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OBJECTIVE: The aim of this study was to investigate the prognostic value of baseline peripheral blood neutrophils, monocytes, and lymphocytes on locally advanced rectal cancer (LARC) patients. METHODS: Clinicopathologic data of 317 LARC patients during July 2010 and October 2016 were retrospectively gathered. X-tile software was used to acquire the optimal cutoff values of neutrophils, monocytes, and lymphocytes. Peripheral blood immune score (PBIS) system was proposed and built based on neutrophils, monocytes, and lymphocytes. The Cox model was used to analyze the associations between clinicopathological characteristics and potential outcomes. C-index was used to assess model performance. A nomogram was constructed to predict prognosis, and a calibration plot was used to verify the accuracy of the nomogram prediction model. RESULTS: Cutoff values of neutrophils, lymphocytes, and monocytes were 4.46 (× 109/L), 1.66 (× 109/L), and 0.39 (× 109/L), respectively. PBIS was related to sex (P < 0.001), tumor length (P = 0.003), and tumor thickness (P = 0.014). Multivariate Cox regression analysis revealed that PBIS (HR = 0.707, 95% CI: 0.549-0.912, P = 0.008) was an independent predictor of DFS. High PBIS (HR = 0.697, 95% CI: 0.492-0.988, P = 0.043) and high lymphocyte count (HR = 0.511, 95%CI: 0.273-0.958, P = 0.036) were favorable factors of OS. Both C-index (0.74, 95% CI: 0.549-0.912) and the calibration plot showed good prediction ability of the nomogram for DFS. CONCLUSION: PBIS, composed of baseline peripheral blood neutrophils, monocytes, and lymphocytes, is an independent predictor of the prognosis of LARC. Combination of PBIS and ypTNM stage may be a promising marker to guide adjuvant therapy after the operation.
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Neutrófilos , Neoplasias del Recto , Humanos , Linfocitos/patología , Monocitos/patología , Terapia Neoadyuvante , Neutrófilos/patología , Pronóstico , Neoplasias del Recto/patología , Estudios RetrospectivosRESUMEN
OBJECTIVES: It is not clear whether TREM-2 (the "triggering receptor expressed on myeloid cells 2") is expressed in fibroblast-like synovial cells (FLSs). In this study, we aimed to determine the expression of TREM-2 in rheumatoid arthritis (RA)-FLSs and explore whether and how TREM-2 modulates the function of RA-FLSs. METHODS: Western blot and RT-PCR were used to detect the expression of TREM-2 in RA-FLSs, siRNA and lentivirus were used to down-regulate and up-regulate the expression of TREM-2 in RA-FLSs. Then mRNA expression of IL-1ß, IL-6, and MMP-13 was determined by RT-qPCR. Protein secretion of IL-1ß, IL-6, and MMP-13 in the supernatant was determined by ELISA assay; expression of cell signal transduction molecules was determined by western blot. RESULTS: A: Relative to OA-FLSs, mRNA and protein expression levels of TREM-2 in RA-FLSs are significantly elevated. TREM-2 protein is mainly expressed in the cytoplasm of RA-FLSs; B: In RA, the expression of TREM-2 was reduced at first and then up-regulated after stimulation by TNF-α. TREM-2 also inhibited the activation of TNF-α induced of inflammation in RA-FLSs by the p38 pathway, which regulates the production of cytokines and matrix metalloproteinases. CONCLUSIONS: TREM-2 expressed in RA-FLSs and TNF-α mediated reduction of inflammatory reactions. These phenomena indicated that TREM-2 may be a potential target in the treatment of RA.
