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1.

Background

Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function.

Objective

This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced killer cells (DC/CIKs) against pancreatic cancer (PC).

Methods

PC-derived exosomes (PEs) were extracted from cultured PANC-1 cell supernatants and then ruptured; this was followed by ultrafiltered exosome lysates (UELs). DCs were stimulated with lipopolysaccharide (LPS), PE, and UEL, followed by co-culture with CIKs. The anti-tumor effects of DC/CIKs against PC were evaluated by proliferation and killing rates, tumor necrosis factor-α (TNF-α) and perforin secretion. Exosomal miRNAs were depleted after lysis and ultrafiltration, while 128 proteins were retained, including several immune-activating proteins.

Results

UEL-stimulated DC/CIKs showed a higher killing rate than LPS- and PE-stimulated DC/CIKs.

Conclusions

miRNA-depleted exosome proteins may be promising agonists for specifically activating DC/CIKs against PC.
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2.

Objectives

The aim of the study is to evaluate the cognitive-enhancing effects of hydrolysate of polygalasaponin (HPS) on senescence accelerate mouse P8 (SAMP8) mice, an effective Alzheimer’s disease (AD) model, and to research the relevant mechanisms.

Methods

The cognitive-enhancing effects of HPS on SAMP8 mice were assessed using Morris water maze (MWM) and step-through passive avoidance tests. Then N-methyl-d-aspartate (NMDA) receptor subunit expression for both the cortex and hippocampus of mice was observed using Western blotting.

Results

HPS (25 and 50 mg/kg) improved the escape rate and decreased the escape latency and time spent in the target quadrant for the SAMP8 mice in the MWM after oral administration of HPS for 10 d. Moreover, it decreased error times in the passive avoidance tests. Western blotting showed that HPS was able to reverse the levels of NMDAR1 and NMDAR2B expression in the cortex or hippocampus of model mice.

Conclusions

The present study suggested that HPS can improve cognitive deficits in SAMP8 mice, and this mechanism might be associated with NMDA receptor (NMDAR)-related pathways.
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3.

Objective

The purpose of this study was to determine the role of Ureaplasma urealyticum-derived lipidassociated membrane proteins (LAMPs) in the host innate immune system, specifically their effect on Toll-like receptors (TLRs).

Methods

LAMPs were derived from U. urealyticum strains, and human amniotic epithelial cells (HAECs) were isolated from healthy full-term placentas. Cytokine concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and TLR2 mRNA by real-time PCR. Expression of TLR2 was confirmed by Western blotting and immunohistochemistry.

Results

LAMPs induced HAECs to produce inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α. Cytokine production was reduced after blocking TLR2 using TLR2 inhibitor (anti-hTLR2-IgA).

Conclusions

LAMPs isolated from U. urealyticum induced TLR2-dependent up-regulation of inflammatory genes and cytokines in HAECs.
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4.

Objective

The aim of this study was to evaluate the safety and efficiency of enucleation (EU) for proximal pancreatic non-invasive neoplasms.

Methods

Patients with solitary non-invasive neoplasms in the proximal pancreas from January 1998 to April 2014 at the Second Affiliated Hospital of Zhejiang University, Hangzhou, China were included. Different operations and outcomes were analyzed.

Results

A total of 123 patients were enrolled. Forty patients (32.5%) underwent EU including 18 patients who had tumors close to the main pancreatic duct (MPD). Sixty-one patients (49.6%) had pancreaticoduodenectomy (PD) performed and 22 (17.9%) underwent central pancreatectomy (CP). Pathological outcomes included neuroendocrine tumors, cystic lesions, and solid pseudopapillary tumors. Operation time, intra-operative blood loss, and duration of hospital stay were significantly reduced in the EU group. PD was associated with the greatest complication rate (55.7%), followed by EU (50%) and CP (40.9%), though the pancreatic fistula rate after EU was the highest (50%), especially in patients with tumors larger than 3 cm and tumors close to the MPD. EU had advantages in the preservation of pancreatic parenchyma and endocrine and exocrine function.

Conclusions

EU can be carried out safely and effectively for tumors in the proximal pancreas with improved outcomes compared with standard resections, even if the tumor is larger than 3 cm and close to the MPD.
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5.

Objective

Three mainstream techniques—laparoscopic hepatectomy (LH), percutaneous radiofrequency ablation (pRFA), and open hepatectomy (OH)—were compared in this study, in terms of their efficacies in the treatment of small hepatocellular carcinoma (HCC).

Methods

A comparative study was performed within a total of 94 patients diagnosed with small HCC in our hospital from 2005 to 2010, who underwent LH (28), RFA (33), or OH (33). They had either a single tumor lesion of less than 5 cm or up to three nodules with diameters of less than 3 cm each. Outcomes were carefully evaluated throughout a 3-year follow-up interval and statistically interpreted.

