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BACKGROUND: The optimal therapeutic strategy for patients with cT4bM0 esophageal cancer is controversial and varies internationally. This study aimed to describe treatment and survival of patients with cT4bM0 esophageal cancer in the Netherlands. METHODS: Patients staged with cT4bM0 esophageal cancer who were registered in the Netherlands Cancer Registry (NCR) were included. All patients were categorized by the treatment modality received. The Kaplan-Meier method was used to estimate the overall survival of them. RESULTS: Between 2015-2020, 286 patients with cT4bM0 esophageal cancer were included. Treatment consisted of preoperative chemoradiotherapy/chemotherapy followed by surgery (8%), chemoradiotherapy alone (35%), chemotherapy alone (6%), radiotherapy alone (19%) and best supportive care (32%). The median follow-up was 28.1 months. The 1-, 3-, and 5-year survival rates of each group were: 82%, 58%, 49% for preoperative therapy plus surgery; 53%, 27%, 16% for chemoradiotherapy only; 13%, 0%, 0% for chemotherapy only; 13%, 0%, 0% for radiotherapy only; and 5%, 0%, 0% for best supportive care. CONCLUSION: In a selected group of patients, preoperative therapy followed by esophagectomy may lead to improved survival, which is comparable to patients with <cT4bM0 tumors. Therefore, reevaluation following chemo(radio)therapy is recommended in these patients to evaluate the possibility of additional surgical resection.
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OBJECTIVE: To clarify the impact of the preoperative time intervals on short-term postoperative and pathological outcomes in esophageal cancer patients who underwent neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. SUMMARY BACKGROUND DATA: The impact of preoperative intervals on esophageal cancer patients who received multimodality treatment remains unknown. METHODS: Patients(cT1-4aN0-3M0) treated with nCRT plus esophagectomy were included using the Dutch national DUCA-database. Multivariate logistic regression was used to determine the effect of different time intervals upon short-term postoperative and pathological outcomes: diagnosis-to-nCRT intervals (≤5, 5-8 and 8-12 wk), nCRT-to-surgery intervals (5-11, 11-17 and >17 wk) and total preoperative intervals (≤16, 16-25 and >25 wk). RESULTS: Between 2010-2021, a total of 5052 patients were included. Compared to diagnosis-to-nCRT interval ≤5 weeks, the interval 8-12 weeks was associated with higher risk of overall complications (P=0.049). Compared to nCRT-to-surgery interval 5-11 weeks, the longer intervals (11-17 wk and >17 wk) were associated with higher risk of overall complications (P-value=0.016; P-value<0.001) and anastomotic leakage (P-value=0.004; P-value=0.030), but the interval >17 weeks was associated with lower risk of ypN+ (P-value=0.021). The longer total preoperative intervals were not associated with the risk of 30-day mortality and complications compared to the interval ≤16 weeks, but the longer total preoperative interval (>25 wk) was associated with higher ypT stage (P-value=0.010) and lower pCR rate (P-value=0.013). CONCLUSION: In patients with esophageal cancer undergoing nCRT and esophagectomy, prolonged preoperative time intervals may lead to higher morbidity and disease progression, and the causal relationship requires further confirmation.
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Peripheral vascular disease (PVD) is an emerging public health burden with a high rate of disability and mortality. Gasdermin D (GSDMD) has been reported to exert pyroptosis and play a critical role in the pathophysiology of many cardiovascular diseases. We ought to determine the role of GSDMD in the regulation of perfusion recovery after hindlimb ischemia (HLI). Our study revealed that GSDMD-mediated pyroptosis occurred in HLI. GSDMD deletion aggravated perfusion recovery and angiogenesis in vitro and in vivo. However, how GSDMD regulates angiogenesis after ischemic injury remains unclear. We then found that GSDMD-mediated pyroptosis exerted the angiogenic capacity in macrophages rather than endothelial cells after HLI. GSDMD deletion led to a lower level of CCL11 in mice serum. GSDMD knockdown in macrophages downregulated the expression and decreased the releasing level of CCL11. Furthermore, recombinant CCL11 improved endothelial functions and angiogenesis, which was attenuated by CCL11 antibody. Taken together, these results demonstrate that GSDMD promotes angiogenesis by releasing CCL11, thereby improving blood flow perfusion recovery after hindlimb ischemic injury. Therefore, CCL11 may be a novel target for prevention and treatment of vascular ischemic diseases.