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Inflamación/prevención & control , Glicoproteínas de Membrana/fisiología , Receptores Inmunológicos/fisiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Artritis Reumatoide/tratamiento farmacológico , Células Cultivadas , Activación Enzimática , Fibroblastos/fisiología , Humanos , Sinoviocitos/fisiología , Factor de Necrosis Tumoral alfa/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/fisiologíaRESUMEN
BACKGROUND: Early postoperative small bowel obstruction (EPSBO) is a common complication following colon cancer surgery. EPSBO is associated with increased hospital stays, mortality rates, and healthcare costs. The purpose of this study was to identify risk factors for EPSBO following elective colon cancer surgery. STUDY DESIGN: We retrospectively reviewed the clinicopathological variables of 1,244 patients with colon cancer who underwent partial colectomy from January 2000 to December 2014. A multivariable logistic regression model was used to identify risk factors for EPSBO. RESULTS: The EPSBO rate was 3.5%. In multivariate analysis, preoperative bowel obstruction (OR 2.378; 95% CI 0.986-5.735, p = 0.054), weight loss >10% of body weight (OR 3.029; 95% CI 1.000-9.178, p = 0.05), albumin level (in g/L; OR 0.966; 95% CI 0.937-0.996, p = 0.024), and surgical duration (in min; OR 1.008; 95% CI 1.003-1.012, p = 0.003) were significant predictors of EPSBO. CONCLUSION: EPSBO is more likely to develop in the presence of poor systemic conditions (e.g., weight loss >10% of body weight, hypoalbuminemia, and preoperative bowel obstruction) and following operations of longer duration. These predictors may facilitate the stratification of patients at risk for EPSBO following surgery for elective colon cancer.
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Colectomía , Neoplasias del Colon/cirugía , Procedimientos Quirúrgicos Electivos , Obstrucción Intestinal/etiología , Complicaciones Posoperatorias/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Intestino Delgado , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) block is an adjunct therapy to provide effective postoperative analgesia in abdominal surgical procedures. Dexamethasone is a supplement agent that can improve the efficacy of local anesthesia. However, information about its additive effect is limited. This study aimed to compare the analgesic efficiency using ultrasound-guided TAP block with and without perineural dexamethasone for patients who underwent laparoscopic cholecystectomy. METHODS: Sixty patients who underwent laparoscopic cholecystectomy were randomly divided into three groups: group I, controls; group II, TAP; and group III, TAP+perineural dexamethasone supplement. The requirement of additional analgesia and the first-time request of rescue-analgesia were recorded after operation and the numerical rating scale was evaluated at specific intervals. RESULTS: Compared to group I, the first-time requirement of rescue-analgesia in groups II and III was significantly delayed (403.0+/-230.9, 436.0+/-225.3 vs 152.3+/-124.7, P<0.01). Compared with those in group I, patients in groups II and III were associated with lower numerical rating scale pain scores (P<0.01) and less postoperative analgesic consumption (P<0.01). There was no significant difference in the variables mentioned above between groups II and III (P>0.05). CONCLUSION: Perineural dexamethasone has no additive/synergistic effect with subcostal TAP block on analgesic efficacy for the patients undergoing laparoscopic cholecystectomy.
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Músculos Abdominales/inervación , Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Colecistectomía Laparoscópica , Dexametasona/administración & dosificación , Glucocorticoides/administración & dosificación , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Ultrasonografía Intervencional , Adulto , Amidas/efectos adversos , Anestésicos Locales/efectos adversos , China , Colecistectomía Laparoscópica/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Dimensión del Dolor , Umbral del Dolor/efectos de los fármacos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/fisiopatología , Ropivacaína , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Traditionally, conventional intersphincteric resection requires a combined abdominal and perineal approach and a handsewn coloanal anastomosis procedure, which is difficult to accomplish via the perineal approach. A completely abdominal approach partial intersphincteric resection (APISR) with laparoscopy can simplify the anastomosis procedure. This study evaluated the intermediate-term oncological and functional results of laparoscopic versus open APISR for low rectal cancer. METHODS: A total of 137 consecutive patients with low rectal cancer who underwent APISR from January 2006 to August 2013 were retrospectively evaluated. Patient groups were classified into as open surgery (OP, n = 48) group and laparoscopy (LAP, n = 89). The primary endpoint was 3-year disease-free survival and the Wexner score for anal function. RESULTS: The LAP group had longer operating time, less intraoperative blood loss, and shorter hospital stay after surgery compared with the OP group. Median follow-up was 32.3 months. The local recurrence rates were similar in the two groups (LAP 3.2% vs. OP 6.1%; P = 0.652). The combined 3-year disease-free survival rate was 83.2% in the LAP group and 83.8% in the OP group (P = 0.857). Wexner scores were similar in the two groups (LAP 2.9 ± 4.5 vs. OP 3.1 ± 5.0). In the LAP group, 89.7% of patients had good continence compared with 91.4% in the OP group (P = 0.311). CONCLUSIONS: Laparoscopic APISR can be performed safely and offers similar intermediate-term oncological and functional outcome compared with the open procedure. The oncological adequacy requires long-term follow-up data.
