The effect of tranexamic acid on artificial joint materials: a biomechanical study (the bioTRANX study)

Background

Tranexamic acid (TXA) has been successfully used to reduce bleeding in joint replacement. Recently local TXA has been advocated to reduce blood loss in total knee or hip replacement; however, this raised concerns about potential adverse effects of TXA upon the artificial joint replacement.

Materials and methods

In this biomechanical study we compared the effects of TXA and saline upon the following biomechanical properties of artificial joint materials—(1) tensile properties (ultimate strength, stiffness and Young’s modulus), (2) the wear rate using a multi-directional pin-on-plate machine, and (3) the surface topography of pins and plates before and after wear rate testing.

Results

There were no significant differences in tensile strength, wear rates or surface topography of either ultra-high-molecular-weight polyethylene pins or cobalt chromium molybdenum metal plates between specimens soaked in TXA and specimens soaked in saline.

Conclusion

Biomechanical testing shows that there are no biomechanical adverse affects on the properties of common artificial joint materials from using topical TXA.

Level of evidence

V     

Analysis of CD8+ Treg cells in patients with ovarian cancer: a possible mechanism for immune impairment

Regulatory T (Treg) cells may participate in mediating a suppressive microenvironment that blunts successful anti-tumor immunotherapy. Recent studies show that CD8⁺ Treg cells might impede effective immune responses to established tumors. However, there is limited research regarding CD8⁺ Treg cells in ovarian cancer (OC) patients. Here, we investigated CD8⁺ Treg cells in OC patients and their in vitro induction. The immunohistochemistry of tumor-infiltrating lymphocytes revealed a significant correlation between the intratumoral CD8⁺ T cells and the forkhead box p3 (Foxp3)⁺ cells in the intraepithelial and stromal areas of advanced OC tissues. We examined the expression of Treg markers in CD8⁺ T cells from the peripheral blood and fresh tumor tissues of OC patients using flow cytometry. Our results indicated an increase in the CD8⁺ Treg cell subsets of OC patients compared with those in patients with benign ovarian tumors and healthy controls, including an increased expression of CD25, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and Foxp3 and decreased CD28 expression. To demonstrate whether the tumor microenvironment could convert CD8⁺ effector T cells into suppressor cells, we used an in vitro transwell culturing system. Compared with the CD8⁺ T cells cultured alone, the CD8⁺ Treg cells induced in vitro by coculture with SK-OV-3/A2780 showed increased CTLA-4 and Foxp3 expression and decreased CD28 expression. In addition, the in vitro-induced CD8⁺ Treg cells inhibited naïve CD4⁺ T-cell proliferation, which was partially mediated through TGF-β1 and IFN-γ. Our study suggests that CD8⁺ Treg cells were increased in OC patients and could be induced in vitro, which may be the way that tumors limit antitumor immunity and evade immune surveillance.     

Protective effect of bone marrow mesenchymal stem cells on PC12 cells apoptosis mediated by TAG1

Objective: This study aims to explore the protection effect of bone marrow mesenchymal stem cells (BMSCs) on PC12 cells apoptosis mediated by transient axonal glycoprotein 1 (TAG1). Methods: PC12 cells were divided into control group, Aβ_25-35 group and BMSCs + Aβ_25-35 group. The effects of BMSCs on PC12 cells treated by Aβ_25-35 were detected using MTT, Hoechst 33258 and Annexin V-FITC/PI staining methods. The expression levels of TAG1, β-amyloid precursor protein (APP), AICD and p53 were determined by RT-PCR and Western blotting methods. The expression levels of Bax and Bcl-2 were determined by Western blotting method. The activity of Caspase 3 was detected by spectrophotometric method. Results: MTT results showed that cell activity decreased after the treatment of 20 μM Aβ_25-35 for 48 h (P<0.01) while it increased in BMSCs + Aβ_25-35 group (P<0.01). Hoechst 33258 and Annexin V-FITC/PI staining results showed that Aβ_25-35 could induce the apoptosis of PC12 cells while the apoptosis of PC12 cells was inhibited in BMSCs + Aβ_25-35 group. RT-PCR and Western blotting methods showed that 20 μM Aβ_25-35 could increase the expression levels of TAG1, APP, AICD and p53 (P<0.01) while they decreased in BMSCs + Aβ_25-35 group (P<0.01). 20 μM Aβ_25-35 could increase the expression levels of Bax and decrease the expression levels of Bcl-2 (P<0.01), while the expression levels of Bax decreased and the expression levels of Bcl-2 increase in BMSCs + Aβ_25-35 group (P<0.01). 20 μM Aβ_25-35 could enhance Caspase 3 activity while it decreased in BMSCs + Aβ_25-35 group (P<0.01). Conclusions BMSCs with Aβ_25-35 could inhibit the apoptosis of PC12 cells, which maybe related with TAG1/APP/AICD signal pathway.     

