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Secondary amyloid A amyloidosis, a lethal complication, is induced when acute or chronic infection coexists with over-secretion of the serum amyloid A 1 (SAA1) protein and deposition in key internal organs. Previously, using the whole-exome sequencing method, we identified a novel deleterious mutation SAA1.2 in rheumatoid arthritis (RA) patients. However, the role of SAA1 in RA pathogenesis and its complications remains unknown. The purpose of this study was to determine the pathogenetic roles of SAA1 protein isoforms in RA progression. We modified an experimental adenovirus infection protocol to introduce SAA1.2 gene alleles into the knee joints of mice and used SAA1.3 and SAA1.5 as controls. Micro-computed tomography analysis was applied to determine changes in bone morphology and density. Immunohistochemical (IHC) analysis, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and real-time polymerase chain reaction (RT-PCR) were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction. We found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood resulted in the stimulation of immune responses, leading to CD8+ T cell and pro-inflammatory cytokine elevation, such as interleukin (IL)-6, IL-22, matrix metalloproteinase (MMP)-3, MMP-9, with subsequent synovial inflammation and bone destruction. These findings indicate that SAA1 protein isoforms, particularly SAA1.2, play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction of RA.

Long noncoding RNA SET-binding factor 2 (SBF2) antisense RNA 1 (AS1) is associated with the growth and metastasis of multiple cancer types, but its biological roles in serous ovarian carcinoma (SOC) remain unclear. In this study, the aberrant upregulation of SBF2-AS1 is detected in SOC after analysis of differentially expressed genes between SOC tissues and normal fallopian tubes from the public Gene Expression Omnibus (GEO) database. We determine that knockdown of SBF2-AS1 inhibits SOC cell proliferation and invasion by sponging miR-338-3p. MiR-338-3p acts as a tumor suppressor in SOC, and E26 transformation specific-1 (ETS1) is identified as a potential target of miR-338-3p regulation. Furthermore, SBF2-AS1 could modulate ETS1 by operating as a competing endogenous RNA for miR-338-3p. This finding elucidates a new mechanism for SBF2-AS1 in SOC development and provides a potential target for SOC therapeutic intervention.

Based on Hertzian theory and a theoretical model considering the flexibility of the carriage, this article established a model to describe how the vertical stiffness of preloaded linear rolling guides with cylinders changes.A method of iterative calculation is adopted to solve the problem.According to the results of finite element analysis, the deformation range of a double guide platform is predicted.

Background: SAA1 in RA pathogenesis and its complications remains unknown, making early diagnosis and risk prevention difficult. This study is to determine the pathogenetic mechanisms of three different SAA1 protein isoforms in RA progression. Methods: We modified an experimental adenovirus infection protocol in order to successfully introduce SAA1.2, SAA1.3, SAA1.5 gene alleles into the rear knee joints of C57BL/6 mice. Micro-computed tomography (micro-CT) analysis was applied to determine changes in bone morphology and density. Immunohistochemistry (IHC), flow cytometry, ELISA and real-time PCR were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction. Results: The pathogenetic functions of SAA1.2, SAA1.3 and SAA1.5 protein isoforms in promoting the initiation and progression of RA were determined. We established that SAA1.2 was the most aggressive factor in RA induction and progression. Mechanistically, we found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood results in stimulation of immune responses, leading to CD8+ T cell and pro-inflammatory cytokine elevation, with subsequent synovial inflammation and bone destruction. Conclusions: These findings indicate that SAA1 protein isoforms, particularly SAA1.2, play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction for RA.

Chemotherapy-induced nausea and vomiting (CINV) is the most common and severe side effects brought by chemotherapeutics. The role of music interventions in relieving CINV is uncertain. The aim of this systematic review was to test the effects of music interventions on three categories of CINV. A systematic search was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Biomedical Database (CBM) in order to capture randomized controlled trials (RCTs) investigating the comparative efficacy of music interventions and others. Two investigators screened, sorted, and extracted the data, and appraised the risk of bias. All statistical analyses were performed using RevMan 5.3 software. The literature search yielded 608 studies of which only ten RCTs fulfilled the eligibility criteria with 632 patients retrieved. Although the duration, the frequency of interventions, and the type of selected music varied across studies, commonly used elements included music listening. Results showed that music interventions were associated with reducing the incidence of anticipatory CINV and lowering the severity of delayed vomiting (MD = − 0.65, 95% CI = − 1.08 to − 0.23). However, strongly controversial results existed in terms of reducing the incidence of acute and delayed CINV, the severity of acute CINV, the severity of delayed nausea, and improving patients’ quality of life. Music interventions may effectively reduce the incidence of anticipatory CINV and relieve the severity of delayed vomiting in patients with chemotherapy based on limited data. However, the conclusion should be interpreted with caution and further research is required to design with large-scale and rigorous methods.