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Adenocarcinoma/cirugía , Canal Anal/cirugía , Anastomosis Quirúrgica/métodos , Laparoscopía/métodos , Complicaciones Posoperatorias , Neoplasias del Recto/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Canal Anal/patología , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: The aim of this study is to establish a prediction scoring system for inferior mesenteric artery (IMA) lymph node metastasis and to assess the prognostic impact of dissection of positive IMA node on patients with stage III rectal cancer. METHODS: A retrospective study was performed in 264 patients with stage III rectal cancer undergoing curative surgery. Clinicopathological, survival, and recurrence data were compared between 29 patients with positive IMA nodes and 235 patients with negative IMA nodes. Clinicopathological data which were found to be significantly associated with IMA nodal status were incorporated into a scoring system. RESULTS: In the training samples, tumor differentiation and preoperative serum CEA were significant predictors of IMA node metastasis in multivariate analysis, which were incorporated into a scoring system. Using receiver operating characteristic curve analysis, we determined a cutoff value of 46.5 for scores, at which the system's sensitivity was 86 % and specificity 61 %. When applied to testing sample, the sensitivity was 80 % and specificity 60 %. Survival analysis showed that 5-year disease-free survival rate (5-DFS) and 5-year overall survival (5-OS) in the positive IMA node group (24.4 and 27.6 %, respectively) were significantly lower than in the negative IMA node group (61.8 and 71.3 %, respectively) (P < 0.001). Furthermore, multivariate analysis indicated that IMA lymph node metastasis was an unfavorable independent prognostic factor for 5-DFS and 5-OS. CONCLUSIONS: IMA lymph node metastasis is an independent poor prognostic factor for stage III rectal cancer. The prediction scoring system for IMA node metastasis would be beneficial in determining the appropriate level of IMA ligation.
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Ganglios Linfáticos/patología , Neoplasias del Recto/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Antígeno Carcinoembrionario/sangre , Carcinoma de Células en Anillo de Sello/mortalidad , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/cirugía , Femenino , Humanos , Ligadura , Metástasis Linfática , Masculino , Arteria Mesentérica Inferior/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Curva ROC , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Recurrencia , Análisis de Regresión , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Rectovaginal fistula (RVF) is an abnormal channel formed by epithelial tissue between the anterior wall of the rectum and the posterior wall of the vagina, which manifests as vaginal gassing and defecation. It is one of the common complications of female pelvic surgeries. With the increased number of proctectomies for rectal cancer, the number of postoperative rectovaginal fistulas also increases. Once RVF occurs, the failure rate is still high with various treatments available. RVF causes great suffering to women and is still a major problem in treatment. Therefore, it is significant for female rectal cancer patients to prevent RVF after rectal cancer surgery. In this study, we introduce a new method to prevent RVF during rectal cancer radical operation. METHODS: In this randomized controlled trial (RCT), all operations are performed according to the principle of total mesorectal excision (TME) radical resection in rectal cancer surgery. All eligible participants will be divided into two groups: the experimental group and the control group. Experimental group: the anterior rectal wall of about 1 cm distal to the anastomosis was dislocated. Before the anastomosis of the rectal end, a fat flap (usually left side) containing the ovarian vascular pedicle was dislocated, measured by 10-15 cm in length and 2 cm in width. The fat flap containing the ovarian vascular pedicle was packed and fixed anterior to the anastomotic stoma with fibrin glue. CONTROL GROUP: surgery will be carried out in accordance with the TME principle. Participants will be compared on several variables, including the incidence of RVF after operation (primary outcomes), the occurrence time of postoperative RVF, the occurrence time of RVF after stoma closure, and other postoperative complications, such as anastomotic leakage, chylous leakage, and intestinal obstruction (secondary outcomes). The follow-up data collection will be conducted according to the follow-up time point, and the baseline data will also be collected for follow-up analysis. By comparing the incidence of rectovaginal leakage between the experimental group and the control group, we aim to explore the feasibility of this method for the prevention of postoperative RVF. DISCUSSION: This RCT will explore the feasibility of packing with a laparoscopic dislocated fat flap containing an ovarian vascular pedicle anterior to the anastomotic stoma after rectal cancer surgery to prevent RVF. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) registration ChiCTR2000031449. Registered on June 26, 2019. All items of the WHO Trial registration data set can be found within the protocol.