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BACKGROUND: For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood. METHODS: Gastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT. RESULTS: Between 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection (p-value = 0.001), higher ypT stage (p-value = 0.004), ypN + (p-value = 0.008), and non-response ( p-value = 0.012). CONCLUSION: A decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results.
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Gastrectomía , Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Masculino , Femenino , Países Bajos , Persona de Mediana Edad , Anciano de 80 o más Años , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Privación de Tratamiento/estadística & datos numéricosRESUMEN
Objective: Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer. Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer. Results: Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0). Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.
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Background: Angio-based index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) have been developed, however, the differences between baseline and hyperemic data and their effects on their computation have not yet been discussed. This study aimed to compare the diagnostic performance of a novel method for calculating IMR and FFR from coronary angiography under baseline and hyperemic conditions. Methods: We performed a retrospective study to investigate the diagnostic performance of angiography-derived IMR (AccuIMR) and FFR (AccuFFRangio) computed from the hyperemic condition (AccuIMRhyp, AccuFFRangiohyp) and baseline condition (AccuIMRbase, AccuFFRangiobase) in 101 consecutive patients with chronic coronary syndrome (CCS) who underwent measurements of IMR and FFR at a single center, using wire-based IMR and FFR as the reference standard. Results: AccuIMRhyp showed much better correlation with IMR than AccuIMRbase (r=0.77 vs. 0.47, P<0.001). The diagnostic accuracy and area under the curve (AUC) for identifying significant microvascular dysfunction was higher for AccuIMRhyp than AccuIMRbase [92.1% (95% CI: 85.0-96.5%) vs. 83.2% (95% CI: 74.4-89.9%), P=0.012; 0.942 (95% CI: 0.877-0.979) vs. 0.815 (95% CI: 0.726-0.886), P=0.003]. The computed AccuFFRangio showed good correlations with FFR and good diagnostic performance under both hyperemic and baseline conditions [r=0.68 vs. 0.68, P>0.99; diagnostic accuracy =95.9% (95% CI: 89.8-98.9%) vs. 94.9% (95% CI: 88.4-98.3%), P=0.728; AUC =0.989 (95% CI: 0.942-1.000) vs. 0.973 (95% CI: 0.919-0.995), P=0.381]. The net reclassification index (NRI) demonstrated that hyperemic group had improved reclassification ability compared to the baseline group in identification of IMR >25 (NRI =0.20, P<0.001) and FFR ≤0.8 (NRI =0.11, P<0.001). Conclusions: By comparing the calculated angio-derived IMR and FFR under the baseline and hyperemic conditions, this study demonstrates that AccuIMR calculation is more accurate using the hyperemic condition, while AccuFFRangio calculation is accurate under both conditions.
