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Although surgical resection could provide better survival for patients with colorectal cancer liver metastases (CRLM), the recurrence rate after resection of CRLM remains high. The progress of genome sequencing technologies has greatly improved the molecular understanding of colorectal cancer. In the era of genomics and targeted therapy, genetic mutation analysis is of great significance to guide systemic treatment and identify patients who can benefit from resection of CRLM. RAS and BRAF mutations and microsatellite instability/deficient deoxyribonucleic acid (DNA) mismatch repair status have been incorporated into current clinical practice. Other promising molecular biomarkers such as coexisting gene mutations and circulating tumor DNA are under active investigation. This study aimed to review the prognostic significance of molecular biomarkers in patients with CRLM undergoing metastasectomy based on the current evidence.
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BACKGROUND: Tumor cells display augmented capability to maintain endoplasmic reticulum (ER) homeostasis and hijack ER stress pathway for malignant phenotypes under microenvironmental stimuli. Metabolic reprogramming is a well-known hallmark for tumor cells to provide specific adaptive traits to the microenvironmental alterations. However, it's unknown how tumor cells orchestrate metabolic reprogramming and tumor progression in response to ER stress. Herein, we aimed to explore the pivotal roles of SEC63-mediated metabolic remodeling in hepatocellular carcinoma (HCC) cell metastasis after ER stress. METHODS: The expression levels of SEC63 in HCC tissues and adjacent non-cancerous tissues were determined by immunohistochemistry and western blot. The regulatory roles of SEC63 in HCC metastasis were investigated both in vitro and in vivo by RNA-sequencing, metabolites detection, immunofluorescence, and transwell migration/invasion analyses. GST pull-down, immunoprecipitation/mass spectrometry and in vivo ubiquitination/phosphorylation assay were conducted to elucidate the underlying molecular mechanisms. RESULTS: We identified SEC63 as a new regulator of HCC cell metabolism. Upon ER stress, the phosphorylation of SEC63 at T537 by IRE1α pathway contributed to SEC63 activation. Then, the stability of ACLY was upregulated by SEC63 to increase the supply of acetyl-CoA and lipid biosynthesis, which are beneficial for improving ER capacity. Meanwhile, SEC63 also entered into nucleus for increasing nuclear acetyl-CoA production to upregulate unfolded protein response targets to improve ER homeostasis. Importantly, SEC63 coordinated with ACLY to epigenetically modulate expression of Snail1 in the nucleus. Consequently, SEC63 promoted HCC cell metastasis and these effects were reversed by ACLY inhibition. Clinically, SEC63 expression was significantly upregulated in HCC tissue specimens and was positively correlated with ACLY expression. Importantly, high expression of SEC63 predicted unfavorable prognosis of HCC patients. CONCLUSIONS: Our findings revealed that SEC63-mediated metabolic reprogramming plays important roles in keeping ER homeostasis upon stimuli in HCC cells. Meanwhile, SEC63 coordinates with ACLY to upregulate the expression of Snail1, which further promotes HCC metastasis. Metastasis is crucial for helping cancer cells seek new settlements upon microenvironmental stimuli. Taken together, our findings highlight a cancer selective adaption to ER stress as well as reveal the potential roles of the IRE1α-SEC63-ACLY axis in HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Endorribonucleases/genética , Acetilcoenzima A/genética , Acetilcoenzima A/metabolismo , Acetilcoenzima A/farmacologia , Linhagem Celular Tumoral , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Estresse do Retículo Endoplasmático , Regulação Neoplásica da Expressão GênicaRESUMO
Colorectal cancer (CRC) is one of the most popular malignancies globally, with 930 000 deaths in 2020. The evaluation of CRC-related pathogenesis and the discovery of potential therapeutic targets will be meaningful and helpful for improving CRC treatment. With huge efforts made in past decades, the systematic treatment regimens have been applied to improve the prognosis of CRC patients. However, the sensitivity of CRC to chemotherapy and targeted therapy is different from person to person, which is an important cause of treatment failure. The emergence of patient-derived xenograft (PDX) models shows great potential to alleviate the straits. PDX models possess similar genetic and pathological characteristics as the features of primary tumors. Moreover, PDX has the ability to mimic the tumor microenvironment of the original tumor. Thus, the PDX model is an important tool to screen precise drugs for individualized treatment, seek predictive biomarkers for prognosis supervision, and evaluate the unknown mechanism in basic research. This paper reviews the recent advances in constructed methods and applications of the CRC PDX model, aiming to provide new knowledge for CRC basic research and therapeutics.