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Laparoscopía , Neoplasias del Recto , Femenino , Humanos , Recto/cirugía , Fístula Rectovaginal/etiología , Fístula Rectovaginal/prevención & control , Fístula Rectovaginal/cirugía , Neoplasias del Recto/cirugía , Anastomosis Quirúrgica/efectos adversos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Fuga Anastomótica/etiología , Fuga Anastomótica/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. METHODS: Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. RESULTS: Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P <0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P <0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P <0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. CONCLUSIONS: Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.
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Adenocarcinoma , Biomarcadores de Tumor , Antígeno CA-19-9 , Antígeno Carcinoembrionario , Neoplasias del Colon , Humanos , Masculino , Neoplasias del Colon/cirugía , Neoplasias del Colon/mortalidad , Neoplasias del Colon/sangre , Neoplasias del Colon/patología , Femenino , Persona de Mediana Edad , Pronóstico , Antígeno Carcinoembrionario/sangre , Biomarcadores de Tumor/sangre , Adenocarcinoma/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/sangre , Adenocarcinoma/patología , Anciano , Antígeno CA-19-9/sangre , Estudios Retrospectivos , Colectomía , Recurrencia Local de Neoplasia/sangre , Adulto , Periodo Preoperatorio , Tasa de Supervivencia/tendencias , Periodo Posoperatorio , Cuidados Preoperatorios/métodos , Anciano de 80 o más AñosRESUMEN
This paper proposes a Human Intelligence (HI)-based Computational Intelligence (CI) and Artificial Intelligence (AI) Fuzzy Markup Language (CI&AI-FML) Metaverse as an educational environment for co-learning of students and machines. The HI-based CI&AI-FML Metaverse is based on the spirit of the Heart Sutra that equips the environment with teaching principles and cognitive intelligence of ancient words of wisdom. There are four stages of the Metaverse: preparation and collection of learning data, data preprocessing, data analysis, and data evaluation. During the data preparation stage, the domain experts construct a learning dictionary with fuzzy concept sets describing different terms and concepts related to the course domains. Then, the students and teachers use the developed CI&AI-FML learning tools to interact with machines and learn together. Once the teachers prepare relevant material, students provide their inputs/texts representing their levels of understanding of the learned concepts. A Natural Language Processing (NLP) tool, Chinese Knowledge Information Processing (CKIP), is used to process data/text generated by students. A focus is put on speech tagging, word sense disambiguation, and named entity recognition. Following that, the quantitative and qualitative data analysis is performed. Finally, the students' learning progress, measured using progress metrics, is evaluated and analyzed. The experimental results reveal that the proposed HI-based CI&AI-FML Metaverse can foster students' motivation to learn and improve their performance. It has been shown in the case of young students studying Software Engineering and learning English.
