Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress.

Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress play a pivotal role in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). In this study, we found that blueberry-derived exosomes-like nanoparticles (BELNs) could ameliorate oxidative stress in rotenone-induced HepG2 cells and high-fat diet (HFD)-fed C57BL/6 mice. Preincubation with BELNs decreased the level of reactive oxygen species (ROS), increased the mitochondrial membrane potential, and prevented cell apoptosis by inducing the expression of Bcl-2 and heme oxygenase-1 (HO-1) and decreasing the content of Bax in rotenone-treated HepG2 cells. We also found that preincubation with BELNs accelerated the translocation of Nrf2, an important transcription factor of antioxidative proteins, from the cytoplasm to the nucleus in rotenone-treated HepG2 cells. Moreover, administration of BELNs improved insulin resistance, ameliorated the dysfunction of hepatocytes, and regulated the expression of detoxifying/antioxidant genes by affecting the distribution of Nrf2 in the cytoplasm and nucleus of hepatocytes of HFD-fed mice. Furthermore, BELNs supplementation prevented the formation of vacuoles and attenuated the accumulation of lipid droplets by inhibiting the expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1), the two key transcription factors for de novo lipogenesis in the liver of HFD-fed mice. These findings suggested that BELNs can be used for the treatment of NAFLD because of their antioxidative activity.

Alteration of gut microbiota and metabolomics in critically ill patients by sequential feeding: A pilot study.

BACKGROUND: Sequential feeding (SF) is a new feeding mode for critically ill patients that involves a combination of continuous feeding (CF) in the beginning, rhythmic feeding in the second stage, and oral feeding in the last stage. In this study, we investigated the influence of SF on gut microbiota and metabolomics in critically ill patients. METHODS: Stool specimens from 20 patients (10 patients with the SF group, 10 patients with the CF group) were collected for full-length 16S ribosomal RNA gene sequencing and untargeted metabolomics analysis. RESULTS: The proportion of patients with low bacterial diversity (Shannon index < 4) in the SF group was much lower than that in the CF group, but there was no significant difference in the proportions (20% vs 50%, P = .350). The abundances of Actinobacteria/Actinobacteria (at the phylum and class levels), Pseudomonadaceae/Pseudomonas (at the family and genus levels), and Fusobacteria/Fusobacteriaceae/Fusobacteriales/Fusobacteria/Fusobacterium (at the phylum, class, order, family, and genus levels) were all higher in the SF group than in the CF group. Actinobacteria/Actinobacteria (at the phylum and class levels) were the most influential of these gut flora. Retinoic acid and leucine were upregulated in the SF group and were respectively responsible for the intestinal immune network for immunoglobulin A production and the mammalian target of rapamycin signaling pathway in the enriched pathways according to the Kyoto Encyclopedia of Genes and Genomes database classification. CONCLUSIONS: SF could alter gut microbiota and metabolomics in critically ill patients. Because of the small sample size, further study is required.

Prevalence, Risk Factors And Location Of Skip Metastasis In Papillary Thyroid Carcinoma: A Systematic Review And Meta-Analysis.

BACKGROUND: Skip metastasis is a special type in cervical lymph node metastasis (LNM) of patients diagnosed with papillary thyroid carcinoma (PTC) which induced poor prognosis. There are few studies about skip metastasis and conclusions remained uncertain. Therefore, this study aims to explore the frequency and to investigate risk factors of skip metastasis in PTC. METHODS: Through searching the keyword by PubMed and Embase databases which articles published up to 1st August 2018 about skip metastasis in papillary thyroid carcinoma, we extract data in order to assure whether those materials meet the criteria. RESULTS: The prevalence of skip metastasis is 12.02% in light of our meta-analysis of 18 studies with 2165 patients. The upper pole location (RR = 3.35, 95% CI =1.65-6.79, P = 0.0008) and tumors size ≤1 cm (RR = 2.65, 95% CI =1.50-4.70, P = 0.0008) are significantly associated with skip metastasis, whereas lymphovascular invasion (RR = 0.33, 95% CI =0.15-0.75, P = 0.0083) exists lower rate of skip metastasis. Multifocality, gender, age, bilaterality, thyroiditis and Extrathyroidal extension (ETE) are insignificantly associated with skip metastasis. Level II and level III are the most frequently affected areas. CONCLUSION: The lateral compartment should be carefully examined especially for those PTC patients who present primary tumors in the upper lobe with a primary tumor size ≤10 mm which could be detected with skip metastasis.

