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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.

The application of artificial intelligence in the field of primary health care can effectively improve diagnosis and treatment,avoid over-examination and over-medication,and make up for the shortage of high-quality medical resources in primary medical and health institutions.Focusing on the application of artificial intelligence in the field of primary health care,this paper analyzes the existing application modes and typical cases,studies its main stakeholders,interest demands and problems,and provides corresponding suggestions.

Early growth response proteins (EGRs), a transcriptional regulatory family comprised of EGR1, EGR2, EGR3, and EGR 4, are reportedly involved in a vast array of functions. However, EGRs, as a whole, are rarely studied in breast cancer cases. This research was performed based on public datasets. The results demonstrated that, except EGR4, the other EGRs were differentially expressed genes in breast cancer. Subsequently, this study determined the prognosis significance of the EGR family, higher expression levels of EGRs indicating better overall survival (OS) and disease-free survival (DFS), except EGR4. So we attempted to explore the potential mechanism behind the prognostic value of EGRs. At the DNA level, however, neither DNA methylation status nor genetic alterations of EGRs contributed to the prognosis significance. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that EGRs were involved in several immune-related functions. Afterward, we assessed the correlation between EGRs and the immune system before establishing a risk prediction model with a 14-gene immune signature associated with EGRs, a prognostic nomogram predicting individuals’ 1-, 3-, and 5-year survival probabilities. The risk score was an independent prognosis predictor in the breast cancer cohorts. This study evidenced EGRs’ significance for tumor immunity, demonstrating that the EGR family may be a potential immunotherapeutic target for breast cancer. The 14-gene immune signature is a promising prognostic biomarker in breast cancer.

To investigate the effect and safety of the 3-week paclitaxel liposome protocol in the treatment of castration-resistant prostate cancer (CRPC).This retrospective study included 40 cases of CRPC treated by the 3-week paclitaxel liposome protocol from February 2014 to February 2019, which involved intravenous injection of 10 mg dexamethasone in 100 ml normal saline on the first day and that of metoclopramide and panxi tora azole on the second day, followed by about 3 hours of intravenous drip of paclitaxel liposome at 135 mg/m2 for a course of 3 weeks. During the follow-up period, the patients received detection of the serum PSA level before treatment and chest x-ray and whole-body bone scan every six months. After two courses of treatment, the patients were observed for the changes in the serum PSA level, relief of bone pain, quality of survival, overall survival rate, overall survival time and toxic reactions. The protocol was continued unless the patient underwent progression, refused for unacceptable toxicity, or died.The patients were aged 59 to 79 (mean 68.80±5.67) years old, with the serum PSA level of (28.05 ± 3.22) μg/L at the baseline and (4.12 ± 0.23) μg/L after treatment. Thirty-eight of the patients were followed up for 3 to 33 (mean 12.2) months. PSA-based evaluation showed therapeutic effectiveness in 14 cases (35%), stable condition in 21 (52.5 %) and progression in 5 (12.5 %). Of the 18 patients with bone metastasis and pain, 16 (88.9 %) experienced relief of the symptoms and reduced the use of painkillers, with the bone pain scores of 5.20 ± 1.22 vs 2.79 ± 0.57 before and after treatment. By the end of the follow-up, the overall survival rate was 55.0% (22/40) and the median survival time was 17 months (95% CI: 13.4－24.6). During the treatment, no obvious adverse reactions were observed except for anemia in 1 case and hair loss in another.For the treatment of CRPC in China, the 3-week paclitaxel liposome protocol has the advantages of desirable safety, low toxicity, acceptable drug tolerance and improved quality of survival, but its curative effect needs to be verified with more randomized clinical trials with larger samples and longer follow-ups.

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 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 Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development. Purpose This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC). Methods MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model. Results Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle. Conclusion Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC.

Background: Belonging to the protein disulfide isomerase (PDI) family, anterior gradient 2 (AGR2) is overexpressed in mucus-secreting cells and endocrine organs such as breast, lung, and ovarian, but its exact function and regulation remain unclear. We aimed to perform integrative analysis of AGR2 in breast cancer.Methods: In our study, a serious of bioinformatic online databases were used to analyze the expression, regulation, prognostic value, and function of AGR2 in breast cancer.Results: The results suggested that AGR2 mRNA was overexpressed in non-basal-like or non-triple-negative breast cancer, but underexpressed in basal-like/ triple-negative breast cancer. AGR2 mRNA expression was correlated with its protein expression. Moreover, the expression of AGR2 was lower in more malignant breast cancer. Furthermore, we also found that DNA methylation, rather than copy number variation, led to AGR2 mRNA overexpression. Prognosis analysis showed no significant correlation between AGR2 level and survival, but in subtype investigation, patients with higher AGR2 level had a significantly better outcome in patients with basal-like / triple-negative breast cancer. Enrichment analysis for co-expression genes of AGR2 revealed that gene sets enriched for chromosome segregation, DNA conformation change, chromosomal region, and GABA receptor activity may play important roles in breast cancer, and that the most significant pathway was “ribosome biogenesis in eukaryotes”, in which negative co-expression genes of AGR2 were enriched.Conclusions: Overexpression of AGR2 was found in less malignant breast cancer, for the first time, our results propose that DNA methylation rather than copy number variation leads to AGR2 overexpression, which can predict favorable prognosis in basal-like/ triple-negative breast cancer, and AGR2 could be a possible regulator of ribosome biogenesis in patients with breast cancer.

