[COL11A1 regulates PI3K/Akt/GSK-3ß pathway and promotes human lung adenocarcinoma primary cell migration and invasion].

Objective: To investigate the role and mechanism of COL11A1 in lung adenocarcinoma migration and invasion. Methods: Surgical pathological tissues of 4 patients with lung adenocarcinoma admitted to the Affiliated Hospital of Guizhou Medical University from September to November 2020 were used. Immunohistochemical methods were used to identify lung adenocarcinoma tissues, para-cancerous tissues and parallel transcriptome sequencing. Genetic prognostic analysis was conducted by TCGA and GTEx databases.The expression level of COL11A1 gene in lung adenocarcinoma and adjacent tissues was detected by Western blotting.The primary human lung adenocarcinoma cells cultured. The COL11A1 siRNA was transfected into primary human lung adenocarcinoma cells, then the transcriptome sequencing of differential genes was performed,and KEGG enrichment analysis of differential gene enrichment pathway was conducted. Protein expression and phosphorylation were detected by Western blot method. Cell migration was detected by scratch healing test. Cell proliferation was detected by CCK8 method and invasion ability was detected by Transwell method. Results: Ten differentially expressed genes were screened by transcription sequencing in lung adenocarcinoma. Prognostic analysis of single gene showed that COL11A1 gene expression level was correlated with survival rate (P<0.001). The expression of COL11A1 in lung adenocarcinoma was higher than that in adjacent tissues by Western blot (P<0.001). Transcriptome sequencing of COL11A1 siRNA transfection into primary human lung adenocarcinoma cells showed that differential genes were concentrated in PI3K-akt pathway. The expression of tumor suppressor gene PTEN in siRNA transfection group was significantly higher than that in control group and negative transfection group by Western blot. The expression of Aktp-Akt 473 p-Akt 308 p-PTENp-PDK1p-c-Rafp-GSK-3 ß was down-regulated (all P<0.05).Compared with the negative control group, the ability of migration, proliferation and invasion of primary human lung adenocarcinoma cells in siRNA transfection group decreased (all P<0.05). COL11A1 regulates PI3K/Akt/GSK-3 ß pathway to promote migration and invasion of primary human lung adenocarcinoma cells. Conclusion: COL11A1 regulates PI3K/Akt/GSK-3 ß pathway to promote migration and invasion of primary human lung adenocarcinoma cells.

A Scoping Review of Student Pharmacist-Led Transitions-of-Care Initiatives.

OBJECTIVES: To identify and evaluate the current literature pertaining to student pharmacist-led transitions-of-care (TOC) initiatives and to inform pharmacy educators regarding the current and future roles of pharmacy learners in TOC. FINDINGS: A total of 14 articles were identified describing student-led initiatives in care transitions to the inpatient setting and from the inpatient to the outpatient setting. In most studies, student pharmacists involved in delivering TOC services were completing either an advanced pharmacy practice experience or an introductory pharmacy practice experience and were most commonly performing services such as admission medication history and reconciliation. The studies evaluated the impact of student-led TOC services through the identification or resolution of medication-related problems, interventions, and/or discrepancies and included limited and conflicting results pertaining to patient care-based outcomes. SUMMARY: Student pharmacists are involved in delivering and leading a variety of TOC services in the inpatient setting and postdischarge period. These student-led TOC initiatives not only provide added value to patient care and the health system but also enhance students' preparation and readiness for pharmacy practice. Colleges and schools of pharmacy should incorporate learning experiences into the curriculum that equip students to contribute to TOC efforts and promote continuity of care across the health system.

Mass Measurement of Upper fp-Shell N=Z-2 and N=Z-1 Nuclei and the Importance of Three-Nucleon Force along the N=Z Line.