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Neoplasias Colorretais , Pesquisa Translacional Biomédica , Animais , Humanos , Ensaios Antitumorais Modelo de Xenoenxerto , Pesquisa Translacional Biomédica/métodos , Xenoenxertos , Modelos Animais de Doenças , Neoplasias Colorretais/patologia , Microambiente TumoralRESUMO
BACKGROUND: To compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic versus open pancreaticoduodenectomy (LPD vs. OPD), we performed a meta-analysis of currently available propensity score matching studies and large-scale retrospective cohorts to compare the safety and overall effect of LPD to OPD for patients with PDAC. METHODS: A meta-analysis was registered at PROSPERO and the registration number is CRD42021250395. PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Data on operative times, blood loss, 30-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien-Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, overall survival, and long-term survival) were subjected to meta-analysis. RESULTS: Overall, we identified 10 retrospective studies enrolling a total of 11,535 patients (1,514 and 10,021 patients underwent LPD and OPD, respectively). The present meta-analysis showed that there were no significant differences in overall survival time, 1-year survival, 2-year survival, 30-day mortality, Clavien-Dindo ≥3 complications, POPF, DGE, PPH, and lymph node dissection between the LPD and OPD groups. Nevertheless, compared with the OPD group, LPD resulted in significantly higher rate of R0 resection (OR: 1.22; 95% CI 1.06-1.40; p = 0.005), longer operative time (WMD: 60.01 min; 95% CI 23.23-96.79; p = 0.001), lower Clavien-Dindo grade ≥III rate (p = 0.02), less blood loss (WMD: -96.49 ml; 95% CI -165.14 to -27.83; p = 0.006), lower overall morbidity rate (OR: 0.65; 95% CI 0.50 to 0.85; p = 0.002), shorter LOS (MD = -2.73; 95% CI -4.44 to -1.03; p = 0.002), higher 4-year survival time (p = 0.04), 5-year survival time (p = 0.001), and earlier time to starting adjuvant chemotherapy after surgery (OR: -10.86; 95% CI -19.42 to -2.30; p = 0.01). CONCLUSIONS: LPD is a safe and feasible alternative to OPD for patients with PDAC, and compared with OPD, LPD seemed to provide a similar OS. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.
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To explore the updated evaluation about the obstetrical and perioperative outcomes of laparoscopic appendicectomy (LA) for pregnancy appendicitis compared with open appendicectomy (OA). Two reviewers independently searched the PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science databases to screen eligible studies up to December 2020. Only clinical researches, no < 10 cases for LA and OA group were included. Twenty retrospective studies with 7,248 pregnant women, evaluating LA and OA in surgical and obstetrical outcomes, were included. The weighted mean difference (WMD) with 95% CI and odds ratio (OR) was used to compare continuous and dichotomous variables. It seems LA was connected with significantly shorter hospital time and lower wound infection [mean difference (MD), -0.57 days; 95% CI, -0.96 to -0.18; p = 0.004 and OR, 0.34; 95% CI, 0.18 to 0.62; p = 0.0005, respectively]. The incidence of fetal loss after LA was higher than OA (OR,1.93; 95% CI, 1.39-2.69; p < 0.0001). It was almost similar in the rate of preterm delivery (OR, 0.80; 95% CI, 0.48 to 1.34; p = 0.40) and other perioperative and obstetrical complications (p > 0.05). Our results indicated that the occurrence of fetal loss after LA should not be ignored. Caution, skillful operation, and thoroughly informed consent about the advantages and disadvantages of laparoscopy are necessary. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42021233150.