Framingham风险评分与遗忘型轻度认知障碍的相关性

目的探讨Framingham风险评分与遗忘型轻度认知障碍（amnestic mild cognitive impairment, aMCI）的相关性,以期为阿尔茨海默症的早期预防提供有意义的临床依据。 方法选取2018年1月至2019年12月浙江医院收治的124老年人,均行神经心理学评估,其中aMCI老年人54例（aMCI组）,认知正常老年人70例（正常组）。比较两组老年人的Framingham风险评分,并分析aMCI老年人Framingham风险评分与认知功能的相关性。计量资料的组间比较采用t检验或非参数Mann-Whitney U检验,计数资料的比较采用χ²检验,Framingham风险评分与认知功能的相关性采用Spearman相关分析。 结果两组对象一般资料（包括Framingham风险评分的组成指标）的差异无统计学意义（P>0.05）。aMCI组Framingham风险评分中位数为24%,四分位数间距为22%;正常组Framingham风险评分中位数为16.7%,四分位数间距为22%;差异有统计学意义（Z=-2.721,P<0.01）。aMCI老年人Framingham风险评分与简易智能状态检查量表及听觉词语学习测验20 min延迟回忆评分均呈显著负相关（r=-0.203、-0.570,P<0.01）。 结论Framingham风险评分与老年人认知功能有关,可作为老年人认知功能障碍的预警参考指标。     

Physical activity and health outcomes in persons with haemophilia B

Regular participation in physical activity helps to prevent damage and maintain joint health in persons with haemophilia. This study describes self‐reported physical activity participation among a sample of people with haemophilia B in the US and measures its association with health‐related quality of life (HRQoL). Data on 135 participants aged 5–64 years were abstracted from Hemophilia Utilization Group Study Part Vb. The International Physical Activity Questionnaire assessed physical activity among participants aged 15–64 years, and the Children's Physical Activity Questionnaire abstracted from the Canadian Community Health Survey was used for participants aged 5–14 years. SF‐12 was used to measure HRQoL and the EuroQol (EQ‐5D‐3L) was used to measure health status for participants older than 18 years of age. PedsQL was used to measure HRQoL in children aged 5–18 years. Sixty‐two percent of participants in the 15–64 year‐old age cohort reported a high level of physical activity, 29% reported moderate activity and 9% reported low activity. For children aged 5–14 years, 79% reported participating in physical activity for at least 4 days over a typical week. Based on the 2008 Physical Activity Guidelines for Americans, 79% of adults achieved the recommended physical activity level. Multivariable regression models indicated that adults who engaged in a high level of physical activity reported EQ‐5D Visual Analogue Scale (VAS) scores that were 11.7 (P = 0.0726) points greater than those who engaged in moderate/low activity, indicating better health outcomes. Among children, no statistically significant differences in health outcomes were found between high and moderate or low activity groups.     

Prevalence of chronic kidney disease and associated factors among the Chinese population in Taian,China

Background

This study was designed to assess the prevalence of chronic kidney disease (CKD) and associated risk factors among the Chinese population in Taian, China.