Effectiveness evaluation of computer-aided diagnosis system for the diagnosis of thyroid nodules on ultrasound: A systematic review and meta-analysis.

BACKGROUND: More and more automated efficient ultrasound image analysis techniques, such as ultrasound-based computer-aided diagnosis system (CAD), were developed to obtain accurate, reproducible, and more objective diagnosis results for thyroid nodules. So far, whether the diagnostic performance of existing CAD systems can reach the diagnostic level of experienced radiologists is still controversial. The aim of the meta-analysis was to evaluate the accuracy of CAD for thyroid nodules' diagnosis by reviewing current literatures and summarizing the research status. METHODS: A detailed literature search on PubMed, Embase, and Cochrane Libraries for articles published until December 2018 was carried out. The diagnostic performances of CAD systems vs radiologist were evaluated by meta-analysis. We determined the sensitivity and the specificity across studies, calculated positive and negative likelihood ratios and constructed summary receiver-operating characteristic (SROC) curves. Meta-analysis of studies was performed using a mixed-effect, hierarchical logistic regression model. RESULTS: Five studies with 536 patients and 723 thyroid nodules were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) for CAD system were 0.87 (95% confidence interval [CI], 0.73-0.94), 0.79 (95% CI 0.63-0.89), 4.1 (95% CI 2.5-6.9), 0.17 (95% CI 0.09-0.32), and 25 (95% CI 15-42), respectively. The SROC curve indicated that the area under the curve was 0.90 (95% CI 0.87-0.92). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and DOR for experienced radiologists were 0.82 (95% CI 0.69-0.91), 0.83 (95% CI 0.76-0.89), 4.9 (95% CI 3.4-7.0), 0.22 (95% CI 0.12-0.38), and 23 (95% CI 11-46), respectively. The SROC curve indicated that the area under the curve was 0.96 (95% CI 0.94-0.97). CONCLUSION: The sensitivity of the CAD system in the diagnosis of thyroid nodules was similar to that of experienced radiologists. However, the CAD system had lower specificity and DOR than experienced radiologists. The CAD system may play the potential role as a decision-making assistant alongside radiologists in the thyroid nodules' diagnosis. Future technical improvements would be helpful to increase the accuracy as well as diagnostic efficiency.

The function of carbon nanoparticles to improve lymph node dissection and identification of parathyroid glands during thyroid reoperation for carcinoma.

To evaluate the function of carbon nanoparticles during the thyroid reoperation for carcinoma, we conducted this study by retrospectively analyzing the data of patients who underwent at least completion thyroidectomy with bilateral central lymph nodes dissection for thyroid carcinoma from January 2009 to June 2016. The clinicopathologic characteristics and surgical details were compared between the patient who accepted intraoperative carbon nanoparticles injection and those who accepted nothing injection during the surgery. The main monitoring indicators were the number of dissected lymph nodes and metastatic lymph nodes in central zone, the number of identified parathyroid glands and autoplastic parathyroid glands and unintentionally resected parathyroid glands. A total of 69 patients were enrolled into the carbon nanoparticles group and 128 patients were enrolled into the control group.The average number of lymph nodes harvested in the central zone was higher in the carbon nanoparticles group than that in the control group (11.2 ±â€Š5.7 vs 7.7 ±â€Š4.0, P < .001), so was the average number of metastatic lymph nodes (4.5 ±â€Š4.5 vs 2.7 ±â€Š2.9, P = .004). The average number of identified parathyroid gland was greater in the carbon nanoparticles group than that in the control group (2.4 ±â€Š1.2 vs 1.6 ±â€Š1.1, P < .001). The average number of autoplastic parathyroid gland was comparable between the 2 groups (0.6 ±â€Š0.6 vs 0.4 ±â€Š0.7, P = .052). But the average number of unintentionally resected parathyroid gland was less in the carbon nanoparticles group than that in the control group (0.1 ±â€Š0.2 vs 0.2 ±â€Š0.4, P = .007). Carbon nanoparticles can improve lymph nodes dissection and identification of parathyroid gland during thyroid reoperation for carcinoma.

