from 160 to 360 min, with an average of 281.75 min. The estimated volume of intraoperative bleeding ranged from 50 to 300 mL, with an average of 113.75 mL. The postoperative pathology results revealed that there were two cases of intraductal papillary mucinous neoplasm, six cases of serous cystic neoplasms, one case of mucinous cystic neoplasm, five cases of solid pseudopapillary neoplasms, and two cases of neuroendocrine tumours. The maximum diameter of the tumours ranged from 3.0 to 5.0 cm, with an average of 3.67 cm. There were no instances of postoperative common bile duct stenosis or biliary leakage. Among the cases, five did not exhibit pancreatic fistula, six experienced biochemical leakage, three had grade B pancreatic fistula, and two had grade C pancreatic fistula. CONCLUSION: Laparoscopic central pancreatectomy, as a method to preserve pancreatic function, entails specific surgical risks and a notable likelihood of postoperative pancreatic fistula, necessitating the expertise of seasoned surgeons for its execution.
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Laparoscopía , Pancreatectomía , Neoplasias Pancreáticas , Humanos , Pancreatectomía/métodos , Laparoscopía/métodos , Masculino , Femenino , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Tempo OperativoRESUMEN
We investigated the effect of chemical oxygen demand (COD)/N ratio on polyhydroxybutyrate (PHB) accumulating ability in an anaerobic/aerobic cycle sequential batch reactor (SBR). Compared the COD/N ratio of 10, 20, 50, and 125, the COD/N of 125 was the most suitable nutritional proportion. When COD was 1,200 mg/L and COD/N/P was 1,200/9.6/30, activated sludge PHB synthesis reached a maximum of 64.2 % of the dry weight of the cells. The population of the activated sludge was detected periodically by denaturing gradient gel electrophoresis (DGGE). The predominant strains belonged to five genera: Bacteroidetes sp., Acinetobacter sp., Betaproteobacteria sp., Gammaproteobacteria sp., Arcobacter sp., and Bacillus sp. Pyrosequencing analysis of the 16S rRNA gene indicated that the PHB synthesis community was more diverse than that was detected by DGGE, specifically Acidobacteria (12.25 %), Alphaproteobacteria (10.78 %), Actinomycetales (9.68 %), Actinobacteria (5.15 %), Proteobacteria (4.04 %), and unclassified bacteria (24.14 %).
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Bacterias/clasificación , Bacterias/metabolismo , Biota , Polihidroxialcanoatos/metabolismo , Aguas del Alcantarillado/microbiología , Aerobiosis , Anaerobiosis , Bacterias/genética , Bacterias/aislamiento & purificación , Análisis de la Demanda Biológica de Oxígeno , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Electroforesis en Gel de Gradiente Desnaturalizante , Nitrógeno/análisis , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
Background: Hepatocellular carcinoma (HCC) health challenge worldwide. Many studies showed that circadian rhythms play a critical role in tumor development. This study aimed to investigate the role of the circadian gene period2 (PER2) in HCC development and explore the possible mechanisms involved. Methods: From fresh HCC tissues and paired paracancerous tissues, we measured PER2 mRNA and protein expression levels and calculated the correlations between PER2 expression and clinicopathological parameters in patients with HCC. We used transcriptome data from The Cancer Genome Atlas to mine the PER2 gene, including single gene difference analysis, single gene co-expression analysis, gene set enrichment analysis, immune infiltration analysis, and methylation analysis to explore its role and mechanism in HCC occurrence and development. Results: PER2 expression levels were significantly lower in HCC tissues than in the paired paracancerous tissues. PER2 expression in HCC significantly correlated with neural invasion, Child-Pugh classification, and China liver cancer staging stage in HCC patients. The differentially expressed genes associated with PER2 were significantly enriched in mitochondrial oxidative phosphorylation, transcriptional translation, amino acid metabolism, and other related pathways. PER2 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes and positively correlated with TP53 expression in HCC tissues. The DNA methylation status in eight CpG islands of the PER2 gene was associated with HCC outcomes. Conclusion: PER2 is a potential diagnostic and prognostic biomarker and a promising therapeutic target in HCC.