Methods

A primary care-based cross-sectional study was conducted in Taian, China, from September to December 2012. Participants selected by a multi-stage stratified cluster sampling procedure were interviewed and tested for hematuria, albuminuria, estimated glomerular filtration rate (eGFR) and other clinical indices. Factors associated with CKD were analyzed by univariate and multivariate logistic regression analysis.

Results

A total of 14,399 subjects were enrolled in this study. The rates of hematuria, albuminuria and reduced eGFR were 4.20%, 5.25% and 1.89%, respectively. Approximately 9.49% (95% CI: 8.93%–10.85%) of the participants had at least one indicator of CKD, with an awareness of 1.4%. Univariate analyses showed that greater age, body mass index, and systolic and diastolic blood pressure; higher levels of serum creatinine, uric acid, fasting blood glucose, triglycerides, total cholesterol and low-density lipoprotein cholesterol; and lower eGFR were associated with CKD (p?<?0.05 each). Multivariate analysis showed that age, female gender, educational level, smoking habits, systolic blood pressure, and history of diabetes mellitus, hyperlipidemia, hypercholesterolemia and hyperuricemia were independent risk factors for CKD.

Conclusions

The prevalence of CKD in the primary care population of Taian, China, is high, although awareness is quite low. Health education and policies to prevent CKD are urgently needed among this population.

     

How Can I Manage Thrombocytopenia in Hemodialysis Patient? A Review

Hemodialysis (HD) is the most important treatment for patients with end‐stage renal disease (ESRD). Thrombocytopenia is a potential treatment complication related to dialysis. Under normal circumstances, the platelet count would slightly decrease within the first hour of HD, but get restored towards the end of procedure. In most patients, the platelet count can be maintained within the normal range, and the occurrence of thrombocytopenia is relatively rare in clinical practice. Therefore, the possibility of thrombocytopenia in HD patients is often ignored. Moreover, thrombocytopenia might be misdiagnosed and mistreated. At present, almost all articles on the subject, apart from some case reports, focus on pseudothrombocytopenia and heparin‐induced thrombocytopenia. In this review, we summarized various underlying causes, mechanisms, and diagnostic approaches to thrombocytopenia in HD patients. The review aims to provide a guide for clinicians interested in the causes and adequate treatment of thrombocytopenia.     

DhhP,a Cyclic di-AMP Phosphodiesterase of Borrelia burgdorferi,Is Essential for Cell Growth and Virulence

Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. Most of work on c-di-AMP signaling has been done in Gram-positive bacteria, firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect potassium transport, cell wall structure, and antibiotic resistance. Little is known about c-di-AMP signaling in other bacteria. Borrelia burgdorferi, the causative agent of Lyme disease, is a spirochete that has a Gram-negative dual membrane. In this study, we demonstrated that B. burgdorferi BB0619, a DHH-DHHA1 domain protein (herein designated DhhP), functions as c-di-AMP phosphodiesterase. Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn²⁺- or Mg²⁺-dependent manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP appears to be essential for B. burgdorferi growth both in vitro and in the mammalian host. Inactivation of the chromosomal dhhP gene could be achieved only in the presence of a plasmid-encoded inducible dhhP gene. The conditional dhhP mutant had a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Unlike what has been observed in Gram-positive bacteria, elevated cellular c-di-AMP in B. burgdorferi did not result in an increased resistance to β-lactamase antibiotics, suggesting that c-di-AMP''s functions in spirochetes differ from those in Gram-positive bacteria. In addition, the dhhP mutant was defective in induction of the σ^S factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers an important role of c-di-AMP in B. burgdorferi virulence.     

Spacer layer design for efficient fully printable mesoscopic perovskite solar cells

The spacer layer is a key component of fully printable mesoscopic perovskite solar cells, but its precise characteristics are far from being understood in relation to the device design. In the present work, we perform a detailed systematic study on the effects of spacer parameters, such as size of building blocks, layer thickness, etc., on properties of the perovskite filler, insulating ability and performance of fully printable mesoscopic perovskite solar cells by combining the techniques of time-resolved photoluminescence, high-resolution TEM, insulating resistance measurements, impedance spectroscopy and J–V characteristics. Drawing on the deep understanding from these studies, we formulate key principles, which are anticipated to guide the design of the advanced spacer layer for fully printable mesoscopic perovskite solar cells.