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Background: Although laparoscopic pancreaticoduodenectomy (LPD) is a safe and feasible treatment compared with open pancreaticoduodenectomy (OPD), surgeons need a relatively long training time to become technically proficient in this complex procedure. In addition, the incidence of complications and mortality of LPD will be significantly higher than that of OPD in the initial stage. This meta-analysis aimed to compare the safety and overall effect of LPD to OPD after learning curve based on eligible large-scale retrospective cohorts and randomized controlled trials (RCTs), especially the difference in the perioperative and short-term oncological outcomes. Methods: PubMed, Web of Science, EMBASE, Cochrane Central Register, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Only clinical studies reporting more than 40 cases for LPD were included. Data on operative times, blood loss, and 90-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien-Dindo ≥III complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, positive lymph node numbers, and tumor size) were subjected to meta-analysis. Results: Overall, the final analysis included 13 retrospective cohorts and one RCT comprising 2,702 patients (LPD: 1,040, OPD: 1,662). It seems that LPD has longer operative time (weighted mean difference (WMD): 74.07; 95% CI: 39.87-108.26; p < 0.0001). However, compared with OPD, LPD was associated with a higher R0 resection rate (odds ratio (OR): 1.43; 95% CI: 1.10-1.85; p = 0.008), lower rate of wound infection (OR: 0.35; 95% CI: 0.22-0.56; p < 0.0001), less blood loss (WMD: -197.54 ml; 95% CI -251.39 to -143.70; p < 0.00001), lower blood transfusion rate (OR: 0.58; 95% CI 0.43-0.78; p = 0.0004), and shorter LOS (WMD: -2.30 day; 95% CI -3.27 to -1.32; p < 0.00001). No significant differences were found in 90-day mortality, overall morbidity, Clavien-Dindo ≥ III complications, reoperation, POPF, DGE, PPH, lymph node dissection, positive lymph node numbers, and tumor size between LPD and OPD. Conclusion: Comparative studies indicate that after the learning curve, LPD is a safe and feasible alternative to OPD. In addition, LPD provides less blood loss, blood transfusion, wound infection, and shorter hospital stays when compared with OPD.
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Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and its incidence continues to increase year by year. Endoplasmic reticulum stress (ERS) caused by protein misfolding within the secretory pathway in cells and has an extensive and deep impact on cancer cell progression and survival. Growing evidence suggests that the genes related to ERS are closely associated with the occurrence and progression of HCC. This study aimed to identify an ERS-related signature for the prospective evaluation of prognosis in HCC patients. RNA sequencing data and clinical data of patients from HCC patients were obtained from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC). Using data from TCGA as a training cohort (n=424) and data from ICGC as an independent external testing cohort (n=243), ERS-related genes were extracted to identify three common pathways IRE1, PEKR, and ATF6 using the GSEA database. Through univariate and multivariate Cox regression analysis, 5 gene signals in the training cohort were found to be related to ERS and closely correlated with the prognosis in patients of HCC. A novel 5-gene signature (including HDGF, EIF2S1, SRPRB, PPP2R5B and DDX11) was created and had power as a prognostic biomarker. The prognosis of patients with high-risk HCC was worse than that of patients with low-risk HCC. Multivariate Cox regression analysis confirmed that the signature was an independent prognostic biomarker for HCC. The results were further validated in an independent external testing cohort (ICGC). Also, GSEA indicated a series of significantly enriched oncological signatures and different metabolic processes that may enable a better understanding of the potential molecular mechanism mediating the progression of HCC. The 5-gene biomarker has a high potential for clinical applications in the risk stratification and overall survival prediction of HCC patients. In addition, the abnormal expression of these genes may be affected by copy number variation, methylation variation, and post-transcriptional regulation. Together, this study indicated that the genes may have potential as prognostic biomarkers in HCC and may provide new evidence supporting targeted therapies in HCC.