Background Currently, the identification of accurate biomarkers for the diagnosis of patients with early-stage lung cancer remains difficult. Fortunately, metabolomics technology can be used to improve the detection of plasma metabolic biomarkers for lung cancer. In a previous study, we successfully utilised machine learning methods to identify significant metabolic markers for early-stage lung cancer diagnosis. However, a related research platform for the investigation of tumour metabolism and drug efficacy is still lacking. Hypothesis/Purpose A novel methodology for the comprehensive evaluation of the internal tumour–metabolic profile and drug evaluation needs to be established. Methods The optimal location for tumour cell inoculation was identified in mouse chest for the non-traumatic orthotopic lung cancer mouse model. Microcomputed tomography (micro-CT) was applied to monitor lung tumour growth. Proscillaridin A (P.A) and cisplatin (CDDP) were utilised to verify the anti-lung cancer efficacy of the platform. The top five clinically valid biomarkers, including proline, L-kynurenine, spermidine, taurine and palmitoyl-L-carnitine, were selected as the evaluation indices to obtain a suitable lung cancer mouse model for clinical metabolomics research by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results The platform was successfully established, achieving 100% tumour development rate and 0% surgery mortality. P.A and CDDP had significant anti-lung cancer efficacy in the platform. Compared with the control group, four biomarkers in the orthotopic model and two biomarkers in the metastatic model had significantly higher abundance. Principal component analysis (PCA) showed a significant separation between the orthotopic/metastatic model and the control/subcutaneous/KRAS transgenic model. The platform was mainly involved in arginine and proline metabolism, tryptophan metabolism, and taurine and hypotaurine metabolism. Conclusion This study is the first to simulate clinical metabolomics by comparing the metabolic phenotype of plasma in different lung cancer mouse models. We found that the orthotopic model was the most suitable for tumour metabolism. Furthermore, the anti-tumour drug efficacy was verified in the platform. The platform can very well match the clinical reality, providing better lung cancer diagnosis and securing more precise evidence for drug evaluation in the future.

Background: Secondary amyloid A amyloidosis, a lethal complication, is induced when acute or chronic infection coexisted with over-secretion of the SAA1 protein and deposition of SAA1 in key internal organs. Previously, using the whole-exome sequencing method, we identified the novel deleterious mutation SAA1.2 in rheumatoid arthritis (RA) patients. However, the role of SAA1 in RA pathogenesis and its complications remains unknown, making early diagnosis and risk prevention difficult. Methods: We modified an experimental adenovirus infection protocol in order to successfully introduce SAA1.2, SAA1.3, SAA1.5 gene alleles into the rear knee joints of C57BL/6 mice. micro-CT analysis was applied to determine changes in bone morphology and density. IHC, flow cytometry, ELISA and real-time PCR were used to investigate disease progression and cytokine alterations in the course of adenoviral SAA-induced knee joint inflammation and bone destruction. Findings: The pathogenetic functions of SAA1.2, SAA1.3 and SAA1.5 protein isoforms in promoting the initiation and progression of RA were determined. We established that SAA1.2 was the most aggressive factor in RA induction and progression. Mechanistically, we found that the arthritis-inducing effect of SAA1.2 transcription in the knee joints and mutant SAA1 protein secretion in blood results in stimulation of immune responses, leading to CD8 + T cell and pro-inflammatory cytokine elevation, with subsequent synovial inflammation and bone destruction. Interpretation: These findings indicate that SAA1 protein isoforms, particularly SAA1.2, play a significant role in the induction and progression of RA and may have potential value in the early diagnosis and severity prediction for RA. Funding Statement: This work was funded by The Science and Technology Development Fund, Macau SAR (file no. FDCT-FDCT-17-002-SKL). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by the institutional committee for animal welfare.