Key principles and reasonable routes are proposed to advance the spacer layer design for fully printable mesoscopic perovskite solar cells.

Lead halide perovskite (PVSK) as a promising semiconducting material has been introduced as a light harvesting semiconductor because of its ease of fabrication and excellent physical properties, such as tunable bandgap, strong absorbance, long carrier diffusion length and shallow intrinsic trap state level.^1–9 Extremely flat and compact perovskite thin film with large crystal size has gained particular attention to boost power conversion efficiency (PCE) by sequential deposition method, vapor deposition, solvent-annealing, solvent engineering, hot-casting method, intramolecular exchange methods, and additive, etc.^10–16 Benefiting from rapid improvements in formation of high quality perovskite thin film, a certified PCE of 25.2% has been achieved.¹⁷ However, illumination stability in real environment still remains a serious challenge due to the inherent moisture and UV sensitivity of perovskite. Moreover, using expensive and rare metals as back contact, such as gold and silver, may limit large-scale production in the future. As the competing architecture of perovskite solar cells, TiO₂/spacer/carbon (abbreviated as TSC) films based fully printable mesoscopic perovskite solar cells (FP-MPSC) have attracted a lot of researchers due to their low cost and printable large-scale production process.^18–21 In this type of solar cell, carbon can efficiently collect hole from perovskite layer even without any other hole transporting materials.^22,23 Most importantly, FP-MPSC could work with excellent illumination stability and heat-stress stability by filling TSC films with (5-AVA)_xMA_1−xPbI₃ (5-AVA = 5-aminovaleric acid, MA = methylammonium), although the efficiency of 12.8% is still far behind from the most efficient solar cell.^16,21,24Spacer, as an important part of FP-MPSC, plays a crucial role in obtaining high performance device. Basically, the spacer layer mainly burdens triple important tasks in the efficient mesoscopic perovskite solar cells. Firstly, the core function of spacer is to separate anode and cathode and to prevent electrons in TiO₂ from transporting directly to carbon electrode. The separating property of spacer depends on spacer particle sizes, morphology, materials, etc. This requires that spacer layer has no cracking and has wide bandgap. Secondly, the perovskite confined in the mesopores of spacer layer can absorb photons transmitted through perovskite/TiO₂ composite layer and have contribution to photocurrents. Thirdly, the holes produced in the perovskite/TiO₂ composite layer have to go through perovskite/spacer composite layer to reach carbon electrode. And the electrons produced in the perovskite/spacer composite layer have to go through perovskite/spacer composite layer to reach TiO₂ electrode. Because spacer layer has these important functions, some research on spacer layer have been carried out. Recently, Al₂O₃ or ZrO₂ spacer layer was compared with respect to their pore size.²⁵ However, conclusion of the effect of pore size in two different materials was incomplete. The effect of spacer layer thickness was simply discussed both in monolithic dye-sensitized solar cells and FP-MPSC.^20,26 The morphology of spacer layer was also improved to increase PCE of FP-MPSC.²⁷ Although these researches made some progress, there are no clear standards that what should an ideal spacer layer satisfy. Therefore, it is urgent to carry out detailed study on how the parameters of spacer affect the above functions and performance of mesoscopic printable perovskite solar cells.In the present study, the effects of size of building blocks of spacer layer, thickness of spacer layer on property of perovskite crystals, insulating property, and performance of mesoscopic perovskite solar cells were investigated in details. Based on these deep understandings, critical principles to design advanced spacer layer are proposed.ZrO₂ is used as spacer material due to its large band gap and high conduction band energy level. There are five different sizes of spacer building blocks in this study. The average particle sizes of spacer are measured to be about 5 nm, 10 nm, 20 nm, 60 nm and 100 nm, respectively, and hereafter referred to as S5, S10, S20, S60, S100 spacer, respectively. SEM images of as-prepared spacer films using these building