Using a novel method of isochronous mass spectrometry, the masses of ^{62}Ge, ^{64}As, ^{66}Se, and ^{70}Kr are measured for the first time, and the masses of ^{58}Zn, ^{61}Ga, ^{63}Ge, ^{65}As, ^{67}Se, ^{71}Kr, and ^{75}Sr are redetermined with improved accuracy. The new masses allow us to derive residual proton-neutron interactions (δV_{pn}) in the N=Z nuclei, which are found to decrease (increase) with increasing mass A for even-even (odd-odd) nuclei beyond Z=28. This bifurcation of δV_{pn} cannot be reproduced by the available mass models, nor is it consistent with expectations of a pseudo-SU(4) symmetry restoration in the fp shell. We performed ab initio calculations with a chiral three-nucleon force (3NF) included, which indicate the enhancement of the T=1 pn pairing over the T=0 pn pairing in this mass region, leading to the opposite evolving trends of δV_{pn} in even-even and odd-odd nuclei.

Risk factors of involuntary referral by police to ER psychiatric services for patients with a severe mental illness: A GEE analysis.

This study aimed to identify risk factors for involuntary referral by police to emergency room (ER) psychiatric services for community-based patients with a mental illness via a generalized estimating equation (GEE) analysis. The analysis was based on data from the Management Information System of Psychiatric Care (MISPC) system for patients with a severe mental illness in Taipei, Taiwan and registered referral records of the police. Data on 6378 patients aged ≥20 years were used in this study, including 164 patients who were involuntarily referred to the ER by the police and 6214 patients who were not during the period of January 1, 2018 to December 31, 2020. GEEs were utilized to explore possible risk factors of repeated involuntary referral to ER psychiatric services for patients with a severe mental illness. The logistic regressions indicated that patients defined as "severe" according to the Mental Health Act of Taiwan (crude odds ratio (OR): 3.840, 95 % confidence interval (CI): 2.407-6.126), with a disability (crude OR: 3.567, 95 % CI: 1.339-9.501), with two or more family members with a psychiatric disorder (crude OR: 1.598, 95 % CI: 1.002-2.548), with a history of a suicide attempt (crude OR: 25.582, 95 % CI: 17.608-37.167), and with a history of domestic violence (crude OR: 16.141, 95 % CI: 11.539-22.579) were positively associated with involuntary referral to ER psychiatric services. However, age (crude OR: 0.971, 95 % CI: 0.960-0.983) and the MISPC score (crude OR: 0.834, 95 % CI: 0.800-0.869) were inversely associated with involuntary referral to ER psychiatric services. After adjusting for demographics and potential confounders, we found that patients defined as "severe" (Exp (ß): 3.236), with a disability (Exp (ß): 3.715), with a history of a suicide attempt (Exp (ß): 8.706), and with a history of domestic violence (Exp (ß): 8.826), as well as age (Exp (ß): 0.986) and the MISPC score (Exp (ß): 0.902) remained significantly associated with repeated involuntary referral to ER psychiatric services. In conclusion, community-based mentally ill patients with a history of a suicide attempt, with a history of domestic violence, with a severe illness, and with a profound level of disability were highly associated with involuntary referral to ER psychiatric services. We suggest that community mental health case managers identify significant factors associated with involuntary referral to ER psychiatric services to accordingly arrange case management plans.

A Programmatic Approach to Peer-Led Tutoring to Assist Students in Academic Difficulty.

Objective. To evaluate a peer-led tutoring program to assist students in academic difficulty in the didactic curriculum across multiple courses using one-on-one and large group peer-led sessions, and to evaluate the academic performance and perceptions of students in this program.Methods. This study involved first-year (P1) through fourth-year (P4) pharmacy students who served as tutors and their P1 through P3 tutees. Tutoring was offered in multiple didactic courses using one-on-one and large group peer-led sessions. Didactic curriculum completion rates and perceptions of the program were assessed.Results. A total of 463 (47%) P1 through P3 student pharmacists used the one-on-one or large group peer-led tutoring services in 28 courses across four academic years. Tutored students had a lower grade distribution compared to nontutored students, suggesting a more at-risk group for academic failures and dismissals. Despite this, the didactic curriculum completion rate was comparable between the tutored and nontutored students during the study period, suggesting that the program helped reduce academic dismissals of the at-risk tutored students. On the perceptions survey, 95% of respondents felt they improved their study habits, and 92% felt more confident in their ability to succeed.Conclusion. This peer-led tutoring program appeared to be successful in providing comparable didactic curriculum completion rates of tutored students, who represented an at-risk group for academic failures and dismissals compared with nontutored students. The tutoring program structure and design may be a useful tool for other colleges of pharmacy as they seek ways to assist students.