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Calorie restriction (CR) and intermittent fasting (IF) without malnutrition reduce the risk of cancer development. Separately, CR and IF can also lead to gut microbiota remodelling. However, whether the gut microbiota has a role in the antitumour effect related to CR or IF is still unknown. Here we show that CR, but not IF, protects against subcutaneous MC38 tumour formation through a mechanism that is dependent on the gut microbiota in female mice. After CR, we identify enrichment of Bifidobacterium through 16S rRNA sequencing of the gut microbiome. Moreover, Bifidobacterium bifidum administration is sufficient to rescue the antitumour effect of CR in microbiota-depleted mice. Mechanistically, B. bifidum mediates the CR-induced antitumour effect through acetate production and this effect is also dependent on the accumulation of interferon-γ+CD8+ T cells in the tumour microenvironment. Our results demonstrate that CR can modulate the gut taxonomic composition, which should be of oncological significance in tumour growth kinetics and cancer immunosurveillance.
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Restricción Calórica , Microbioma Gastrointestinal , Femenino , Animales , Ratones , Linfocitos T CD8-positivos , ARN Ribosómico 16S/genéticaRESUMEN
Antimicrobial peptides (AMPs) are considered as potential substitutes of antibiotics in the field of new anti-infective drug design. There have been several machine learning algorithms and web servers in identifying AMPs and their functional activities. However, there is still room for improvement in prediction algorithms and feature extraction methods. The reduced amino acid (RAA) alphabet effectively solved the problems of simplifying protein complexity and recognizing the structure conservative region. This article goes into details about evaluating the performances of more than 5,000 amino acid reduced descriptors generated from 74 types of amino acid reduced alphabet in the first stage and the second stage to construct an excellent two-stage classifier, Identification of Antimicrobial Peptides by Reduced Amino Acid Cluster (iAMP-RAAC), for identifying AMPs and their functional activities, respectively. The results show that the first stage AMP classifier is able to achieve the accuracy of 97.21 and 97.11% for the training data set and independent test dataset. In the second stage, our classifier still shows good performance. At least three of the four metrics, sensitivity (SN), specificity (SP), accuracy (ACC), and Matthews correlation coefficient (MCC), exceed the calculation results in the literature. Further, the ANOVA with incremental feature selection (IFS) is used for feature selection to further improve prediction performance. The prediction performance is further improved after the feature selection of each stage. At last, a user-friendly web server, iAMP-RAAC, is established at http://bioinfor.imu.edu. cn/iampraac.
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BACKGROUND: Flap transplantation is often needed for soft tissue defects of the fingers that cannot be closed directly. Sensory reconstruction of the fingers is important for patients to recover feelings. In this study, we report clinical outcomes of using free neurovascular transverse wrist crease flap for repairing finger defects from multiple centers. METHODS: This case series includes 72 consecutive patients with finger defects between June 2013 and June 2016 from multiple centers. A neurovascular transverse free radial artery superficial palmar branch flap, named transverse wrist crease flap, was designed to reconstruct soft tissue defects of the fingers with microvascular anastomosis. When there were soft tissue defects of the fingers with digital nerve defect, end-to-end neurorrhaphy between the median palmar cutaneous branch and the digital nerves was also performed. The donor incision was sutured directly. All the patients were followed-up for more than 24 months. RESULTS: The soft tissue defects of the fingers were all completely covered with this free neurovascular transverse wrist crease flap, and the flaps in 71 patients survived completely without ischemia. Vascular crisis appeared in one case, and the wound healed gradually after changing wound dressing for nearly 1 month. Slight infections of wounds appeared in eight cases. There were no complications in the donor site, like infection and poor wound healing. At the last follow-up, the mean static two-point discrimination was 9.6 ± 2.4 mm on the injured finger and 4.5 ± 0.8 on the contralateral corresponding finger. The motion range of the distal interphalangeal joint and proximal interphalangeal joint on the injured finger were 72.5 ± 23.3% and 78.7 ± 32.5% of the contralateral corresponding finger, respectively. Patient self-evaluations were good in 53 cases and fair in 19 cases. CONCLUSIONS: The results indicate that the free neurovascular transverse wrist crease flap is a good choice for repairing soft tissue defects of the fingers. LEVEL OF EVIDENCE: Therapeutic IV.