blocks are shown in Fig. 1. X-ray diffraction patterns of spacer film with different particle sizes are presented in Fig. 1f, indicating that the five spacer films were all tetragonal crystal phase as majority phase. From Scherrer equation, the crystal sizes of spacer building blocks were calculated to be about 5 nm, 10 nm, 20 nm, 30 nm, 30 nm, respectively. These results indicated that the S60 and S100 particles are consisted of 30 nm sized crystal ZrO₂. Fig. 1 presents that there is a large difference in surface morphology with particle size increasing. There are cracks in S5 and S10 spacer films and micrometer scale pores exist in the S100 spacer, while the surface of S20 and S60 are very uniform without defects.Open in a separate windowFig. 1SEM images of spacer films with particle size of 5 nm (a), 10 nm (b), 20 nm (c), 60 nm (d) and 100 nm (e), respectively. (f) XRD patterns of spacer film with different building block sizes.During solvent evaporation of perovskite precursor, perovskite crystal growth is restricted by randomly interconnected mesopores of spacer film, leading to nanoscale crystal size and random crystal orientation, as observed by high resolution transmission electron microscope (Fig. 2a), in which clear crystal lattices of perovskite crystals can be distinguished from spacer particles. Meanwhile, the mesopores of spacer film is fulfilled with perovskite materials, providing continuous channels for charge carriers. The crystal size of perovskite material in spacer film is strongly influenced by mesopore size of spacer layer, as seen in XRD intensity of perovskite at 2θ of about 14.2° (Fig. 2b). There is an apparent trend that the intensity increased with increasing the particle size of spacer film. As a reference, perovskite was also deposited on bare glass, which exhibited the best crystallinity. The calculated sizes of perovskite from XRD spectra are 4.3 nm, 3.9 nm, 6.2 nm, 11.5 nm, and 12.6 nm, respectively, for the S5, S10, S20, S60, and S100 spacer layer. Apparently, the sizes of perovskite crystals confined in the spacer layer are smaller than the average pore sizes of spacer layer measured by N₂ absorption/desorption isotherms (Table S1^†). The high-resolution TEM image also gives consistent results. For example, the sizes of perovskite crystals confined in the S20 spacer layer are between 8.4 nm to 12.7 nm measured in the TEM image (Fig. 2a). The infiltrated perovskite started to nucleate onto the heterogeneous surface of spacer building blocks with high surface area, resulting to multiple nucleation centers and small crystal size. In order to evaluate the effect of spacer particle size on physiochemical properties of perovskite, the band-edge emission spectra of perovskite/spacer composite film were measured in Fig. 2c. The band-edge emission spectrum of perovskite deposited on bare glass peaked at 762 nm (with photon energy of 1.627 eV). As the particle size of spacer film decreased, a blue shift of the band-edge photoluminescence occurred, and linewidth broadened. The peak position of perovskite emission spectra can be tuned in the range of 33 nm through varying the pore size of spacer film. The increase of emission line width at grain boundaries can be attributed to disorder and defects of perovskite,^14,15 which also led to the decrease of lifetime in time-resolved PL (Fig. 2d). Perovskite film grown on glass has the lifetime of 141.9 ns. However, perovskite grown in spacer film decreased to 0.5 ns, 8.4 ns, 24.1 ns, 37.2 ns, 53.7 ns, for S5, S10, S20, S60, S100, respectively.Open in a separate windowFig. 2(a) High resolution transmission electron microscope image of perovskite/S20 spacer film composite. (b) XRD of perovskite/spacer film composite. (c) Steady PL emission spectra and (d) time-resolved PL of perovskite/spacer film composite.The particle size of spacer also has large effect on insulating ability of spacer films with the same thickness. FTO/spacer/carbon configuration was designed to measure the insulating ability of spacer layers. In ideal conditions, the resistance between carbon and FTO, defined as insulating resistance (R_I), should be infinite, indicating that there is not any leakage current from ideal insulating spacer. However, all of the measured resistance has finite values, summarized in 28–31Photovoltaic parameters of mesoscopic perovskite solar cells based on spacer with different building block sizes