For laparoscopic low anterior resection of the rectum, a small additional incision is needed to extract the specimen. We describe an adjustment technique, which inserted the anvil and extracted the specimen through transanal pathway.Between July 2010 and July 2012, 23 patients underwent laparoscopic rectal surgery with transanal anvil insertion and transanal prolapsing specimen extraction. All perioperative data and short-term outcomes were recorded in a database.The mean patient age was 61.3 years (range 47-68 years). Of the 23 patients, 17 underwent resection for rectal carcinoma and 6 had tubulovillous adenomas. No intraoperative complications occurred. The mean operative time was 137 minutes (range 118-170 minutes). The distal margins, circumferential resection margins, and lymph node dissections were oncologically adequate for all malignancies. One patient experienced anastomotic leakage (4.3%), treated conservatively. One male patient with benign prostatic hyperplasia suffered from postoperative urinary retention. The average postoperative hospital stay was 11.3 days (range 7-21 days). No patients experienced anal dysfunction. At a median follow-up of 26 months, there were no tumor recurrences.The technique of transanal prolapsing specimen extraction for laparoscopic low anterior resection of the rectum is feasible and safe for selected patients.

A quantitative risk assessment (QRA) based on leak detection criteria (LDC) for the design of a proposed subsea oil export pipeline is presented in this paper. The objective of this QRA/LDC study was to determine if current leak detection methodologies were sufficient, based on QRA results, while excluding the use of statistical leak detection; if not, an appropriate LDC for the leak detection system would need to be established. The famous UK PARLOC database was used for the calculation of pipeline failure rates, and the software POSVCM from MMS was used for oil spill simulations. QRA results revealed that the installation of a statistically based leak detection system (LDS) can significantly reduce time to leak detection, thereby mitigating the consequences of leakage. A sound LDC has been defined based on QRA study results and comments from various LDS vendors to assist the emergency response team (ERT) to quickly identify and locate leakage and employ the most effective measures to contain damage.

Aim The study aim was to analyse the safety and feasibility of laparoscopic intersphincteric resection with stapled coloanal anastomosis for low rectal cancer. Method Between March 2009 and August 2010, 22 patients underwent laparoscopic intersphincteric resection with a stapled coloanal anastomosis without a diverting ileostomy. The results were compared retrospectively with hand-sewn coloanal anastomoses performed between January 2001 and May 2009, which included 55 open and 38 laparoscopic intersphincteric resections. The morbidity comparison only included data relevant to the anastomosis. Function was compared using the Saito function questionnaire and the Wexner score and only involved data relevant to the laparoscopy. Results The anastomotic complication rates were similar for fistula, bleeding and neorectal mucosal prolapse (P = 0.526, P = 0.653 and P = 0.411, respectively). Anastomotic leakage and stricture formation of the stapled coloanal anastomosis were significantly lower than those of the hand-sewn coloanal anastomosis (P = 0.037 and P = 0.028, respectively). There were no significant differences in the Saito function questionnaire and the Wexner score between the stapled and hand-sewn coloanal anastomotic groups (all P > 0.05). Conclusion Laparoscopic intersphincteric resection with a stapled coloanal anastomosis is technically feasible and is less likely to result in anastomotic leakage and stricture formation than a hand-sewn anastomosis.

A QRA based LDC design for a proposed sub-sea oil export pipeline is presented in this paper as an example to reveal how to perform the QRA/LDC study in practical projects. The authors are now dedicated to a pipeline QRA/RBI program development, which will be issued in the near future. The object of QRA/LDC study is to determine if the current leak detection philosophy excluding the use of statistical leak detection is sufficient, based on QRA results; if not, an appropriate LDC will be established. The QRA assessment will determine the frequency of leaks, leak volume, response time and Shoreline/Marine Park infected oil quantity. All of the risk assessments in this paper have been done for the comparison of two scenarios: with LDS and without LDS, in order to find out the benefits of statistical LDS installation. And the result has revealed that the use of statistical LDS can largely reduce the oil spill volume. Thus, a suitable LDS is recommended to be installed to reduce the impact of oil spill consequences. A sound LDC has been defined based on QRA study results and comments form various LDS vendors in this paper to assist the Emergency Response Team (ERT) to quickly identify, locate and employ a mitigation measure to contain the damage in case a leak incident occurs.