Results

The pRFA group had a significantly lower disease-free survival rate compared with the two surgical groups (P=0.001) and significantly shorter overall survival (P=0.005), while the LH group and the OH group had no difference in survival results. For patients younger than 60 years old, surgical approaches offered a better long-term overall survival prognosis (P=0.008). There were no statistically significant differences among the three groups in overall survival for elderly patients (P=0.104).

Conclusions

Among patients with small HCC, LH may provide better curative effects than pRFA without increasing complication rates. pRFA leads to faster recurrence than surgical resections. LH has similar therapeutic effects to OH and causes less trauma. For patients younger than 60 years old, LH may be the best curative treatment. Elderly patients may choose either surgery or pRFA.
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6.
7.

Objective

The aim of this study was to explore the association of dopamine receptor D2 (DRD2) polymorphism and alleviation of obesity in children and adolescents after 8-year follow-up.

Methods

This retrospective cohort study included obese children and adolescents with a follow-up period of 8 years. Baseline clinical characteristics and DRD2 polymorphisms (including rs1076562, rs2075654, and rs4586205) were extracted from medical records. A follow-up visit was performed in May 2017 to collect related data including height, weight, diet compliance, and exercise compliance.

Results

One hundred and nine obese children and adolescents were included in the current study. Among three DRD2 single nucleotide polymorphisms, only rs2075654 had a statistically significant association with alleviation of obesity, as the alleviation rate for minor allele carriers (68.6% for TC+TT) was higher compared to the major allele homozygote (43.3% for CC). After adjusting for all related factors, the hazard ratio of rs2075654 minor allele carriers for the alleviation of obesity was 3.34 (95% confidence interval (CI): 1.30?8.58).

Conclusions

The rs2075654 polymorphism of DRD2 is related to long-term obesity alleviation in obese Chinese children and adolescents.
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8.

Objective

The aim of the current study was to evaluate the effect of ultraviolet (UV) photofunctionalization of dental titanium implants with exposure to the oral cavity on osseointegration in an animal model.

Methods

Forty-eight titanium implants (Camlog® Conelog® 4.3 mmx9.0 mm) were placed epicrestally into the edentulous jaws of three minipigs and implant stability was assessed by measuring the implant stability quotient (ISQ). Prior to implantation half of the implants were photofunctionalized with intense UV-light. After three months, the implants were exposed and ISQ was measured again. After six months of implant exposure, the minipigs were sacrificed and the harvested specimens were analyzed using histomorphometric, light, and fluorescence microscopy.

Main results

Forty-two of 48 implants osseointegrated. The overall mean bone-implant contact area (BIC) was (64±22)%. No significant differences were found in BIC or ISQ value (multivariate analysis of variance (MANOVA), P>0.05) between implants with and without exposure to UV photofunctionalization.

Conclusions

No significant effects were observed on osseointegration of dental titanium implants nine months after exposure of UV photofunctionalization.
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9.
10.

Objectives

We retrospectively reviewed the urethral stricture cases treated in our tertiary center, and assessed the safety and feasibility of the high-pressure balloon dilation (HPBD) technique for anterior urethral stricture.

Methods

From January 2009 to December 2012, a total of 31 patients with anterior urethral strictures underwent HPBD at our center, while another 25 cases were treated by direct vision internal urethrotomy (DVIU). Patient demographics, stricture characteristics, surgical techniques, and operative outcomes were assessed and compared between the two groups. The Kaplan-Meier survival analysis was applied to evaluate the stricture-free rate for the two surgical techniques.

Results

The operation time was much shorter for the HPBD procedure than for the DVIU ((13.19±2.68) min vs. (18.44±3.29) min, P<0.01). For the HPBD group, the major postoperative complications as urethral bleeding and urinary tract infection (UTI) were less frequently encountered than those in DVIU (urethral bleeding: 2/31 vs. 8/25, P=0.017; UTI: 1/31 vs. 6/25 P=0.037). The Kaplan-Meier survival analysis showed that there was no significant difference in stricture-free rate at 36 months between the two groups (P=0.21, hazard ratio (HR)=0.65, 95% confidence interval (CI): 0.34 to 1.26). However, there was a significantly higher stricture-free survival in the HPBD group at 12 months (P=0.02, HR=0.35, 95% CI: 0.14 to 0.87), which indicated that the stricture recurrence could be delayed by using the HPBD technique.

Conclusions

HPBD was effective and safe and it could be considered as an alternative treatment modality for anterior urethral stricture disease.
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11.

Objective

Keloids are exuberant cutaneous scars that form due to abnormal growth of fibrous tissue following an injury. The primary aim of this study was to assess the efficacy and mechanism of hyperbaric oxygen therapy (HBOT) to reduce the keloid recurrence rate after surgical excision and radiotherapy.