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BACKGROUND: The effectiveness of immunotherapy has been validated in multiple cancers. However, not all patients benefit from immunotherapy, and its objective response rate is less than 30% in some cancers, so it is of great importance to find a pan-cancer biomarker that can effectively predict immunotherapy response. METHODS: Fifteen immunotherapy datasets were retrospectively analyzed to determine pan-cancer biomarkers to predict immunotherapy response. A total of 348 patients with metastatic urothelial carcinoma (mUC) who received anti-PD-L1 immunotherapy from the dataset of IMvigor210 trial were included in the primary analysis. In addition, 12 public immunotherapy datasets of different cancers and two datasets of gastrointestinal cancer patients who received anti-PD-1 or anti-PD-L1 immunotherapy between August 2015 and May 2019 at Peking University Cancer Hospital (PUCH) were analyzed as validation cohorts. RESULTS: The expression of CXCL9, IFNG, and GBP5 was independently associated with the response to anti-PD-L1 immunotherapy in patients with mUC. The ability of the expression panel of CXCL9, IFNG, and GBP5 to predict immunotherapy response was validated in immunotherapy datasets of different cancers. CONCLUSION: The expression panel of CXCL9, IFNG, and GBP5 can potentially be a pan-cancer biomarker for predicting immunotherapy response.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) and obesity are metabolic diseases characterized by high economic and health burdens. A combination of sodium glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) and glucagon-like peptide-1 receptor agonist (GLP1-RA) exenatide (ExQW) has not been explored as a treatment strategy for T2DM patients with obesity. Therefore, this retrospective analysis compared the efficacy and safety of dapagliflozin (DAPA) combined with GLP1-RAs Exenatide (ExQW) and dapagliflozin alone in the treatment of 125 T2DM patients with obesity. METHODS: This study is a retrospective study. From May 2018 to December 2019, 62 T2DM patients with obesity were treated with DAPA + ExQW, labeled DAPA + ExQW group. From December 2019 to December 2020, 63 patients with T2DM and obesity were treated with DAPA + placebo, labeled the DAPA + placebo group. DAPA + ExQW group received DAPA at a dose of 10 mg/day plus ExQW at 2 mg/week and DAPA + placebo group was administered with DAPA at a dose of 10 mg/day plus a placebo. The primary outcome for the present study was change in HbA1c (%) at different treatment points relative to the baseline. The secondary outcomes included changes in fasting plasma glucose (FPG, mmol/L), systolic blood pressure (SBP, mm/Hg) and body weight (BW, kg). Study outcomes were evaluated at 0, 4, 8, 12, 24, and 52 weeks after initial treatment. All P values were two-sided, with a P value less than 0.05 indicating statistical significance. RESULTS: A total of 125 patients completed the present study (62 in the DAPA + ExQW group and 63 in the DAPA group). Patients in the DAPA group showed a significant decrease in the level of HbA1c during the first 4 weeks, but the HbA1c level in this group remained stable for the remaining 48 weeks. Similar results were observed for other variables such as FPG, SBP, and BW. Patients who received a combination of DAPA and ExQW exhibited a continuous decline in the evaluated variables. The decrease in all the variables was greater in the DAPA + ExQW group than that in the DAPA group. CONCLUSIONS: A combination of DAPA and ExQW exerts a synergistic effect in the treatment of T2DM patients with obesity. However, the potential synergistic mechanism of this combination should be studied further.
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BACKGROUND: Objective: The aim of this study was to analyze the role of blood Glucagon like peptide-1 (GLP-1), insulin-like growth element-1 (IGF-1), and type 2 diabetes mellitus (T2DM) in coronary heart disease (CHD). METHOD: In this study, the clinical data of T2DM patients (n=203) admitted to Baoding Second Hospital from June 2020 to June 2021 were retrospectively analyzed. The patients included 65 T2DM patients without CHD who were assigned to the T2DM group and 138 T2DM patients with a CHD and T2DM comorbidity assigned to the CHD group. The baseline demographic characteristics and laboratory indexes of the two groups were explored, and the relationship between expression profiles of GLP-1 and IGF-1 levels and T2DM complicated by CHD was evaluated. The patients in the CHD group were sub-classified by the SYNTAX score system according to the results of coronary angiography. The three groups included a low-risk group with 52 cases, medium-risk group with 45 cases, and high-risk group with 41 cases. The relationship between GLP-1 and IGF-1 levels and the risk level of T2DM complicated by CHD was evaluated. RESULTS: Significant differences in age, smoking history, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), fasting blood glucose, GLP-1, and IGF-1 were observed between the two groups. Multivariate analysis revealed that smoking history, LDL-C, GLP-1, and IGF-1 were risk factors for CHD. Spearman correlation analysis showed a positive correlation between GLP-1 level and the occurrence of T2DM complicated by CHD, whereas IGF1 level was negatively correlated with the occurrence of T2DM complicated by CHD. GLP-1 and IGF-1 levels showed significant differences between risk groups. The GLP-1 level in the high-risk group was higher than that in the low- and medium-risk groups whereas IGF-1 level was lower in the high-risk group relative to the other two groups. CONCLUSION: Blood GLP-1 and IGF1 levels were associated with occurrence of T2DM complicated by CHD. Elevated level of blood GLP-1 was positively correlated with high risk of T2DM complicated by CHD whereas a lower blood IGF1 level was positively correlated with risk of T2DM complicated by CHD.