The association between sociodemographic status and COPD and asthma mortality, DALY and YLD in southern China, 2005-2015.

BACKGROUND: Little is known about the disease burden of chronic obstructive pulmonary disease (COPD) and asthma in southern China. METHOD: We calculated the mortality, disability-adjusted life-years (DALY), years lived with disability (YLD) and years of life lost (YLL) for COPD and asthma in Guangdong province between 2005 and 2015. We examined the significance of trends of mortality, DALY, YLD and YLL rates for COPD and asthma with the Cochran-Armitage trend test. We also analyzed their association with sociodemographic factors by negative binomial models. RESULT: The age-standardized mortality, DALY, YLD and YLL rates of COPD and asthma decreased significantly in Guangdong, except for an increase of 11.3% in the age-standardized YLD rate of COPD between 2005 and 2015 (all P < 0.05). Compared with females, the respective adjusted mortality rate ratio of males was 2.11 for COPD, and 0.74 for asthma. Compared with other regions, the richest region, Pearl River Delta, had the lowest mortality, DALY, YLD and YLL rate ratios (RR) of COPD and asthma (all P < 0.05). COPD and asthma mortality, DALY, YLD and YLL rates increased substantially with age. Specifically, when compared with the 25-49 years age group, the respective adjusted DALY RR of asthma was 1.91, 2.02 and 22.21 for 0-24, 50-74 and ≥75 years age group; the respective adjusted YLD RR was 2.27, 1.33 and 7.17 for 0-24, 50-74 and ≥75 years age group. CONCLUSIONS: Disease burden of COPD and asthma decreased in Guangdong province in southern China between 2005 and 2015; however, a disproportionate burden of COPD and asthma in terms of age, sex and regions was observed. The relatively high disease burden and high rate of impaired public health from the less developed regions highlight the need for focused policy making to address the problem.

Photosynthesis in response to salinity and submergence in two Rhizophoraceae mangroves adapted to different tidal elevations.

Mangrove ecosystems are vulnerable to rising sea levels. When the sea level rises, the plants are exposed to increased salinity and tidal submergence. In Taiwan, the mangrove species Kandelia obovata and Rhizophora stylosa grow in different habitats and at different elevations. To understand the response of photosynthesis to salinity and submergence in mangroves adapted to different tidal elevations, gas exchange and chlorophyll fluorescence parameters were measured in K. obovata and R. stylosa under different salinity (20 and 40‰) and submergence treatments. The period of light induction of photosynthesis for the two mangrove species was >60 min. In the induction process, the increase in photosystem efficiency was faster than the increase in stomatal opening, but CO2 fixation efficiency was restricted by stomatal conductance. The constraint of stomatal opening speed is related to the conservative water-use strategy developed in response to mangrove environments. Submergence increased the photosynthetic rate of K. obovata, but not that of R. stylosa. Although R. stylosa was more salt tolerant than K. obovata, R. stylosa was not submergence tolerant in a high-salinity environment, which may be the reason for the higher intertidal elevations observed for R. stylosa in comparison with K. obovata. The photosynthetic rate and energy-dependent quenching (qE) of the two mangroves presented a negative relationship with photoinhibition, and high-salt treatment simultaneously reduced photosynthetic rate and qE. A decrease in the photosynthetic rate increased excess energy, whereas a decrease in qE decreased photoprotection; both increased photoinhibition. As the degree of photoinhibition can be easily measured in the field, it is a useful ecological monitoring index that provides a suitable reference for mangrove restoration, habitat construction and ecological monitoring.