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Traumatismos de los Dedos/cirugía , Traumatismos de los Tejidos Blandos/cirugía , Colgajos Quirúrgicos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Muñeca/cirugíaRESUMEN
Long noncoding RNAs (lncRNAs) have been reported to serve a key role in a variety of cardiovascular diseases, including in cardiac fibrosis. The present study aimed to investigate the biological role and underlying mechanisms of the induction of cardiac fibroblasts by the lncRNA, RNA component of mitochondrial RNA processing endoribonuclease (RMRP). The results demonstrated that RMRP expression was upregulated in the presence of cardiac fibrosis in an abdominal aortic bandingtreated rat model. Treatment with angiotensin II increased RMRP expression in cardiac fibroblasts, while the knockdown of RMRP by smallinterfering RNA inhibited cardiac fibroblast proliferation, differentiation and collagen accumulation. To further investigate the underlying mechanisms of this interaction, microRNA (miR)613 was predicted to be a target miR of RMRP and sequence alignment, luciferase activity and MS2 RNA immunoprecipitation were performed to detect the interaction between RMRP and miR613. The results suggested that RMRP negatively regulated miR613 in cardiac fibroblasts. Furthermore, miR613 was indicated to mediate the promoting effect of RMRP on cardiac fibroblast activation. The current study suggested that RMRP promoted cardiac fibroblast activation by acting as a competing endogenous RNA for miR613. Therefore, RMRP may be a novel target for the prevention or treatment of cardiac ï¬brosis.
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Fibroblastos/metabolismo , MicroARNs/genética , Miocardio/metabolismo , ARN Largo no Codificante/genética , Regulación hacia Arriba , Animales , Células Cultivadas , Endorribonucleasas/genética , Fibroblastos/citología , Fibroblastos/patología , Fibrosis , Masculino , Miocardio/citología , Miocardio/patología , Ratas Sprague-DawleyRESUMEN
It has been suggested that poly(ADP-ribose) polymerase-l (PARP-l) plays an important role in DNA repair, cell death and proliferation, as well as in the stabilization of the genome. Pharmacological inhibition or genetic ablation of PARP-1 had a beneficial outcome in cancer chemotherapy since the cancer cells lacked PARP-1 and were sensitive to chemotherapeutic DNA damage. As a novel potent specific inhibitor of PARP-l, PJ34 has been reported to enhance chemotherapeutic effects in certain types of tumors. In a previous study, we found that PARP-1 expression was significantly increased in human hepatocellular carcinoma (HCC) compared to its surrounding liver tissue. This study investigated whether or not the inhibition of PARP-1 activity by PJ34 produces suppressive effects on human liver cancer cells and sensitizes the tumor cells to chemotherapeutic agents. We conclude that PJ34 significantly suppresses HepG2 cell growth in a dose-dependent manner, and inhibits HepG2 cell-derived tumor growth in nude mice. The suppressive effects of PJ34 are associated with increased cell apoptosis. Furthermore, PJ34 enhances suppressive effects of cisplatin in HepG2 cells. These results suggest that PJ34 may be developed into an effective agent for the treatment of human HCC.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Cisplatino/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Hepáticas/patología , Fenantrenos/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Sinergismo Farmacológico , Quimioterapia Combinada , Hepatocitos/efectos de los fármacos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/metabolismoRESUMEN