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.

Long noncoding RNAs (lncRNAs) are found to be aberrantly expressed and pose significant impacts in colorectal cancer (CRC), the most prevalent type malignancy in the gastrointestinal tract. This study aimed to find out the regulation of lncRNA EIF3J antisense RNA 1 (EIF3J-AS1) on CRC progression. Expressions of EIF3J-AS1, microRNA-3163 (miR-3163), and Yes-associated protein 1 (YAP1) in tissues and cells were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Association of EIF3J-AS1 with CRC prognosis was analyzed through the online bioinformatics tool GEPIA. The biological function of EIF3J-AS1 in CRC was investigated by Cell Counting Kit-8, colony formation, caspase-3 activity, and TUNEL staining. Competitive endogenous RNA (ceRNA) network of EIF3J-AS1/miR-3163/YAP1 was determined by luciferase reporter and RNA immunoprecipitation assays. Results showed that EIF3J-AS1 was upregulated in CRC tissues and cell lines, indicating poor prognosis of CRC patients. The silence of EIF3J-AS1 led to reduced proliferation and facilitated apoptosis of CRC cells. Mechanistcally, EIF3J-AS1 was upregulated by cAMP-response element-binding protein-binding protein-mediated histone H3 on lysine 27 acetylation (H3K27ac) at the promoter region, and EIF3J-AS1 upregulated YAP1 expression through sponging miR-3163 in CRC cells. In conclusion, we first found that H3K27 acetylation-induced lncRNA EIF3J-AS1 improved proliferation and impeded apoptosis of colorectal cancer through the miR-3163/YAP1 axis, which might potentially provide a novel molecular-targeted strategy for CRC treatment.

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.

Artemisinin is a preferred medicine in the treatment of malaria. In this study, AaCMK, a key gene involved in the upstream pathway of artemisinin biosynthesis, was cloned and characterized from Artemisia annua for the first time. The full-length cDNA of AaCMK was 1 462 bp and contained an ORF of 1 197 bp that encoded a 399-anomo-acid polypeptide. Tissue expression pattern analysis showed that AaCMK was expressed in leaves, flowers, roots and stems, but with higher expression level in glandular secretory trichomes. In addition, the expression of AaCMK was markedly increased after MeJA treatment. Subcellular localization showed that the protein encoded by AaCMK was localized in chloroplast. Overexpression of AaCMK in Arabidopsis increased the contents of chlorophyll a, chlorophyll b and carotenoids. These results suggest that AaCMK plays an important role in the biosynthesis of terpenoids in A. annua and this research provids a candidate gene that could be used for engineering the artemisinin biosynthesis.

δ-Catenin is the only member of the p120 catenin (p120ctn) subfamily whose normal pattern of expression is restricted to the brain. Similar to p120ctn, δ-catenin can bind to the juxtamembrane domain of E-cadherin. We examined the expression of δ-catenin, p120ctn, and E-cadherin using immunohistochemistry in 95 cases of colorectal cancer (CRC) and 15 normal colon tissues. Co-immunoprecipitation was used to examine whether δ-catenin competed with p120ctn to bind E-cadherin in CRC cells. The effects of δ-catenin overexpression or siRNA-mediated knockdown on the proliferation and invasive ability of CRC cells were investigated using the MTT and Matrigel invasion assays. The results showed that positive δ-catenin expression was significantly more frequent in CRC compared to normal colon tissues and associated with poor differentiation, stage III–IV disease, and lymph node metastasis in CRC (all P

In this report, a strains of nitrifying bacteria HFX08 with low temperature and low carbon nitrogen ratio is separated from the activated sludge which is domesticated of the northern city sewage plant in winter. The optimum carbon source for the growth of the strain is sodium acetate, the source of nitrogen is potassium nitrate and the optimum growth temperature range is 10-20°C correspondingly.

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.