Ephedrine causes liver toxicity in SD rats via oxidative stress and inflammatory responses.

Ephedrine abuse has spread in many parts of the world and severely threatens human health. The mechanism of ephedrine-induced toxicity still remains unclear. This study was performed to investigate the effects of ephedrine treatment on the liver and explore the underlying mechanisms. Sprague Dawley rats were divided into saline and ephedrine groups. Rats were treated with ephedrine at 20 mg/kg or 40 mg/kg (n = 10) by oral gavage daily for 7 days. Pathological changes were examined by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay. Enzyme-linked immunosorbent assays were used to measure the liver functional markers, oxidative stress markers, and inflammatory cytokines. Real-time polymerase chain reaction and Western blot were used to measure gene and protein expression, respectively. Our data showed that ephedrine treatment increased hepatocellular cell apoptosis and impaired liver function. Moreover, ephedrine treatment increased oxidative stress and inflammatory responses, which may be due to the increase of transforming growth factor ß (TGF-ß)/Smad3 expression. Our study demonstrated that short-term treatment of ephedrine caused liver toxicity in rats through regulating TGF-ß/Smad pathway.

ROR1-AS1 promotes tumorigenesis of colorectal cancer via targeting Wnt/ß-catenin.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "ROR1-AS1 promotes tumorigenesis of colorectal cancer via targeting Wnt/ß-catenin, by T. Liao, S.-L.-M. Maierdan, C. Lv, published in Eur Rev Med Pharmacol Sci 2019; 23 (3 Suppl): 217-223-DOI: 10.26355/eurrev_201908_18650-PMID: 31389604" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18650.

Pharmacogenomics in Asian Subpopulations and Impacts on Commonly Prescribed Medications.

Asians as a group comprise > 60% the world's population. There is an incredible amount of diversity in Asian and admixed populations that has not been addressed in a pharmacogenetic context. The known pharmacogenetic differences in Asian subgroups generally represent previously known variants that are present at much lower or higher frequencies in Asians compared with other populations. In this review we summarize the main drugs and known genes that appear to have differences in their pharmacogenetic properties in certain Asian populations. Evidence-based guidelines and summary statistics from the US Food and Drug Administration and the Clinical Pharmacogenetics Implementation Consortium were analyzed for ethnic differences in outcomes. Implicated drugs included commonly prescribed drugs such as warfarin, clopidogrel, carbamazepine, and allopurinol. The majority of these associations are due to Asians more commonly being poor metabolizers of cytochrome P450 (CYP) 2C19 and carriers of the human leukocyte antigen (HLA)-B*15:02 allele. The relative risk increase was shown to vary between genes and drugs, but could be > 100-fold higher in Asians. Specifically, there was a 172-fold increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis with carbamazepine use among HLA-B*15:02 carriers. The effects ranged from relatively benign reactions such as reduced drug efficacy to severe cutaneous skin reactions. These reactions are severe and prevalent enough to warrant pharmacogenetic testing and appropriate changes in dose and medication choice for at-risk populations. Further studies should be done on Asian cohorts to more fully understand pharmacogenetic variants in these populations and to clarify how such differences may influence drug response.

Implementation and evaluation of problem-based video podcasts in an introductory pharmacokinetics course.

INTRODUCTION: The use of problem-based video podcasts in health sciences education is limited. Principles of Pharmacokinetics is an introductory course that establishes a foundation for understanding pharmacokinetic concepts. The primary objective was to determine the impact of problem-based video podcasts in an introductory pharmacokinetics course on student learning. METHODS: Problem-based video podcasts were implemented in an introductory pharmacokinetics course in spring 2015. Student pharmacists in the first professional year enrolled in the course during spring 2015, 2016, and 2017 were included in the study with students enrolled in the course in spring 2014 serving as the control group. The primary outcome was the impact of problem-based video podcasts on student learning as assessed by student performance on the final exam. Other outcomes included student utilization of the video podcasts, overall course grades, and student perceptions of learning using video podcasts. RESULTS: A total of 633 students in four academic years were included for analysis. Final exam scores were significantly higher in spring 2015 and 2016 compared to 2014. The 2017 final exam scores were similar to the final exam scores in 2014. Students perceived the problem-based video podcasts enhanced their ability to apply concepts to a patient case, reinforced concepts from lectures, and improved their understanding of clinical pharmacokinetics. CONCLUSION: The use of problem-based video podcasts is an innovative method to augment learning outside of the traditional class time and may enhance learning without replacing direct instructor-student contact. Students reported the video podcasts improved their understanding of clinical pharmacokinetics.