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BACKGROUND: To compare perioperative and short-term oncologic outcomes of laparoscopic pancreaticoduodenectomy (LPD) to open pancreaticoduodenectomy (OPD) using data from large-scale retrospective cohorts and randomized controlled trials (RCTs) in the last 10 years. METHODS: A meta-analysis to assess the safety and feasibility of LDP and OPD registered with PROSPERO: (CRD42020218080) was performed according to the PRISMA guidelines. Studies comparing LPD with OPD published between January 2010 and October 2020 were included; only clinical studies reporting more than 30 cases for each operation were included. Two authors performed data extraction and quality assessment independently. The primary endpoint was operative times, blood loss, and 90 days mortality. Secondary endpoints included reoperation, length of hospital stay (LOS), morbidity, Clavien-Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0-resection, lymph node dissection). RESULTS: Overall, the final analysis included 15 retrospective cohorts and 3 RCTs comprising 12,495 patients (2,037 and 10,458 patients underwent LPD and OPD). It seems OPD has more lymph nodes harvested but no significant differences [weighted mean difference (WMD): 1.08; 95% confidence interval (CI): 0.02 to 2.14; P=0.05]. Nevertheless, compared with OPD, LPD was associated with a higher R0 resection rate [odds ratio (OR): 1.26; 95% CI: 1.10-1.44; P=0.0008] and longer operative time (WMD: 89.80 min; 95% CI: 63.75-115.84; P<0.00001), patients might benefit from lower rate of wound infection (OR: 0.36; 95% CI: 0.33-0.59; P<0.0001), much less blood loss (WMD: -212.25 mL; 95% CI: -286.15 to -138.14; P<0.00001) and lower blood transfusion rate (OR: 0.58; 95% CI: 0.43-0.77; P=0.0002) and shorter LOS (WMD: -1.63 day; 95% CI: -2.73 to -0.51; P=0.004). No significant differences in 90-day mortality, overall morbidity, Clavien-Dindo ≥3 complications, reoperation, POPF, DGE and PPH between LPD and OPD. CONCLUSIONS: Our study suggests that after learning curve, LPD is a safe and feasible alternative to OPD as it provides similar perioperative and acceptable oncological outcomes when compared with OPD.
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BACKGROUND: Circulating plasma mRNAs can be analyzed to identify putative cancer biomarkers. This study was conducted in an effort to detect plasma mRNA biomarkers capable of predicting pancreatic cancer (PACA) patient prognosis. Material and Methods. First, prognostic mRNAs that were differentially expressed in PACA in The Cancer Genome Atlas (TCGA) were established, after which microarray expression profiles from PACA patient plasma samples were utilized to specifically identify potential prognostic plasma mRNA biomarkers associated with this cancer type. In total, plasma samples were then collected from 79 PACA patients and 19 healthy controls to confirm differential mRNA expression via qPCR, while Kaplan-Meier analyses were used to examine the link between mRNA expression and patient overall survival. RESULTS: In total, three prognostic differentially expressed genes were identified in PACA patient plasma samples, including SMAP2, PTPN6, and EVL (Ena/VASP-like). Plasma EVL levels were confirmed via qPCR to be correlated with tumor pathology (p < 0.01), while the overall survival of patients with low plasma EVL levels was poor (p < 0.01). Multivariate Cox regression analyses further confirmed that plasma EVL levels were independent predictors of PACA patient prognosis. CONCLUSION: We found that PACA is associated with the downregulation of plasma EVL mRNA levels, indicating that this mRNA may be a viable biomarker associated with patient prognosis.
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Appropriate drainage duration is vital for the postoperative rehabilitation of patients with breast cancer (BC) undergoing modified radical mastectomy (MRM). To provide better and individualized postoperative management for these patients, this study explored independent predictors of postoperative drainage duration in patients with BC. This was a single-center retrospective cohort study. Patients diagnosed with BC and treated with MRM from May 2016 to April 2020 were randomly divided into training (n = 729) and validation (n = 243) cohorts. Univariate and multivariate Cox analyses revealed that the body mass index, serum albumin level, hypertension, number of total dissected axillary lymph nodes, and ratio of positive axillary lymph nodes were independent predictors of postoperative drainage duration in the training cohort. Based on independent predictors, a nomogram was constructed to predict the median postoperative drainage duration and the probability of retaining the suction drain during this period. This nomogram had good concordance and discrimination both in the training and validation cohorts and could effectively predict the probability of retaining the suction drain during drainage, thus assisting clinicians in predicting postoperative drainage duration and providing individualized postoperative management for patients with BC.