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Hepatocellular carcinoma (HCC), ranking as the seventh most prevalent cancer worldwide, poses a significant health challenge. Actinidia chinensis Planch Root extracts (acRoots), a traditional Chinese medicine, has exhibited promising inhibitory effects on the proliferation, invasion, and migration of various cancer cell types. Nevertheless, its specific impact and underlying mechanisms concerning HCC remain unclear. This research aimed to elucidate the anticancer properties and potential molecular mechanisms of acRoots in the HepG2 and LM3 cell lines. Our findings demonstrate that acRoots effectively hampers the in vitro proliferation, migration, and invasion of HCC cells. Furthermore, acRoots induces apoptosis and autophagy by impeding the AKT/mTOR signaling pathway, with its inhibitory effects on cells being restored under AKT activator induction. This study, for the first time, elucidates that acRoots can suppress HepG2 and LM3 cell proliferation by blocking the Akt/mTOR pathway, thereby activating apoptosis and autophagy. These results underscore the potential of acRoots as a promising antitumor agent for HCC.
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Originally identified as a regulator of apoptosis and transcription, B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) has since been shown to be associated with a multitude of biological processes, such as DNA damage response, splicing and processing of pre-mRNA, T-cell activation, lung development, muscle cell proliferation and differentiation, autophagy, ischemia-reperfusion injury, and viral infection. In recent years, an increasing amount of evidence has shown that BCLAF1 acts as either a tumor promoter or tumor suppressor in tumorigenesis depending on the cellular context and the type of cancer. Even in the same tumor type, BCLAF1 may have opposite effects. In the present review, the subcellular localization, structural features, mutations within BCLAF1 will be described, then the regulation of BCLAF1 and its downstream targets will be analyzed. Furthermore, the different roles and possible mechanisms of BCLAF1 in tumorigenesis will also be highlighted and discussed. Finally, BCLAF1 may be considered as a potential target for cancer therapy in the future.
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Hepatocarcinogenesis is a complex multistep biological process involving genetic and epigenetic alterations that are accompanied by activation of oncoproteins and inactivation of tumor suppressors, which in turn results in Hepatocellular carcinoma (HCC), one of the common tumors with high morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) is the key to protein degradation and regulation of physiological and pathological processes, and E3 ligases are key enzymes in the UPS that contain a variety of subfamily proteins involved in the regulation of some common signal pathways in HCC. There is growing evidence that many structural or functional dysfunctions of E3 are engaged in the development and progression of HCC. Herein, we review recent research advances in HCC-associated E3 ligases, describe their structure, classification, functional roles, and discuss some mechanisms of the abnormal activation or inactivation of the HCC-associated signal pathway due to the binding of E3 to known substrates. In addition, given the success of proteasome inhibitors in the treatment of malignant cancers, we characterize the current knowledge and future prospects for targeted therapies against aberrant E3 in HCC.
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BACKGROUND: The aim of the present study was to investigate the antitumor properties of N-(N-[3,5-difluorophenacetyl]-1-alanyl)-S-phenylglycine t-butyl ester (DAPT) against hepatocellular carcinoma (HCC), as well as the underlying mechanism. METHODS: Immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay were used to determine the expression of Notch1 in HCC tissues. The expression of Notch1 in 3 HCC cell lines was evaluated by qRT-PCR and Western blot. The proliferation ability of cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Flow cytometry and Transwell assay were used to check the apoptosis and migration of HepG2 cells, respectively. Western blot was used to determine the expression level of Notch1, Hes1, Phosphatase and tensin homolog (PTEN), protein kinase B1 (AKT1), phosphorylated AKT1, mammalian target of rapamycin (mTOR), phosphorylated mTOR, intracellular adhesion molecule-1, vascular cell adhesion protein 1, matrix metalloproteinase (MMP)-2, MMP-9, and focal adhesion kinase in cells and tumor tissues. A HepG2 xenograft experiment was conducted to evaluate the in vivo antitumor properties of DAPT. RESULTS: Notch1 was found to be significantly upregulated in both HCC tissues and cell lines. DAPT significantly inhibited the proliferation and migration of HepG2 cells in a dose-dependent manner, accompanied by the suppression of Notch1/Hes1 signaling, inactivation of AKT/mTOR signaling, downregulation of MMPs, and decreased expression of adhesion molecules. The activation of Notch1/Hes1 or AKT/mTOR signaling removed the inhibitory effect of DAPT on the proliferation and migration of HepG2 cells, as well as the inhibitory properties of DAPT on the expression of MMPs and adhesion molecules. The antitumor properties and regulatory effect of DAPT against the extracellular matrix (ECM) and Hes1/PTEN/AKT/mTOR signaling were verified by the HepG2 xenograft experiments. CONCLUSIONS: DAPT could suppress the proliferation and migration of HCC by regulating the ECM and inhibiting the Hes1/PTEN/AKT/mTOR signaling pathway.