Research on multi-agent genetic algorithm based on tabu search for the job shop scheduling problem.

The solution to the job shop scheduling problem (JSSP) is of great significance for improving resource utilization and production efficiency of enterprises. In this paper, in view of its non-deterministic polynomial properties, a multi-agent genetic algorithm based on tabu search (MAGATS) is proposed to solve JSSPs under makespan constraints. Firstly, a multi-agent genetic algorithm (MAGA) is proposed. During the process, a multi-agent grid environment is constructed based on characteristics of multi-agent systems and genetic algorithm (GA), and a corresponding neighbor interaction operator, a mutation operator based on neighborhood structure and a self-learning operator are designed. Then, combining tabu search algorithm with a MAGA, the algorithm MAGATS are presented. Finally, 43 benchmark instances are tested with the new algorithm. Compared with four other algorithms, the optimization performance of it is analyzed based on obtained test results. Effectiveness of the new algorithm is verified by analysis results.

Liraglutide protects from renal damage via Akt-mTOR pathway in rats with diabetic kidney disease.

OBJECTIVE: To explore the protective effect of liraglutide on renal damage in rats with diabetic kidney disease (DKD) through the protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. MATERIALS AND METHODS: A total of 45 specific pathogen-free male Sprague-Dawley rats were divided into healthy group (no diabetes, n=15), diabetes group (diabetes, n=15), and liraglutide group (diabetes + liraglutide intervention, n=15). The differences in the biochemical indexes, lesion degree, glomerular Nephrin expression level, and mRNA and protein expressions of Akt-mTOR in renal tissues were detected in three groups via hematoxylin-eosin (HE) staining, immunohistochemistry, Western blotting, and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), respectively. RESULTS: The albumin-to-creatinine ratio (ACR) and levels of serum creatinine (Scr), urine microalbumin (UmAlb), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in renal tissues were the lowest in healthy group and the highest in diabetes group, while they significantly declined in liraglutide group compared with those in diabetes group. Also, there were statistically significant differences (p<0.05). The level of high-density lipoprotein cholesterol (HDL-C) in renal tissues was the highest in healthy group and the lowest in diabetes group, while it was significantly increased in liraglutide group compared with that in diabetes group. Also, there were statistically significant differences (p<0.05). In healthy group, the mesangial structure and renal tubules were normal, the tubular basement membrane was smooth and intact, and there were no interstitial widening and inflammatory cell infiltration. Compared with diabetes group, the mesangial cell proliferation and vacuolar degeneration were alleviated, while the tubular dilatation or atrophy, fibrous tissues, and inflammatory cells were reduced in liraglutide group. Moreover, the results of immunohistochemical staining revealed that the glomerular Nephrin protein was arranged uniformly and showed the blue-black particles in healthy group. The glomerular Nephrin protein expressed was significantly decreased and arranged disorderly in diabetes group compared with that in healthy group, while it was increased in liraglutide group compared with that in diabetes group (p<0.05). The protein expression of Akt-mTOR in renal tissues was the lowest in healthy group and the highest in diabetes group, while it markedly declined in liraglutide group compared with that in diabetes group, displaying statistically significant differences (p<0.05). Similarly, the mRNA expression of Akt-mTOR in renal tissues was the lowest in healthy group and the highest in diabetes group, while it markedly declined in liraglutide group compared with that in diabetes group, displaying also statistically significant differences (p<0.05). CONCLUSIONS: Liraglutide can significantly reduce the blood glucose and improve the renal function in rats by suppressing the protein expression of AKT-mTOR, thereby exerting a protective effect on renal damage in rats with DKD.