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Autophagy is critically involved in myocardial ischemia-reperfusion (I/R). Autophagy inhibition exacerbates myocardial I/R injury. Few effective agents target autophagy to prevent myocardial I/R injury. Effective drugs that promote autophagy in myocardial I/R warrant further investigation. Galangin (Gal) enhances autophagy and alleviates I/R injury. Here we conducted both in vivo and in vitro experiments to observe the changes in autophagy after galangin treatment and investigated the cardioprotective effects of galangin on myocardial I/R. METHODS: After 45-min occlusion of the left anterior descending coronary artery, myocardial I/R was induced by slipknot release. One day before surgery and immediately after surgery, the mice were injected intraperitoneally with the same volume of saline or Gal. The effects of Gal were evaluated using echocardiography, 2,3,5-triphenyltetrazolium chloride staining (TTC staining), western blotting, and transmission electron microscopy. Primary cardiomyocytes and bone marrow-derived macrophages were extracted in vitro to measure the cardioprotective effects of Gal. RESULTS: Compared with the saline-treated group, Gal significantly improved cardiac function and limited infarct enlargement after myocardial I/R. In vivo and in vitro studies demonstrated that Gal treatment promoted autophagy during myocardial I/R. The anti-inflammatory effects of Gal were validated in bone marrow-derived macrophages. These results strongly suggest that Gal treatment can attenuate myocardial I/R injury. CONCLUSION: Our data demonstrated that Gal could improve left ventricular ejection fraction and reduce infarct size after myocardial I/R by promoting autophagy and inhibiting inflammation.
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Daño por Reperfusión Miocárdica , Ratones , Animales , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Volumen Sistólico , Función Ventricular Izquierda , Miocitos Cardíacos , Autofagia , InfartoRESUMEN
BACKGROUND: There is a paucity of data comparing functional difference between active jailed balloon technique (A-JBT) and conventional jailed balloon technique (C-JBT) in treating non-left main coronary bifurcation lesions (CBLs). METHODS: In this retrospective cohort study, we consecutively enrolled 232 patients with non-left main CBLs who underwent percutaneous coronary intervention (PCI) using JBTs between January 2018 and March 2019. Among them, 191 patients entered the final analysis with 12-months angiographic follow-up. We stratified patients into A-JBT group (130 patients) and C-JBT group (61 patients). The functional analysis by Murray law-based quantitative flow ratio (µQFR) and Seattleanginaquestionnaire (SAQ) were performed to compare the two techniques. RESULTS: Compared with C-JBT group, A-JBT group observed a lower abrupt (0.8% vs. 11.1%, p = 0.002) and final SB occlusion (0 vs. 7.9%, p = 0.005). Meanwhile, A-JBT group had a significantly higher µQFR of side branch (SB) both post-PCI and 12-months follow-up (median [interquartile range (IQR)]: 0.91 (0.86-0.96) vs. 0.82 (0.69-0.92), p < 0.001; median [IQR]: 0.95 (0.89-0.98) vs. 0.85 (0.74-0.93), p < 0.001) than C-JBT group. Besides, A-JBT group gained a µQFR improvement at follow-up period compared with post-PCI data (median [IQR]: 0.95 [0.89-0.98] vs. 0.91[0.86-0.96] of SB, p < 0.001) and a higher SAQ scores at 12-months follow-up compared with C-JBT group (p < 0.001). CONCLUSIONS: Compared with C-JBT, A-JBT provided excellent SB protection during MV stenting and improved the SB functional blood flow as well as the angina relief even after 12 months.