Methods

(1) A total of 240 patients were randomly divided into two groups. Patients in the HBOT group (O group) received HBOT after surgical excision and radiotherapy. Patients in the other group were treated with only surgical excision and radiotherapy (K group). (2) Scar tissue from recurrent patients was collected after a second operation. Hematoxylin and eosin (H&E) staining was used to observe keloid morphology. Certain inflammatory factors (interleukin-6 (IL-6), hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α), nuclear factor κB (NF-κB), and vascular endothelial growth factor (VEGF)) were measured using immunohistochemical staining.

Results

(1) The recurrence rate of the O group (5.97%) was significantly lower than that of the K group (14.15%), P<0.05. Moreover, patients in the O group reported greater satisfaction than those in the K group (P<0.05). (2) Compared with the recurrent scar tissue of the K group, the expression levels of the inflammatory factors were lower in the recurrent scar tissue of the O group.

Conclusions

Adjunctive HBOT effectively reduces the keloid recurrence rate after surgical excision and radiotherapy by improving the oxygen level of the tissue and alleviating the inflammatory process.
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12.

Purpose

Metalloproteinases are a key component of the pathogenesis of abdominal hernias. Obesity is considered a risk factor in herniogenesis and hernia recurrence. The aim of this study was to evaluate the serum concentrations of metalloproteinase-2 (MMP-2), MMP-9, MMP-13, and adiponectin in morbidly obese and nonoverweight controls.

Materials and methods

The participants were recruited from among patients undergoing bariatric and non-bariatric surgery and divided into two groups: I (body mass index (BMI)≥35 kg/m2, n=40) and II (BMI<25 kg/m2, n=30). Serum concentrations of MMP-2, MMP-9, MMP-13, and adiponectin were measured using enzyme-linked immunosorbent assay (ELISA).

Results

A statistically significant difference between groups was observed for MMP-2 concentration. The median MMP-9 concentration was higher in the obese group, but the difference was not statistically significant. Median MMP-13 concentrations did not differ between groups. Serum adiponectin concentration was insignificantly higher in the non-obese group.

Conclusions

The elevated serum MMP-2 and MMP-9 concentrations in obese individuals may be related to the higher incidence of incisional hernias in this population.
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13.

Objective

The aim of this study was to compare complications and oncologic outcomes of patients undergoing laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (LDP) at a single center.

Methods

Distal pancreatectomies performed for pancreatic ductal adenocarcinoma during a 4-year period were included in this study. A retrospective analysis of a database of this cohort was conducted.

Results

Twenty-two patients underwent LDP for pancreatic ductal adenocarcinoma, in comparison to seventy-six patients with comparable tumor characteristics treated by LDP. No patients with locally advanced lesions were included in this study. Comparing LDP group to LDP group, there were no significant differences in operation time (P=0.06) or blood loss (P=0.24). Complications (pancreatic fistula, P=0.62; intra-abdominal abscess, P=0.44; postpancreatectomy hemorrhage, P=0.34) were similar. There were no significant differences in the number of lymph nodes harvested (11.2±4.6 in LDP group vs. 14.4±5.5 in LDP group, P=0.44) nor the rate of patients with positive lymph nodes (36% in LDP group vs. 41% in LDP group, P=0.71). Incidence of positive margins was similar (9% in LDP group vs. 13% in LDP group, P=0.61). The mean overall survival time was (29.6±3.7) months for the LDP group and (27.6±2.1) months for LDP group. There was no difference in overall survival between the two groups (P=0.34).

Conclusions

LDP is a safe and effective treatment for selected patients with pancreatic ductal adenocarcinoma. A slow-compression of pancreas tissue with the GIA stapler is effective in preventing postoperative pancreatic fistula. The oncologic outcome is comparable with the conventional open approach. Laparoscopic radical antegrade modular pancreatosplenectomy contributed to oncological clearance.
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14.

Objective

Hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of microRNA-718 (miR-718) in the malignant phenotype of HCC cells and its possible role in HCC diagnosis.

Methods

Here we first used a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein (GFP) reporter assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype.

Results

We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 (EGR3) is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the viability and proliferation of HCC cells, and promot the migration and invasion of HCC cells.

Conclusions

miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic marker and treatment target for HCC.
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15.

Objective

The present study aims at determining the stability of a popular type 2 diabetes rat model induced by a high-fat diet combined with a low-dose streptozotocin injection.

Methods

Wistar rats were fed with a high-fat diet for 8 weeks followed by a one-time injection of 25 or 35 mg/kg streptozotocin to induce type 2 diabetes. Then the diabetic rats were fed with regular diet/high-fat diet for 4 weeks. Changes in biochemical parameters were monitored during the 4 weeks.