ROR1-AS1 promotes tumorigenesis of colorectal cancer via targeting Wnt/ß-catenin.

OBJECTIVE: Recent studies have discovered that long noncoding RNAs (lncRNAs) play an important role in malignant tumors. In this research, lncRNA ROR1-AS1 was selected to identify how it affected the development of colorectal cancer (CRC). PATIENTS AND METHODS: ROR1-AS1 expression was detected by Real-time quantitative polymerase chain reaction (RT-qPCR) in CRC tissue samples. ROR1-AS1 expression level and patients' overall survival time were analyzed. Functional experiments were conducted to identify the changes of biological behaviors in CRC cells after knockdown of ROR1-AS1. Moreover, we also explored the underlying mechanism. RESULTS: Detection of ROR1-AS1 expression level in patients' tissues showed that ROR1-AS1 was higher in CRC tissues than that in adjacent ones. ROR1-AS1 expression was negatively associated with patients' overall survival time. Cell growth ability was inhibited due to knockdown of ROR1-AS1 in vitro. Moreover, cell migration and invasion abilities were repressed after ROR1-AS1 was knockdown. Furthermore, due to the knockdown of ROR1-AS1, the targeted proteins in Wnt/ß-catenin signaling pathway were suppressed. CONCLUSIONS: These results suggested that ROR1-AS1 could enhance cell metastasis and proliferation via inducing Wnt/ß-catenin signaling pathway, which might offer a potential therapeutic target in CRC.

Study on molecular mechanism of MiRNA-29a in promoting proliferation and invasion of non-small-cell lung cancer by inhibiting MTSS1.

OBJECTIVE: To investigate the biological role of micro-ribonucleic acid (miR)-29a in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: 55 cases of NSCLC tissue specimens and paired normal lung tissue specimens collected in the Department II of Oncology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from July 2012 to April 2015 were randomly included. The fluorescent quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect the expression levels of miR-29a and metastasis suppressor 1 (MTSS1). Pearson correlation analysis was utilized to investigate the relationship between miR-29a expression and MTSS1 expression in NSCLC tissues, and the Kaplan-Meier survival curves were constructed to analyze the association of miR-29a expression with the survival time of NSCLC patients. A54 proliferation and invasion abilities were measured by means of plate clone formation assay, and transwell assay after the miR-29a was suppressed by miRNA inhibitor. Luciferase assay was used to detect the target gene of miR-29a. RESULTS: In NSCLC tissues, the miR-29a expression level was higher than that in normal lung tissues (p<0.05), while the expression level of MTSS1 protein was remarkably lower than that in normal lung tissues (p<0.05). The median survival time of the patients was 15.1 months in high miR-29a expression group and 18.3 months in low miR-29a expression group (p<0.05). The miR-29a expression was negatively correlated with the expression level of MTSS1 protein in NSCLC tissues (r=-0.762, p<0.05). Luciferase results suggest that miR-29a binds to the promoter region of MTSS1 and inhibits its transcription level. The expression of MTSS1 protein was up-regulated notably after miR-29a knockdown by an inhibitor. It was revealed in the results of transwell assay and plate clone formation assay that the proliferative and invasive capacity of A549 cells was significantly decreased after knockdown of miR-29a. CONCLUSIONS: The transcribed miR-29a down-regulates the protein level of MTSS1, suppressor of tumor proliferation and invasion, thereby promoting the proliferative and invasive capacity of NSCLC cells. Both miR-29a and MTSS1 are expected to become potential therapeutic targets for NSCLC.

Dose-dependent cytotoxicity evaluation of graphite nanoparticles for diamond-like carbon film application on artificial joints.