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Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Angioplastia Coronaria con Balón/métodos , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
Purpose: As the human body's largest organ exposed to the external environment, the skin suffers from internal and external aging factors, leading to wrinkles, loss of elasticity, sagging, and rough appearance. However, little is known of the characteristics of skin aging of different body parts in Chinese women. Here, we study the signs of extrinsic skin aging in different body parts to identify the knowledge map of manifestations of aging in Chinese women. Patients and Methods: Wrinkle and texture phenotypes and collagen samples from the face, neck, hands, and arms of 326 Chinese women were collected. The correlations between phenotypes and ages and the differences in phenotypes by age were evaluated. Results: The wrinkle and texture phenotypes around the eyes and mouth and of the hands were strongly correlated with age. Ages 32 and 58 showed the largest number of differentially changed aging phenotypes. The number of aging phenotypes increased sharply between the ages of 24 and 30, suggesting that the skin was undergoing rapid aging. Eye aging was the most rapidly changing phenotype between 19 and 30 years old. Wrinkles at the corner of the eyes showed a significant difference in the older group, suggesting an early onset and long-term effects. Conclusion: This is the first study to be performed on the characteristics of skin aging among Chinese women that takes account of multiple areas of the body. It was found that 24 years old was the time point at which the skin begins to age in Chinese women. This provides important clues for aging-related research and personalized skin care.
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INTRODUCTION: Lung cancer (LC) is among the most prevalent malignancies worldwide, with extremely high morbidity and mortality rates. Mounting evidence has suggested that the abnormally expressed long noncoding RNA (lncRNA) in lung cancer tissues may play vital roles in tumor progression. In the present research, we aimed to examine the functions and underlying mechanism of linc01833 in lung adenocarcinoma (LUAD). METHODS: qRT-PCR was employed to determine transfection efficiency. CCK-8, transwell invasion assay, Western blotting analysis and qRT-PCR were used to detect proliferation as well as migration of different LUAD cell lines, and were also applied to determine the changes during epithelial-mesenchymal transformation (EMT). Afterwards, bioinformatics and dual-luciferase reporter assay were utilized to explore and to identify the potential corresponding targets of linc01833 and miR-519e-3p. RESULTS: Linc01833 OE can significantly improve proliferation as well as invasion ability of LC cells and promote the EMT process. Dual-luciferase reporter assay demonstrated that linc01833 could directly bind to miR-519e-3p, thereby inhibiting its expression. Further experiments showed that S100A4 was a direct target of miR-519e-3p. Rescue assay demonstrated that linc01833 acted on the miR-519e-3p/S100A4 axis. CONCLUSION: We verified the mechanism of linc01833 in promoting infiltration and metastasis in LUAD. To be specific, linc01833 can function as a competitive endogenous RNA (ceRNA) to adsorb miR-519e-3p through a sponge and regulate S100A4 in lung cancer, thereby being involved in LUAD progression. Collectively, our research provides new insights towards the in-depth understanding of LC progression mechanisms.
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INTRODUCTION: CD27 is a co-stimulatory immune checkpoint molecule in the tumor necrosis factor receptor superfamily. CD27 regulates the generation and maintenance of T cell immunity by binding to CD70 and regulating B-cell activation and immunoglobulin synthesis. MATERIALS AND METHODS: CD27 and CD70 expression were assessed in esophageal squamous cell carcinoma (ESCC) compared to normal tissue samples in the GSE53625 dataset of 179 paired cases and in 153 Chinese cases using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The correlation was also investigated between CD27 and CD70 expression and immune-related pathways, including CD8+ T cell recruitment, function, and other inhibitory immune checkpoints. RESULTS: Levels of both CD27 and CD70 expression were down-regulated in ESCC compared to the paired normal tissues. CD27 and CD70 expression was mainly present in lymphocytes surrounding and infiltrating the tumor lesions but rarely expressed in tumor cells. Lost expression of CD27 and CD70 was associated with clinicopathological features, including depth of tumor invasion and better patient survival. Furthermore, CD27 expression was significantly associated with levels of CD8A, GZMB, IFNG, the CD8+ T cell recruitment-associated chemokines (CXCL9, CXCL10, and CXCL11), and CD8 receptors (CCR5, CXCR6, and CXCR3), while CD70 expression was inversely associated with levels of immunosuppressive checkpoints (PD-L1, PD-L2, and HHLA2). CONCLUSION: Detection of CD70/CD27 expression could be further verified as a biomarker for ESCC early detection and prognosis prediction.