Results

All the rats developed more severe dyslipidemia and hepatic dysfunction after streptozotocin injection. The features of 35 mg/kg streptozotocin rats more resembled type 1 diabetes with decreased body weight and blood insulin. Rats with 25 mg/kg streptozotocin followed by normal diet feeding showed normalized blood glucose level and pancreatic structure, indicating that normal diet might help recovery from certain symptoms of type 2 diabetes. In comparison, diabetic rats fed with high-fat diet presented decreased but relatively stable blood glucose level, and this was significantly higher than that of the control group (P&gt;0.05).

Conclusions

This model easily recovers with normal diet feeding. A high-fat diet is suggested as the background diet in future pharmacological studies using this model.
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16.

Objective

In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis.

Methods

The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs).

Results

We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis.

Conclusions

Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate.
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17.
18.

Objectives

The study was done to evaluate the efficacy of optical coherence tomography (OCT), to detect and analyze the microdamage occurring around the microimplant immediately following its placement, and to compare the findings with micro-computed tomography (μCT) images of the samples to validate the result of the present study.

Methods

Microimplants were inserted into bovine bone samples. Images of the samples were obtained using OCT and μCT. Visual comparisons of the images were made to evaluate whether anatomical details and microdamage induced by microimplant insertion were accurately revealed by OCT.

Results

The surface of the cortical bone with its anatomical variations is visualized on the OCT images. Microdamage occurring on the surface of the cortical bone around the microimplant can be appreciated in OCT images. The resulting OCT images were compared with the μCT images. A high correlation regarding the visualization of individual microcracks was observed. The depth penetration of OCT is limited when compared to μCT.

Conclusions

OCT in the present study was able to generate high-resolution images of the microdamage occurring around the microimplant. Image quality at the surface of the cortical bone is above par when compared with μCT imaging, because of the inherent high contrast and high-resolution quality of OCT systems. Improvements in the imaging depth and development of intraoral sensors are vital for developing a real-time imaging system and integrating the system into orthodontic practice.
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19.

Objective

To report surgical management and favorable outcome in a case with delayed repair of traumatic laser in situ keratomileusis (LASIK) flap dislocation with shrinkage and folds.

Methods

A 30-year-old man with a five-year history of bilateral LASIK experienced blunt trauma to his right eye followed by decreased vision for 5 weeks. The surgical management included initially softening the flap by irrigation with balanced salt solution (BSS). The shrinkage folds were carefully and gently stretched by scraping with a 26-gauge cannula accompanied by BSS irrigation. All of the epithelial ingrowth on the flap inner surface and on the bed was thoroughly debrided by scraping and irrigation. After the flap was repositioned to match its original margin, a soft bandage contact lens was placed.

Results

At his initial visit, slit-lamp microscopy and optical coherence tomography (OCT) showed shrinkage of the LASIK flap with an elevated margin approximately 3 mm above the original position. The flap covered half of the pupil and had multiple horizontal folds. Two months after surgery, the flap remained well positioned with only faint streaks in the anterior stroma. The uncorrected visual acuity of the right eye was 20/20 with a manifest refraction of Plano.

Conclusions

For delayed repair of traumatically dislocated LASIK flaps, sufficient softening by BSS, stretching the shrinkage folds, and thorough debridement of ingrowth epithelium enable resetting the flap and provide satisfactory results.
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20.

Objective

To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection (HR) for breast cancer liver metastases (BCLMs).

Methods

Studies that had examined the outcomes for both RFA and HR for BCLM were identified by searching the electronic databases PubMed, EMBASE, and the Cochrane Library. Pooled analyzes of the overall survival (OS), disease-free survival (DFS), and short-term outcomes of BCLM were performed.

Results

Patients with BCLM gained many more survival benefits from HR than from RFA with regard to the 3-year OS rate (combined odds ratio (OR) 0.41, 95% confidence interval (CI) 0.29–0.59, P<0.001), 5-year OS rate (combined OR 0.38, 95% CI 0.32–0.46, P<0.001), 3-year DFS (combined OR 0.36, 95% CI 0.27–0.49, P<0.001), and 5-year DFS (combined OR 0.51, 95% CI 0.40–0.66, P<0.001). RFA had fewer postoperative complications (combined OR 0.30, 95% CI 0.20–0.44, P<0.001) and shorter hospital stays (combined OR -9.01, 95% CI -13.49–4.54, P<0.001) than HR.

Conclusions

HR takes precedence over RFA in the treatment of patients with BCLM, considering the better survival rate. RFA gives rise to fewer complications and can be carried out with a shorter hospital stay, compared to HR. RFA should be reserved for patients who are not optimum candidates for resection.
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