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Neoplasias da Mama/cirurgia , Drenagem , Mastectomia Radical Modificada , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Tomada de Decisão Clínica , Gerenciamento Clínico , Drenagem/métodos , Feminino , Humanos , Mastectomia Radical Modificada/métodos , Pessoa de Meia-Idade , Nomogramas , Curva ROC , Resultado do TratamentoRESUMO
INTRODUCTION: Pancreatic adenocarcinoma (PAAD) is among the deadliest forms of cancer globally. Carbonic anhydrase 12 (CA12) is known to play central roles in regulating many cancers, but its function in the context of PAAD is rarely discussed. This study was, therefore, designed to assess the expression of CA12 in PAAD and to explore its underlying mechanistic role in this cancer type. METHODS: Immunohistochemical staining was used to measure CA12 expression in PAAD samples. The functionality of pancreatic cancer cells expressing varying levels of CA12 was assessed through wound healing, Transwell, and CCK-8 assays. In addition, flow cytometry was used to measure apoptosis and cell cycle progression in these same cells, while Western blotting was used to analyze the expression of proteins associated with the NF-κB signaling pathway. RESULTS: PAAD tissue samples exhibited significant CA12 downregulation (P < 0.001), and lower CA12 expression was, in turn, associated with poorer overall survival (P < 0.001). CA12 overexpression significantly impaired the proliferation of PAAD cell lines, instead inducing their apoptotic death and G0/G1 phase cell cycle arrest (P < 0.05). We additionally found that CA12 may exert its tumor suppressive roles via modulating the NF-κB signaling pathway. CONCLUSION: These results indicate that CA12 functions as a tumor suppressor in PAAD and may thus be a novel therapeutic target that can be used to guide PAAD patient treatment.
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Apoptose/genética , Anidrases Carbônicas/genética , NF-kappa B/genética , Neoplasias Pancreáticas/genética , Transdução de Sinais/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Prognóstico , Fase de Repouso do Ciclo Celular/genéticaRESUMO
Due to the difficulties in early diagnosis of pancreatic adenocarcinoma (PAAD), many patients fail to receive optimal therapeutic regimens. The Secretory-Carrier-Membrane-Proteins (SCAMPs) are known to be dysregulated in a range of human diseases due to their characterized roles in mammalian cell exocytosis inferred from their functions as integral membrane proteins. However, the expression and prognostic value of SCAMPs in PAAD is poorly characterized. We compared cancer vs. healthy tissue and found that the expression of SCAMPs1-4 was upregulated in PAAD compared to normal tissue. In contrast, SCAMP5 expression was downregulated in PAAD. Moreover, the expression of SCAMPs1-4 was enhanced in PAAD cell lines according to Cancer Cell Line public database. Furthermore, the HPA, GEPIA databases and immunohistochemical analysis from 238 patients suggested that the loss of SCAMP1 led to improved overall survival (OS), whilst lower SCAMP5 levels led to a poorer OS. The univariate and multivariate analysis showed that SCAMP1 and SCAMP5 expression were independent prognostic factors of PAAD. In addition, the cBioPortal for Cancer Genomics, LinkedOmics datasets, and the GEPIA were used to identify the co-expression genes of SCAMP1,5 and the correlation between SCAMPs members. We conclude that SCAMPs 1 and 5 significantly represent promising diagnosis and prognostic biomarkers.
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Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Proteínas de Transporte/genética , Regulação para Baixo , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Mensageiro/metabolismo , Taxa de Sobrevida , Transcriptoma , Regulação para Cima , Proteínas de Transporte Vesicular/genéticaRESUMO
COL17A1 (collagen type XVII alpha 1 chain) is known to be upregulated and has a prognostic role in many malignancies, as well as contributing to cell proliferation, apoptosis, and invasion. However, little knowledge is available on the expression and prognostic value of COL17A1 in pancreatic adenocarcinoma (PDAC). In our study, we searched the public database and found that mRNA and protein levels of COL17A1 are commonly upregulated in PDAC tissues. The immunohistochemical analysis conducted by us revealed enhanced expression of COL17A1 protein in 169 PDAC samples compared with that in 67 adjacent normal tissues. We also observed a significantly positive correlation between COL17A1 expression and lymph node metastasis (p < 0.0001), TNM clinical stage (p < 0.0001), and pathology differentiation (p < 0.01). The KM-plot results indicated that PDAC patients with a high COL17A1 expression have a poorer overall survival (p < 0.001) than those with a low COL17A1 expression. The result of the Cox regression analysis of multivariate data suggested COL17A1 is an independent prognostic indicator of PDAC patients' overall survival. CCK-8, wound healing, and transwell assays suggested that COL17A1 knockdown markedly inhibited tumor proliferation and invasion in PDAC cells, and cells with COL17A1 overexpression had a prominently higher proliferative and invasive capacity. Knockdown of COL17A1 significantly upregulated the apoptosis rate. We deduce that upregulated COL17A1 activated the NF-κB pathway in PDAC cells. In summary, our studies showed the prognostic value of COL17A1 in PDAC and that COL17A1 may act as a molecular therapeutic target for PDAC treatment.