Postoperative cognitive dysfunction (POCD) is a severe complication characterized by cognitive dysfunction following anesthesia and surgery. The aim of the present study was to investigate the effects of ßsite amyloid precursor protein cleavage enzyme 1 (BACE1) gene silencing on isoflurane anesthesiainduced POCD in immature rats via the phosphatidylinositol3kinase (PI3K)/protein kinase B (Akt) signaling pathway. Rat models were established and then transfected with BACE1 small interfering RNA and wortmannin (an inhibitor of PI3K). Blood gas analysis was performed, and a series of behavioral experiments were conducted to evaluate the cognitive function, learning ability and locomotor activity of rats. Reverse transcription quantitative polymerase chain reaction and western blot analysis were employed to determine the mRNA and protein expression of the associated genes. An ELISA was used to detect the inflammatory indicators and the content of amyloid precursor protein (APP) and amyloidß (Aß). Apoptosis of the hippocampal CA1 region was observed by terminal deoxynucleotidyl transferase dUTP nickend labeling staining. Initially, it was revealed that the percentage of stagnation time in rats was increased by BACE1 gene silencing; the escape latency and swimming distance were markedly reduced from the 4th to the 6th day, the time the rats spent in first passing the target area was shortened, and the times of passing the target area were increased by BACE1 gene silencing, demonstrating that BACE1 gene silencing enhanced the spatial memory ability of rats. Additionally, it was determined that silencing BACE1 improved the pathological state induced by isoflurane anesthesia in immature rats, and attenuated the inflammatory response and the levels of APP and Aß in hippocampal tissues. Furthermore, it was suggested that silencing BACE1 may have promoted the activation of the PI3K/Akt signaling pathway, thereby inhibiting the apoptosis of the hippocampal CA1 region. Taken together, these results indicated that BACE1 gene silencing may improve isoflurane anesthesiainduced POCD in immature rats by activating the PI3K/Akt signaling pathway and inhibiting the Aß generated by APP.
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Secretasas de la Proteína Precursora del Amiloide/genética , Anestésicos por Inhalación/efectos adversos , Ácido Aspártico Endopeptidasas/genética , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Silenciador del Gen , Isoflurano/efectos adversos , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Apoptosis , Análisis de los Gases de la Sangre , Disfunción Cognitiva/psicología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto , Complicaciones Posoperatorias , ARN Mensajero , Ratas , Transducción de Señal , Memoria EspacialRESUMEN
BACKGROUND: Major resection (MR) is recommended for cases with T2 finding after local excision (LE) of early rectal cancer, but the revision procedure is accompanied with high morbidity. We evaluated the oncological safety of LE followed by adjuvant radiotherapy as a rectum-preserving alternative to MR for T2 early rectal cancer. METHODS: A total of 3786 patients with T2N0M0 rectal adenocarcinoma between 1998 and 2013 were included from the SEER database. Survival rates were compared using the Kaplan-Meier method with a log-rank test, and multivariate analyses were performed using Cox proportional regression models. RESULTS: Of these patients included, 429 (11.3%) treated with LE alone (LE group), 3067 (81.0%) treated with MR (MR group), and 290 (7.7%) treated with LE followed by adjuvant radiotherapy (LE + adjuvant RT group). The 5-year cancer specific survival (CSS) rate and 5-year overall survival (OS) rate were significantly lower in LE patients group than those in MR patients group (70.5% vs. 81.8%, P < 0.001; 57.3% vs. 72.3%, P < 0.001). The 5-year CSS rate and 5-year OS rate were similar between LE + adjuvant RT and MR groups (78.4% vs. 81.8%, P = 0.975, and 70.7% vs. 72.3%, P = 0.311, respectively). Multivariate Cox regression revealed that treatment strategies, age and CEA status were independently associated with CSS and OS. After age adjustment, LE was associated with reduced CSS (using MR as a reference, HR, 1.784; P < 0.001) and reduced OS (HR, 1.739; P < 0.001). However, CSS and OS related to LE + adjuvant RT of T2 rectal cancer group weren't be affected (HR, 0.994; P = 0.962 and HR, 0.904; P = 0.302, respectively). CONCLUSIONS: When MR is inappropriate for T2 early rectal cancer patients because of patients refusal or co-morbidities, LE + adjuvant RT can provide acceptable levels of long-term survival.