While a diamond-like carbon (DLC)-coated joint prosthesis represents the implant of choice for total hip replacement in patients, it also leads to concern due to the cytotoxicity of wear debris in the form of graphite nanoparticles (GNs), ultimately limiting its clinical use. In this study, the cytotoxicity of various GN doses was evaluated. Mouse macrophages and osteoblasts were incubated with GNs (<30 nm diameter), followed by evaluation of cytotoxicity by means of assessing inflammatory cytokines, results of alkaline phosphatase assays, and related signaling protein expression. Cytotoxicity evaluation showed that cell viability decreased in a dose-dependent manner (10-100 µg ml-1), and steeply declined at GNs concentrations greater than 30 µg ml-1. Noticeable cytotoxicity was observed as the GN dose exceeded this threshold due to upregulated receptor of activator of nuclear factor kB-ligand expression and downregulated osteoprotegerin expression. Meanwhile, activated macrophage morphology was observed as a result of the intense inflammatory response caused by the high doses of GNs (>30 µg ml-1), as observed by the increased release of TNF-α and IL-6. The results suggest that GNs had a significant dose-dependent cytotoxicity in vitro, with a lethal dose of 30 µg ml-1 leading to dramatic increases in cytotoxicity. Our GN cytotoxicity evaluation indicates a safe level for wear debris-related arthropathy and could propel the clinical application of DLC-coated total hip prostheses.

Evaluation of the Size-Dependent Cytotoxicity of DLC (Diamondlike Carbon) Wear Debris in Arthroplasty Applications.

Patients with DLC (diamond like carbon)-coated artificial joints may be exposed to a wide size range of DLC wear debris (DW). In this study, the cytotoxicity of DW of different size ranges (0-0.22, 0.22-0.65, 0.65-1.0, and 1.0-5.0 µm) was evaluated. The microstructure and physical characteristics of DW were investigated by Raman spectroscopy, transmission electron microscopy (TEM), scanning electron microscope (SEM), and dynamic light scattering (DLS). Macrophages, osteoblasts, and fibroblasts were incubated with DW of different size ranges respectively followed by cytotoxicity evaluations of inflammatory cytokines, alkaline phosphatase (ALP) assays, and related signal protein expression analysis. The results showed that, except for the size range of 0-0.22 µm, DW cytotoxicity showed a size-dependent (0.22-5.0 µm) decrease with increasing size. Within the range of 0.22-5.0 µm, DW of larger size resulted in lessened inflammatory response and enhanced osteoblastogenesis and fibrogenesis, with increased viability of cells (macrophages, osteoblasts, and fibroblasts), better morphology, less release of pro-inflammatory factors and more release of anti-inflammatory factors. The results demonstrated that DW sizes below 0.22 µm had less negative effects on cell adhesion and growth because of the BSA (bovine serum albumin) encapsulation effect. These findings provide valuable knowledge about the comprehensive mechanism of promotion of inflammatory response and inhibition of osteoblastogenesis and fibrogenesis induced by DW. In conclusion, an effective system of biocompatibility evaluation for different sizes of DW was derived.

Biological responses of diamond-like carbon (DLC) films with different structures in biomedical application.

Diamond-like carbon (DLC) films are potential candidates for artificial joint surface modification in biomedical applications, and the influence of the structural features of DLC surfaces on cell functions has attracted attention in recent decades. Here, the biocompatibility of DLC films with different structures was investigated using macrophages, osteoblasts and fibroblasts. The results showed that DLC films with a low ratio of sp(2)/sp(3), which tend to have a structure similar to that of diamond, led to less inflammatory, excellent osteogenic and fibroblastic reactions, with higher cell viability, better morphology, lower release of TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6), and higher release of IL-10 (interleukin-10). The results also demonstrated that the high-density diamond structure (low ratio of sp(2)/sp(3)) of DLC films is beneficial for cell adhesion and growth because of better protein adsorption without electrostatic repulsion. These findings provide valuable insights into the mechanisms underlying inhibition of an inflammatory response and the promotion of osteoblastogenesis and fibrous propagation, and effectively build a system for evaluating the biocompatibility of DLC films.

Risk factors for cryptococcal infection among patients with rheumatoid arthritis receiving different immunosuppressive medications.