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BACKGROUND: Ambulatory cancer patients carry a high risk of venous thromboembolism (VTE). However, the optimal prophylaxis strategy remains controversial. This meta-analysis compared the effectiveness and safety of apixaban, rivaroxaban, low molecular weight heparin (LMWH), semuloparin, aspirin, and warfarin for the prevention of VTE in ambulatory cancer patients. METHODS: A systematic review and network meta-analysis was performed. PubMed, the Cochrane Central Register of Controlled Trails (CENTRAL) and EMBASE electronic databases were searched from inception to 26 April 2019. In the meta-analysis, 19 randomized controlled trials (RCTs) in ambulatory cancer patients administrated venous thromboprophylaxis agents were included. The primary outcome was the risk of VTE. Safety outcomes included the occurrence of major-bleeding. Two investigators identified the studies and performed data extraction. A network meta-analysis was performed and agents were ranked using cumulative ranking (SUCRA) probabilities. RESULTS: We identified 19 studies, including 11,430 patients comparing 10 interventions. Compared to placebo controls, apixaban (5 mg) showed the highest efficacy for the prevention of VTE [odds ratio (OR) 0.36, 95% confidence interval (CI): 0.18-0.71, SUCRA=69.5] and was more effective than LMWH (OR 0.5, 0.39-0.63; SUCRA=52.1) or warfarin (OR 0.75, 95% CI: 0.35-1.59; SUCRA=25.6). Moreover, the safety of apixaban (5 mg) (OR 1.41, 95% CI: 0.33-5.93; SUCRA=58.5) was higher than LMWH (OR 1.96, 95% CI: 0.99-3.86; SUCRA=44.1) or warfarin (OR 3.06, 95% CI: 1.03-9.08; SUCRA=29.1). There were no significant differences between placebo and experimental groups in terms of patient deaths. CONCLUSIONS: Anticoagulation therapies in ambulatory cancer patients can significantly reduce the risk of VTE. However, this protective effect was associated with a significantly increased risk of major bleeding. Apixaban at the appropriate dose can decrease the risk of VTE without increasing the bleeding risk. These findings require validation in larger study cohorts.
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Neoplasias , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Neoplasias/tratamento farmacológico , Metanálise em Rede , Tromboembolia Venosa/prevenção & controleRESUMO
When the skin barrier is damaged, surgical dressings are often used to cover wounds, sustain skin barrier, protect the injured area, prevent bacterial infection, and promote wound healing. However, at present, traditional dressings will be come stiffing as it absorbs the exudates of wound and sometimes cause secondary injury to the wound during the application process, which aggravate the pain of patients without analgesic effect. For this reason, the medical staff from Northern Jiangsu People's Hospital designed a new antibacterial analgesic dressing that can reduce the pain and increase the antibacterial ability. The dressings provide a sterile, moist environment to facilitate wound healing. Meanwhile, this dressing has the advantages of low cost, safeness and effectiveness, which can reduce the frequency of dressing changes, the possibility of wound infection, the pain and the medical expenses, which is worthy of clinical promotion.