MicroRNA-876-3p functions as a tumor suppressor gene and correlates with cell metastasis in pancreatic adenocarcinoma via targeting JAG2.

Dysregulation of microRNA (miRNA) expression in multiple cancers and their vital roles in malignant cancer progression are well investigated. The purpose of this study was to explore the biological roles of miR-876-3p in pancreatic cancer. We used genome-wide gene expression analysis in clinical pancreatic adenocarcinoma samples to identify miR-876-3p down-regulated in pancreatic cancer. We then collected 22 pairs of pancreatic cancer and the corresponding non-cancerous tissues to determine miR-876-3p level, and confirmed that miR-876-3p was significantly down-regulated in pancreatic cancer. Furthermore, functional analysis suggested that overexpression of miR-876-3p suppressed cell growth and aggressively increased cells apoptosis in BXPC-3 and PANC-1 cells, whereas down-regulation led to the opposite results. We identified Jagged2 (JAG2) as a direct target of miR-876-3p, and an inverse correlation between miR-876-3p and JAG2 was observed in pancreatic adenocarcinoma. Moreover, miR-876-3p and a JAG2 siRNA were co-transfected into both PANC-1 and BXPC-3 cells to explore the mechanism of miR-876-3p and JAG2 on pancreatic adenocarcinoma tumorigenesis. Down-regulation of JAG2 inhibited the overexpression effects of miR-876-3p, and up-regulation of JAG2 reversed the effects of overexpressed miR-876-3p. Cumulatively, these results revealed a significant role of the miR-876-3p/JAG2 axis in suppressing pancreatic adenocarcinoma cell growth and aggressiveness.

Second generation of familial nonmedullary thyroid carcinoma: A meta-analysis on the clinicopathologic features and prognosis.

Whether the second generation of parent/offspring type familial nonmedullary thyroid carcinoma (FNMTC) is more aggressive and has worse prognosis than their first generation counterpart is controversial. To evaluate the clinicopathologic features and prognosis of the second generation via a comparison between the two groups, We searched three databases (PubMed, EMBASE and the Cochrane library) to review studies published before November 25, 2016. All original studies comparing the clinicopathologic features and prognosis in the first generation of parent/offspring type FNMTC with its second generation counterpart were included. The Q-test and I2 test were used to evaluate homogeneity and funnel plot with Egger's test was used to evaluate publication bias. 6 studies, including 424 subjects were included. There was significant difference between the first and second generation of parent/offspring type FNMTC in the age of onset (SMD = -1.20, 95% CI: -2.38, -0.03, p = 0.045), gender distribution (OR = 0.48, 95% CI: 0.25, 0.90, p = 0.022) and lymph node metastasis (OR = 1.84, 95%CI: 1.16, 2.92, p = 0.01), while no significant difference in other variables. Thus we conclude that the second generation of parent/offspring type FNMTC patients is in higher risk than their first generation counterpart. We believe continuous study is needed to confirm the result.

Evaluating the effectiveness of prophylactic central neck dissection with total thyroidectomy for cN0 papillary thyroid carcinoma: An updated meta-analysis.