Increasing evidence indicates that the risk of cryptococcal infections is increased in patients with rheumatoid arthritis (RA). However, the association between cryptococcosis and immunosuppressive medications in RA patients is still uncertain and little is known about risk factors for cryptococcal disease among RA patients. We conducted a retrospective case-control study to investigate the epidemiology of RA patients with cryptococcosis in a medical centre during the period 2001-14. We estimated ORs with 95% CI for cryptococcosis according to co-morbidities and immunosuppressive medications by using backward stepwise logistic regression. Among 9132 newly diagnosed RA patients, 20 (0.22%) were newly diagnosed with cryptococcal infection after RA identification. All cryptococcosis cases had been receiving corticosteroid treatment for some time (3.9±3.3 years) before infection. After full adjustment, chronic kidney disease (adjusted OR (aOR) 2.72, 95% CI 1.04-7.08, p 0.041) was a significant risk factor for cryptococcosis in RA patients. Exposure to adalimumab (monoclonal anti-tumour necrosis factor (TNF) antibodies) (aOR 4.50, 95% CI 1.03-19.66, p 0.046) were significantly associated with increased risks of cryptococcosis. Time to cryptococcosis diagnosis among RA patients receiving anti-TNF biologicals was shorter than in patients not receiving anti-TNF biologicals (1.5±1.2 years versus 8.4±5.5 years, p<0.001). Among RA patients, the risk for development of cryptococcosis was higher among those who had chronic kidney disease and were receiving the monoclonal anti-TNF antibody adalimumab. Therefore, we suggest that cryptococcal infection should be suspected in RA patients with risk factors.

[Massive hemorrhage caused by fungal infections after donation-after-cardiac-death kidney transplantation: clinical features, prevention and treatment experience].

OBJECTIVE: To study the characteristics and prevention and treatment strategies of massive hemorrhage caused by fungal infections after donation-after-cardiac-death (DCD) kidney transplantation. METHODS: A total of 91 cases of DCD kidney transplantation between August 25, 2013 and June 30, 2015 in Third Affiliated Hospital of Sun Yat-sen Univservity were retrospectively analyzed. The characteristics of and prevention and treatments strategies for postoperative massive hemorrhage caused by fungal infections were summarized. RESULTS: Ninety-one cases of DCD kidney transplantation were divided into 2 groups based on regimens for preventing postoperative fungal infections: fluconazole prophylaxis group: a total of 26 cases of renal transplant before June 11, 2014 received fluconazole regimen, from postoperative day 0 to 2 weeks; micafungin prophylaxis group: a total of 65 cases of renal transplant after June 11, 2014 received micafungin regimen, also for 2 weeks from postoperative day 0. Two cases in fluconazole group developed postoperative massive hemorrhage. In case 1, the hemorrhage occurred at 2 weeks after transplantation. Graft nephrectomy was performed during surgical exploration for hemostasis, yet the massive hemorrhage relapsed 2 weeks later. Endoluminal exclusion of external iliac artery using endovascular covered stent-graft at the anastomosis site was performed and the massive bleeding was successfully stopped. The patient was restored to hemodialysis and waited for second kidney transplantation. Candia albicans was detected in the culture of blood and drainage liquid from incision. The other case of hemorrhage occurred at 3 weeks after transplantation. Graft nephrectomy plus endovascular exclusion using covered stent-graft were also performed to stop the massive bleeding. Massive fungal hyphae and spores were observed at the stump of renal graft artery under microscope. The patient received second kidney transplantation after 6 months successfully. No massive hemorrhage caused by fungal infections occurred in micafungin prophylaxis group. CONCLUSIONS: Massive hemorrhage cased by fungal infections after DCD kidney transplantation is usually characterized by delayed and recurrent course, and may result in graft nephrectomy or even death of patients. Endovascular exclusion using covered stent can successfully stop bleeding and rescue life of patients. Two-week preemptive prophylaxis of fungal infections using micafungin can effectively prevent delayed fungal massive hemorrhage in DCD kidney transplantation.