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BACKGROUND: Breathing exercises can improve the symptoms of patients with gastroesophageal reflux disease (GERD), but their specific effect and function are disputed. To evaluate and conduct a meta-analysis on the effect of breathing exercises on patients with GERD. METHODS: A literature search for randomized controlled trials (RCTs) and prospective studies on the effects of employing breathing exercises on patients with GERD was conducted of all major online English databases (PubMed, Embase, the Cochrane library, CENTRAL, Web of Science, AMED, and CINAHL). After the systematic review of all the studies according to inclusion and exclusion criteria, we analyzed the extracted data through meta-analysis by using RevMan 5.3 software. RESULTS: This thesis analyzes 7 studies (including three RCTs), which together involved 194 patients and 16 healthy volunteers. The primary outcomes of these studies included GERD symptoms, esophageal manometry, esophageal pH monitoring, laryngoscopic findings, and acid suppression usage. The results of meta-analysis indicate that breathing exercises can improve pressure generated by the lower oesophageal sphincter (LES), and a statistically significant difference was observed. The possible mechanism behind this is the enhancement of the anti-regurgitation barrier [especially crural diaphragm (CD) tension]. CONCLUSIONS: To some extent, breathing exercises can relieve the symptoms of patients with GERD.
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Ejercicios Respiratorios/métodos , Terapia por Ejercicio/métodos , Reflujo Gastroesofágico/terapia , Femenino , Humanos , Masculino , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Pruebas de Función RespiratoriaRESUMEN
Recurrent oncogenic mutations of MyD88 have been identified in a variety of lymphoid malignancies. Gain-of-function mutations of MyD88 constitutively activate downstream NF-κB signaling pathways, resulting in increased cellular proliferation and survival. However, whether MyD88 activity can be aberrantly regulated in MyD88-wild-type lymphoid malignancies remains poorly understood. SPOP is an adaptor protein of CUL3-based E3 ubiquitin ligase complex and frequently mutated genes in prostate and endometrial cancers. In this study, we reveal that SPOP binds to and induces the nondegradative ubiquitination of MyD88 by recognizing an atypical SPOP-binding motif in MyD88. This modification blocks Myddosome assembly and downstream NF-κB activation. SPOP is mutated in a subset of lymphoid malignancies, including diffuse large B-cell lymphoma (DLBCL). Lymphoid malignancies-associated SPOP mutants exhibited impaired binding to MyD88 and suppression of NF-κB activation. The DLBCL-associated, SPOP-binding defective mutants of MyD88 escaped from SPOP-mediated ubiquitination, and their effect on NF-κB activation is stronger than that of wild-type MyD88. Moreover, SPOP suppresses DLBCL cell growth in vitro and tumor xenograft in vivo by inhibiting the MyD88/NF-κB signaling. Therefore, SPOP acts as a tumor suppressor in DLBCL. Mutations in the SPOP-MyD88 binding interface may disrupt the SPOP-MyD88 regulatory axis and promote aberrant MyD88/NF-κB activation and cell growth in DLCBL.
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Linfoma de Células B Grandes Difuso/prevención & control , Factor 88 de Diferenciación Mieloide/antagonistas & inhibidores , FN-kappa B/antagonistas & inhibidores , Proteínas Nucleares/metabolismo , Proteínas Represoras/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismo , Apoptosis , Proliferación Celular , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Mutación , Proteínas Nucleares/genética , Proteínas Represoras/genética , Células Tumorales Cultivadas , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
The objective of this study was to predict the total viable counts (TVC) and total volatile basic nitrogen (TVB-N) in pork using an electronic nose (E-nose), and to assess the freshness of chilled pork during storage using different packaging methods, including pallet packaging (PP), vacuum packaging (VP), and modified atmosphere packaging (MAP, 40% O2 /40% CO2 /20% N2 ). Principal component analysis (PCA) was used to analyze the E-nose signals, and the results showed that the relationships between the freshness of chilled pork and E-nose signals could be distinguished in the loadings plots, and the freshness of chilled pork could be distributed along 2 first principal components. Multiple linear regression (MLR) was used to correlate TVC and TVB-N to E-nose signals. High F and R2 values were obtained in the MLR output of TVB-N (F = 32.1, 21.6, and 24.2 for PP [R2 = 0.93], VP [R2 = 0.94], and MAP [R2 = 0.95], respectively) and TVC (F = 34.2, 46.4, and 7.8 for PP [R2 = 0.98], VP [R2 = 0.89], and MAP [R2 = 0.85], respectively). The results of this study suggest that it is possible to use the E-nose technology to predict TVB-N and TVC for assessing the freshness of chilled pork during storage.