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Bandagens , Cicatrização , Analgésicos , Antibacterianos , Humanos , Infecção da Ferida CirúrgicaRESUMO
PURPOSE: Cavotricuspid isthmus (CTI) ablation is an effective procedure for typical atrial flutter (AFL), but patients remain at an elevated risk for developing new atrial fibrillation (AF). Currently, there are limited data on the utility of CHA2DS2-VASc score to predict new-onset AF after typical AFL ablation. In this study, we assessed whether the CHA2DS2-VASc score is a useful predictor of new-onset AF after CTI ablation in typical AFL patients without a prior history of AF. METHODS: This was a retrospective study of 103 typical AFL patients with no prior history of AF, who underwent successful CTI ablation. The endpoint was occurrence of new-onset AF during follow-up. RESULTS: During a mean follow-up period of 24.6 ± 16.9 months, at least one episode of AF occurred in 33 (32%) patients. Multivariate Cox regression analysis revealed that CHA2DS2-VASc score (hazard ratio = 1.736; 95% confidence interval = 1.370-2.201; P < 0.001) was significantly associated with postablation new-onset AF (area under the curve = 0.797). A cutoff value of three stratified these patients into two groups with different incidences of postablation new-onset AF (67.9 vs. 18.7%, P < 0.001). CONCLUSION: The CHA2DS2-VASc score is a useful tool for the prediction of new-onset AF after ablation of typical AFL. Patients with CHA2DS2-VASc score ≥3 are more likely to develop new-onset AF and should be monitored more closely.
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Plastin-3 plays a key role in cancer cell proliferation and invasion, but its prognostic value in pancreatic cancer (PACA) remains poorly defined. In this study, we show that PLS3 messenger RNA is overexpressed in PACA tissue compared with normal tissue. We accumulated 207 cases of PACA specimens to perform immunohistochemical analysis and demonstrated that PLS3 levels correlate with T-classification (p < .001) and pathology (p < .001). Furthermore, overall survival rates (p < .001) in tumors with high PLS3 expression were poor, as assessed through Kaplan-Meier survival analysis. PLS3 was found to be an independent prognostic factor for PACA through multivariate Cox regression analysis. Moreover, we found that PLS3 enhances the proliferation and invasion of tumor cells as assessed through Cell Counting Kit-8, wounding healing assays, and Transwell assays. The upregulation of PLS3 also led to enhanced phosphatidylinositol-3 kinase/protein kinase B signaling in PACA cells. These data suggest that PLS3 is a biomarker to estimate PACA progression and represents a molecular target for PACA therapy.
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Proliferação de Células/fisiologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Neoplasias Pancreáticas/diagnóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais/genética , Neoplasias PancreáticasRESUMO
BACKGROUND: Pancreatic cancer frequently results in celiac artery invasion, resulting in an unresectable disease that generally has a median survival period of 6-11 months. Efforts to achieve curative resection of such tumors have been made by conducting distal pancreatectomy with en bloc celiac axis resection (DP-CAR) in some patients, but the long-term outcome data associated with this approach or its overall value remain to be clarified. METHODS: This meta-analysis was conducted to systematically assess the clinical efficacy of the DP-CAR treatment of unresectable tumors of the pancreatic body or tail (registered with PROSPERO: CRD42019129612). The PubMed, EMBASE, the Cochrane Library, and Web of Science databases were searched to identify relevant retrospective studies pertaining to such treatment. RESULTS: Overall, 12 retrospective cohort analyses incorporating 213 total DP-CAR cases and 911 DP cases were incorporated into the present meta-analysis. Pooled analyses demonstrated that relative to DP, DP-CAR was related to a longer operative duration [mean difference (MD) -73.69, 95% confidence interval (CI): -112.99 to -34.38, P=0.0002] and higher blood transfusion rates [odds ratio (OR) 0.29, 95% CI: 0.10 to 0.87; P=0.03]. DP-CAR was also linked to increased rates of PV resection (OR 0.17, 95% CI: 0.07 to 0.39; P<0.001) and delayed gastric emptying (DGE) (OR 0.37, 95% CI: 0.15 to 0.93, P=0.03). In contrast, R0 resection rates were higher in the DP group (OR 2.79, 95% CI: 1.90 to 4.09, P<0.001), and these patients also had a significantly improved prognosis (median survival time, 27.0 vs. 17.7 months; P<0.01) relative to the DP-CAR group. CONCLUSIONS: This analysis indicates that DP-CAR is not an effective means of improving R0 rates. However, available studies suggest that it is nonetheless a potentially valuable treatment option for pancreatic cancer patients with celiac axis involvement, and it is associated with a reasonable median survival duration of 17.7 months.
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Clinical doctors rarely associate hyperparathyroidism with significant bradyarrhythmia. We report a rare case of a patient initially misdiagnosed with primary sick sinus syndrome, which was eventually shown to be secondary to primary hyperparathyroidism.