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The secure full-duplex (FD) simultaneous wireless information and power transfer (SWIPT) system and non-orthogonal multiple access (NOMA) have been deemed two promising technologies for the next generation of wireless communication. In this paper, the network is combined with device-to-device (D2D) and a practical bounded channel state information (CSI) estimation scheme. A system total transmit power minimization problem is studied and formulated as a multi-objective optimization (MOO) problem via the weighted Tchebycheff approach. A set of linear matrix inequalities (LMI) is used to transform the non-convex form of constraints into the convex form. Considering the imperfect CSI of the potential eavesdropper for robust power allocation, a bounded transmission beamforming vector design along with artificial noise (AN) is used, while satisfying the requirements from the secrecy rates as well as the energy harvesting (EH) task. Numerical simulation results validate the convergence performance and the trade-off between the uplink (UL) and downlink (DL) data transmit power. It is also shown that by FD and NOMA, the performance of the proposed algorithm is higher than that of half-duplex (HD) and orthogonal multiple access (OMA).
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BACKGROUND: Most surgeons now accept lymphadenectomy as an essential feature of the operative treatment of esophageal squamous cell carcinoma. Three-field and two-field lymphadenectomy are two of the most popular excision scopes among surgeons. Over recent years, researchers have performed a range of comparative studies regarding these techniques, although the conclusions remain inconsistent. METHOD: We systematically retrieved the records of PubMed, Embase, The Cochrane Library, and ClinicalTrials.gov until October 2019 and performed preliminary and full-text screening of the articles. We used the NOS scale to evaluate the quality of the enrolled studies, with only medium- and high-quality studies included. Review Manager 5.3 and Stata15 were used for the meta-analysis. RESULTS: A total of eight studies involving 1676 patients were included in the meta-analysis. The results showed that for esophageal squamous cell carcinoma using with two-field and three-field lymphadenectomy, although three-field lymphadenectomy led to the gaining of a higher number of lymph nodes, there were no significant differences between the two in terms of the number of positive lymph nodes and overall survival. Three-field lymphadenectomy also caused higher levels of intraoperative blood loss and higher morbidity of the anastomotic fistula. No significant differences in operation time, recurrent laryngeal nerve injury, pneumonia, chylothorax, anastomotic stenosis, ileus, cervical nodal recurrence and hospital mortality were observed. CONCLUSIONS: According to our meta-analysis, two-field lymphadenectomy is recommended as a first-choice surgical treatment for esophageal squamous cell carcinoma. However, since the results showed a risk of bias, they should be treated with caution.
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Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Escisión del Ganglio Linfático/estadística & datos numéricos , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/mortalidad , Humanos , Escisión del Ganglio Linfático/métodos , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Prostate cancer (PCa) is the most commonly diagnosed solid-organ cancer in males. The PSA testing may cause overdiagnosis and overtreatment for PCa patients. There is an urgent need for new biomarkers with greater discriminative precision for diagnosis and risk-stratification, to select for prostate biopsy and treatment of PCa. Liquid biopsy is a promising field with the potential to provide comprehensive information on the genetic landscape at diagnosis and to track genomic evolution over time in order to tailor the therapeutic choices at all stages of PCa. Exosomes, containing RNAs, DNAs and proteins, have been shown to be involved in tumour progression and a rich potential source of tumour biomarkers, especially for profiling analysis of their miRNAs content. In this review, we summarise the exosomal miRNAs in PCa diagnosis, prognosis and management, and further discuss their possible technical challenges associated with isolating PCa-specific exosomes.