Asunto(s)
Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Tasa de Supervivencia , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia Adyuvante , Neoplasias del Recto/epidemiología , Neoplasias del Recto/patología , Sistema de Registros , Programa de VERF , Estados Unidos/epidemiologíaRESUMEN
The present study aimed to investigate the influence of UGT1A9 gene polymorphisms on the efficacy of propofol in patients undergoing the painless induced abortion method. A total of 156 women seeking voluntary pregnancy termination procedures were selected for the study, and subsequently underwent painless induced abortions, following anesthesia by means of propofol administration. PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to detect the polymorphisms of UGT1A9 gene at -440C/T, -1818C/T, and -1887T/G loci. The time, effect-site concentration, and bispectral index (BIS) for the Observer's Assessment of Alertness/Sedation (OAA/S) (up to 4 points) were observed and recorded in patients following discontinuation of propofol. The time and effect-site concentration for BIS reaching 80 in patients following the discontinuation of propofol were observed and recorded. Postoperative observations of adverse reactions, such as nausea, vomiting, and respiratory depression were all made record of. In comparison with patients with UGT1A9 -440C/T CT and TT, those with UGT1A9 -440C/T CC displayed shorter durations of OAA/S by up to 4 points, shorter BIS times reaching 80, as well as higher corresponding effect-site concentrations. No significant differences were detected in the patients with -440C/T, -1818T/C, and -1887T/G in incidence of nausea, vomiting, and respiratory depression. The findings of the study highlighted correlation between UGT1A9 -440C/T gene polymorphisms and positive propofol efficacy in patients undergoing painless induced pregnancy termination procedures.
Asunto(s)
Aborto Inducido/efectos adversos , Glucuronosiltransferasa/genética , Dolor/genética , Propofol/uso terapéutico , Adulto , Anestesia/efectos adversos , Femenino , Humanos , Dolor/tratamiento farmacológico , Dolor/patología , Manejo del Dolor/efectos adversos , Polimorfismo de Nucleótido Simple , Embarazo , Propofol/efectos adversos , UDP Glucuronosiltransferasa 1A9RESUMEN
Aims. To compare the surgical and oncological outcomes of rectal mucinous adenocarcinomas treated with neoadjuvant chemoradiotherapy versus surgery alone. Methods. A total of 167 locally advanced rectal mucinous adenocarcinoma patients treated with neoadjuvant chemoradiotherapy and surgery alone between 2008 and 2014 were matched using propensity score; the surgical and oncological outcomes were compared. Results. Ninety-six patients were matched. Postoperative morbidity was similar between groups. Sphincter preservation rate was higher in patients receiving neoadjuvant chemoradiotherapy (79.2% versus 60.4%, P = 0.045), especially for tumors ≥ 3 cm but ≤5 cm from the anal verge (75.0% versus 44.0%, P = 0.036). With a median follow-up of 54.8 months, the 5-year overall survival rate (neoadjuvant chemoradiotherapy versus surgery alone: 79.6% versus 67.1%; P = 0.599) and disease-free survival rate (75.6% versus 64.2%; P = 0.888) were similar. The 5-year local recurrence rate was lower in patients receiving neoadjuvant chemoradiotherapy (7.7% versus 26.0%, P = 0.036), while no difference was observed in distant metastasis. A poor response to chemoradiation was associated with higher local recurrence (P = 0.037). Conclusions. Compared with surgery alone, neoadjuvant chemoradiotherapy was found to increase the sphincter preservation rate and reduce local recurrence, thus being beneficial for locally advanced rectal mucinous adenocarcinoma patients.
RESUMEN
Activation of the triggering receptor expressed on myeloid cells 2 (TREM-2) regulates myeloid cell function in vitro. However, the failure to detect TREM-2 protein expression in vivo has hampered studies on immunological and other physiological TREM-2 functions. This study demonstrates that TREM-2 is expressed by human mesenchymal stem cells (h-MSCs) and responds to the toll-like receptor (TLR) ligand lipopolysaccharide (LPS). Knockdown of TREM-2 in h-MSCs using a small interfering RNA (siRNA) reduced the expression levels of TLR2, TLR4, and TLR6, inhibited osteogenic, chondrogenic, and adipogenic differentiation under specific induction conditions, and enhanced LPS-evoked inflammatory cytokine production. Thus, activation of TREM-2 may restrain h-MSC immune activation and promote differentiation for tissue repair.