BACKGROUND: The effectiveness of prophylactic central neck dissection (pCND) following total thyroidectomy (TT) in patients with clinical node-negative (cN0) papillary thyroid carcinoma (PTC) is still controversial. The aim of this meta-analysis is to evaluate the outcome of pCND and to provide quantitative evidence. METHOD: A detailed literature search of PubMed, EMBASE, ClinicalTrails.gov and Cochrane Library electronic databases for articles published up to October 2016 was carried out. This meta-analysis was performed by the random method (Mantel-Haenszel) model. Locoregional recurrence (LRR) and surgical complications were analyzed. RESULTS: Twenty-two studies comparing pCND + TT (combined) and TT alone in cN0 PTC patients were analyzed. A total of 6930 cases were enrolled, including 2381 cases in the combined group and 4009 cases in the TT-alone group. Compared with TT alone, patients in the combined group showed a significantly lower rate of overall LRR (OR = 0.66, 95% CI = 0.48-0.89) and central compartment recurrence (OR = 0.40, 95% CI = 0.22-0.73). There was no statistical difference in the rate of lateral compartment recurrence. However, the combined group showed a significantly higher rate of temporary and permanent hypoparathyroidism (OR = 2.28, 95% CI = 1.92-2.27/OR = 1.84, 95% CI = 1.15-2.95) and temporary recurrent laryngeal nerve injury (LNR) (OR = 1.53, 95% CI = 1.08-2.16). There was no statistical difference in the rate of permanent LNR, hematoma, hemorrhage or wound infection. CONCLUSIONS: This meta-analysis revealed that pCND with TT was a significantly efficient way to reduce the risk of LRR. However, pCND + TT increased the incidence rate of temporary and permanent hypoparathyroidism and temporary LNR.

Preoperative ultrasound-guided carbon nanoparticles localization for metastatic lymph nodes in papillary thyroid carcinoma during reoperation: A retrospective cohort study.

Due to the damaged anatomical structure and a large amount of fibrous and scar tissues in the surgical field, reoperation of papillary thyroid carcinoma is difficult. This study introduces a new method of locating metastatic lymph nodes during reoperation and evaluates the effectiveness and safety of the preoperative ultrasound-guided carbon nanoparticles (CNs) localization. This retrospective cohort study enrolled 52 patients who were diagnosed with lymph node metastasis by histopathology and underwent reoperation from October 2015 to February 2016. The modified radical neck dissection or selective neck node dissection was performed. A total of 26 patients underwent preoperative ultrasound-guided CNs injection, and other 26 patients did not. Tolerance, the result of injection, the number of resected metastatic lymph nodes, and postoperative complications were recorded and analyzed. In CNs group, 102 suspicious nonpalpable lesions in 26 patients were injected with CNs, and 99 of the 102 lesions were successfully identified by surgeon in the reoperation. The positive rate of resected lymph nodes in total, in the central compartment, and in the lateral compartment were 31.6%, 31.2%, and 32.8%, respectively, which was significantly higher than that in the control group (P < 0.001, P < 0.001, and P = 0.041). In addition, the positive rates of levels III, IV, and V in the CNs group were 35.6%, 21.9%, and 30.5%, respectively, which was significantly higher than that in the control group (P < 0.001, P = 0.005, and P = 0.01). In additional, in the CNs group, the rate of temporary hypoparathyroidism was significantly lower compared with the control group (0% vs 26.9%, P = 0.021). Preoperative ultrasound-guided CNs injection is a safe and effective method for localization of the metastatic lymph nodes during reoperation.

[Case-control study on endobutton plate or clavicular hook plate for the repair of acromioclavicular joint dislocations].

OBJECTIVE: To compare the treatment results between Endobutton plate and clavicular hook plate for the treatment of acromioclavicular joint dislocations. METHODS: From January 2009 to September 2010, 30 patients with acromioclavicular joint dislocations were treated with two different fixations: Endobutton plate (15 patients, including 12 males and 3 females, with a mean age of 38.5 +/- 8.2 years) and clavicular hook plate (15 patients, including 14 males and 1 female, with the mean age of 33.8 +/- 5.9 years). The mean operative time and blood loss were compared between the two groups. Joint function was assessed by the Karlsson standard. RESULTS: The mean operative time of the Endobutton group and the hook plate group were (61 +/- 8.6) min and (40 +/- 5.6) min. The average blood loss were (93 +/- 8.4) ml and (100 +/- 12.6) ml. There was no statistical difference between the two groups in the average blood loss and the mean operative time. According to the Karlsson standard, 13 patients got an excellent result, 2 good in the Endobutton group; and 7 patients got an excellent result and 7 good in hook plate group. The therapeutic effect in Endobutton group was better than that of hook plate group. CONCLUSION: In the treatment of acromioclavicular dislocation, fixation with Endobutton plate is believed to be better than hook plate fixation. It is an effective method for the repair of acromioclavicular joint dislocations in a short term. But its long term effects still need further follow up.