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Exosomas , Biopsia Líquida , MicroARNs , Neoplasias de la Próstata , Biomarcadores de Tumor , Biopsia , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genéticaRESUMEN
BACKGROUND: Minimally invasive esophagectomy (MIE) is increasingly accepted in many countries. McKeown esophagectomy and Ivor Lewis esophagectomy are two protocols commonly used for MIE, but which one provides more benefit to the patients remains matter of controversy. METHODS: All records in PubMed, Embase, Medline, The Cochrane Library, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Chinese VIP Information till May 2019 were systematically retrieved to compare the cohort studies of McKeown esophagectomy and Ivor Lewis esophagectomy. A meta-analysis of the extracted data was performed using the Review Manager 5.3 and Stata 15 software. RESULTS: The meta-analysis included 23 cohort studies in which a total of 4,933 patients were enrolled. The results revealed that minimally invasive McKeown esophagectomy (MIME) was superior to minimally invasive Ivor Lewis esophagectomy (MILE) in hospital cost, but inferior to it in operating time, length of hospital stay, in-hospital mortality, 30-day mortality, 90-day mortality, anastomotic leakage, anastomotic leakage requiring surgery, anastomotic stenosis, recurrent laryngeal nerve (RLN) injury, chylothorax, pulmonary complications and total complications. There were no statistical differences between MIME and MILE in blood loss, detected number of lymph nodes, blood transfusion rate, R0 resection rate, re-operation rate, drainage duration, length of the stay in intensive care unit (ICU), 1-year mortality, lung infection, cardiac arrhythmia and delayed gastric emptying. CONCLUSIONS: Except for the cost, MILE is superior to MIME in several aspects, and may represent a better choice for MIE. The results of the present study should be interpreted with caution since the meta-analysis is based on nonrandom cohort studies which may have a selection bias.
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BACKGROUND: Esophagectomy combined with lymphadenectomy has been considered as the preferred treatment option for esophageal cancer (EC). However, for a long time, no consensus is reached on the optimal number and scope of lymph node dissection (LND). In particular, related research on esophageal adenocarcinoma remains lacking at present. To determine the relationship between the number of LND and the prognosis for esophageal adenocarcinoma patients, this study was conducted based on the United States Surveillance, Epidemiology and End Results (SEER) database. METHODS: Data were extracted from esophageal adenocarcinoma patients undergoing esophagectomy from 2000 to 2016 based on the SEER database. Thereafter, the enrolled patients were divided into five groups according to the number of LND, namely, 0, 1-10, 11-20, 21-30 and >30 LNDs groups. Besides, the Kaplan-Meier product method was applied in estimating the impact of LND number on the overall survival (OS) and disease-specific survival (DSS) of patients. Moreover, the Cox proportional hazard model was employed to analyze the covariates that might affect the results. RESULTS: After adjusting for age, gender, race, grade, T stage, tumor location, tumor size and number of positive lymph nodes, differences in OS and DSS were statistically significant among those five groups, and only groups receiving >20 LNDs were related to the improved OS and DSS. Also, it was discovered that, difference in OS was of statistical significance across those five groups in the <50, ≥50 years old, male, Grade I, Grade II, Grade III, T1, T2, T3, and tumor size >4 cm subgroups. CONCLUSIONS: The number of LND can serve as an independent prognostic factor for OS and DSS among esophageal adenocarcinoma patients. In addition, we recommend that esophageal adenocarcinoma patients should undergo LND to dissect at least 20 lymph nodes.
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We previously reported that microRNA-218 was frequently lost in cervical cancer and restoration of microRNA-218 increased cellular radio-sensitivity via inhibiting. Herein, we aim to investigate the effects of microRNA-218 on cellular response to mTOR inhibition. The expression of microRNA-218 and Rictor were measured by Taqman PCR and real time PCR in a panel of 15 cervical cancer tissues. MicroRNA-218 was stably overexpressed in four cervical cancer cell lines and a series of in vitro and in vivo experiments were performed to investigate cellular sensitivity to Rapamycin. In primary cultured cervical cancer cells, the expression of microRNA-218 was negatively correlated with the mRNA level of Rictor, which predicted cellular sensitivity to Rapamycin (p = 0.002, R(2) = 0.6810). In vitro, overexpression of microRNA-218 significantly reduced the level of Rictor and enhanced the growth-inhibition, cell cycle arrest, and apoptosis induced by Rapamycin. In vivo, overexpression of microRNA-218 further enhanced the suppressive effects of Rapamycin on tumor growth. In conclusion, we demonstrated that microRNA-218 could re-sensitize cervical cancer to Rapamycin through targeting Rictor. Moreover, patients with loss of microRNA-218 presented notable resistance to Rapamycin, indicating that microRNA-218 might be a valid marker for patients-stratification in future clinical trials.